The Patient Journey

Stories from cervical cancer patients and survivors, this year, about 14,480 new cases of cervical cancer will be diagnosed..

And behind very new case is a patient. With their own story.

Patient stories offer powerful insights that go beyond the statistics and outcomes, as those affected by cervical cancer have an understanding of what the journey is like. For patients diagnosed with cervical cancer and survivors, stories from others who have been through the same experience can be a source of comfort and support, and occasionally offer guidance on how to manage the experience. For spouses and family members, such stories can offer a window into the world of their loved ones. Healthcare providers also benefit from the insight offered by patients—insights they may not otherwise hear.

We are grateful that several patients and survivors have shared their stories with us, so we can pass on their insight and experiences to you. If there’s one message you can take away, it’s that— you are not alone.

patient journey cervical cancer

I received a call from my Gynecologist in March 2015 telling me I had cancer. I was so confused…she had suspected something from a “fibroid” that was growing large. She never told me she suspected cancer. All of my Paps were negative for two years prior to this.

I was overwhelmed with emotion because it was completely unexpected. Immediately I thought I was going to die after seeing my father go through colon cancer and pass away. I had been complaining for over a year about heavy bleeding, and I was told I had fibroids. After getting a scan, I had a 5 cm tumor. I couldn’t believe that my doctors had missed this for so long.

It’s been a long time since my original diagnosis but I am sure it was shock. When I’ve been diagnosed with a recurrence I feel dread. Dread for many reasons, having to tell my family and seeing their pain and dread that the treatment will be brutal. I also feel exhaustion. Figuring out what’s next in a cancer diagnosis is exhausting.

I was aware something was wrong, but cancer was so far away from my mind. Initially I was upset but within moments felt like I was hiding from the doctor behind my own hair. Like I wanted to disappear and used the only resources I had available.

It was surreal! It felt like I could be waking up from the nightmare any moment! I was given my diagnosis in the emergency room and so there was so much going on already. I don’t think that I truly was able to process that information right away. But if I had to sum up all my feelings into one word I’d say, “terrified!!”

I remember sitting at my desk at work when my doctor called with my results. Her voice began to shiver as she read to me my positive for cervical cancer results. I initially zoned out. All I could see was a black dark tunnel with muffled sound. Then I gathered myself, thanked her for the call, then called my husband. A sudden peace flooded me which allowed me to calm my emotions and racing mind.

— Tarteskikar

My initial response was disbelief. How could I, at age 33, be diagnosed with a bad Pap smear?  I had two normal vaginal births with no issues. When my youngest was four years old, I went for my annual exam. It came back as not being normal, but didn’t raise any red flags. They said come back in three months. I did, and was thrilled to have a normal Pap smear. Just to be on the safe side, my gynecologist wanted to test me again, three months later. This time, it came back much worse. I was in shock. The lab results showed that it had spread. He removed my uterus and sent it to pathology. The results showed it had an unexpected type of cancer—adenocarcinoma, a rapidly spreading cancer and is deadly. Had I not decided ahead of time to get a hysterectomy if it had spread, I might have died in just a few months. All of this took less than six months from the first abnormal Pap smear. Please! Get your Pap smears!

My initial reaction to finding out I had cancer was fear and darkness.

I initially learned of my diagnosis during my first year of medical school. It all had happened very quickly. I was shocked as I had never had any kind of abnormal Pap smear prior to this. At the time I had so many other things going on with school that I think I somewhat just buried a lot of my emotions and just kept pushing on with studying and exams and scheduled my appointments and surgery around everything with school. I don’t think I really began to see how it all impacted me until later on when I was on my clinical rotations during third and fourth year.

I was surprised of course, but immediately knew I had to put on a calm and rational front for my family. I needed to be the rock.

Guilt and shame. It took my a long time to move on from that and move towards acceptance and advocacy.

What was most helpful to you when you were first diagnosed?

What advice would you give healthcare providers about how to best support patients during their diagnosis?

First I would say that whether or not it’s caught early you still need to have some tact. I was told over the phone while driving to work. I still don’t know how I made it there. Be mindful and empathetic.

Leave room for hope. I don’t know how helpful it is to tell patients their outcome is poor before attempting treatment especially in the case of a recurrence. We know it’s going to be hard, but there is always the chance that things work out for us or at least gives us enough time to return to a pretty normal life, such as in my case. And I also understand statistically it’s not looking good, but maybe it’s time to change the conversation and keep certain dialogue in your back pocket until it’s an inevitable thing to discuss.

I would say to treat your patients as you would want and your family would want to be treated and not as a number. Empathy for your patients are vital in the care and healing process. Be open minded to not just see one side—surgery, chemo, radiation—as that takes a tremendous toll on your body and immune system. It’s important to not discourage anyone from seeking alternative treatments. It takes a lot to fight illnesses of all kinds and there are many ways outside of the box that can help people do that. All of it is just as important and plays a major part of our health and healing.

Respect for the patient as an individual

Listen to the patient. They know when something isn’t right in their body. Their input can make the difference between life and death sometimes.

Not every woman is interested in saving her uterus.  Please don’t try to talk people out of that treatment plan if they want it, even if they have not had biological children yet.

One thing that I have shared with nursing students when invited to speak to their classes is that this might be your 1000th patient with cancer but it’s this patients first time with cancer.  The things that are happening are not routine for us and just because it’s common for you, it’s scary and unnerving for us.

Be honest! Don’t hold anything back. Make sure you tell the patients all the side effects of treatment.

I would say in order to best support patients they have to be completely honest with them. No false hope or sugar coating anything. Also, I think its super important that patients know that they can select the doctor that best suits them. And not just to settle for whomever they are given if they’re not comfortable with them.

Sometimes, the patient becomes the provider...and can apply the lessons learned.

As someone who is now a fourth year medical student and will officially be an OB/GYN healthcare provider myself in the next few months when I start residency, I am definitely in a unique place. This experience has really shown me a patient’s perspective and is a huge reason why I decided to become an OB/GYN physician. I think the biggest insight I have gained from all of this is to realize that every patient has their own story, their own struggle, their own battle that is going on even outside of their medical diagnosis. Your patient might need support outside of anything medical that you can help them with. I hope to be an advocate and resource for my patients for whatever they may need, no matter what it is. I hope to be someone who is open and welcoming that my patient’s can feel comfortable with and turn to when they have questions, concerns or fears.

What has been the hardest part of your journey?

The hardest thing I have had to do on this journey is tell my children and parents that my cancer had returned.  It was harder than any treatment I have done.  To see and feel their pain is heartbreaking and there’s nothing I can do to make them feel better.

I told myself during treatment that I could do anything for a few minutes.  And, there were a LOT of “bad” moments.  But I learned to count.  And, somehow that got me through.  The treatment was the worst part.  It was awful. I had external radiation—36 rounds.  Chemo—6 treatments.  Internal radiation—I was in the hospital for a week.  A full hysterectomy.  And, many many other trips to the hospital.  I had 17 units of blood.  I had numerous infections and dehydration issues, and just on and on.  It. was. hard. But I told myself, and my primary oncologist said to me, “you will get through this.”  And, I did.

—Kathryn Jane

Being told my cancer is incurable and has returned three years after the first round of treatment was absolutely devastating. Our youngest child was about to be born through surrogacy and I knew that I wouldn’t be able to be a mother to him or my oldest son during treatment. I felt terrible that my oldest had to go through this with me again. I went through a severe depression and grieved the life I thought I’d have. Along with the devastation I experienced, it was also the hardest therapy I’d ever had and caused me to lose my hair and overall weakened my body permanently.

My fertility being put into question. Thank goodness, I was able to persevere mine through the surgery I received. Since I was 22 when I was diagnosed, it was a difficult concept to accept.

The many surgeries I’ve had after my diagnosis. It has stalled my life and any desire to make future plans, it feels like it steals my time. Starting over after every procedure. Also having to explain to my family and friends that I need yet another surgery and their disappointed faces.

The hardest part of my journey was acceptance.  I struggled with accepting that my body was weak and at times all I could do was barely open my eyes. I struggled with needing help from others when I’m the one always providing the help. It was extremely difficult for me to halt for a moment, as I’m an always-on-the-go person. I didn’t want to accept the fact that an uninvited Intruder was invading my life and all I could do was stay positive as I commanded it daily to leave.


The hardest part was the end of treatment. After going through surgery, radiation and chemo, my body and mind were toast. I had no energy and I had major pain from everything. After having a plan for every day of the week and doctors to see, it’s over and you’re left to just wait. I went to counseling and continued to work on my body and my mind. I began reading about natural medicine and working on correcting my body’s deficiencies. I changed my diet to help my body recover and continue to heal. It took about eight months to get back to somewhat normal. I began Yin Yoga as well and that was so helpful in restoring my body.

The PTSD that we live with. You may not have cancer but it sometimes feels like cancer has YOU for life. It causes anxiety and stress but day by day it differs.

Having that fear and uncontrollable uncertainty where you don’t know if you’re going to get through it or what the outcome will be is very scary. If your cancer is going to come back, that fear subsides as time passes you don’t think about it as often however each time you have follow up appointments and ultrasounds no matter how much time has passed that reality is there. I’ve not been someone who has always wanted children, however when that choice is taken away from you to have them naturally it’s a harsh reality.  It’s important to have support from as many outlets as possible, it’s vital in your healing journey.

Where are you in your journey now?

I’m on my sixth recurrence. I’m in the process of figuring out what the treatment will be for this recurrence. I recently had surgery to remove a 10cm mass from my rectum and now have an ileostomy. I’m hopeful it can be reversed soon but I’m likely facing chemo for a few months. I’m feeling good and ready to get going with treatment. I have lots of living to do!

It’s been 10 years. I have daily issues with my bladder and my colon. My legs and hips ache and aren’t very strong. But, I deal with all of it. I will not let it stop me.

I have been cancer free since may 2015, but I’ve had at least one surgery a year since. Feels never ending.

Being that I’m no longer curable, but have surpassed my less-than-two-year mark by two years so far now, I feel truly grateful for the chance to survive one more day. I was in remission for two years while being given the experimental drug once every three weeks, until it started to damage my internal organs severely and i had to stop receiving the treatments. I am scanned every three months to keep a close eye on new progression. I do however feel nervous that the only one thing that was able to keep me alive beyond the doctors expectations, has had to be discontinued…

Terminando una etapa de mi vida que jamás pensé superar pero lo hice gracias al apoyo de todos.

Translation: Finishing a stage of my life that I never thought to overcome, but I did it thanks to everyone’s support.

I am over six years out from my surgery and treatment. Sometimes, I still can’t believe I’m here. My youngest daughter just turned 16 and got her driver’s license. Things like this hit me hard and I just cry, as I’m so appreciative to be a part of life and my family. I still suffer treatment side effects such as lymphedema in my right leg and bowel issues, but for the most part I live a normal life. I work a lot less and spend as much time as I can with my family.

Today, I’m celebrating my fifth year of being cancer free!!!! I’m advocating, educating and LIVING a life of GRATITUDE!!

I am finally speaking out about what I went through, and it was so liberating.

I have always been one that has a love for traveling. However after something happens to your health personally for me it’s really opened my eyes that I have to live fully in the moment and appreciate each day as a gift. I feel that this experience has made me stronger that I could have ever imagined. It allowed me to look at my life as it’s not guaranteed and to do as much as possible with the time I am given. It encouraged me to travel as much and as often as possible over the past years. It taught me to be more appreciative and grateful for my life, and my loved ones. Seeing life from a different perspective.

What other final words of support or advice do you have for other patients diagnosed with cervical cancer?

We want to thank all of those who helped contribute to this page by sharing their personal stories with us. we are so grateful for your time and your insight..

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Woman who got cervical cancer at 24 recalls symptom she 'downplayed' before diagnosis

In 2020, Anna Ogo underwent a pap smear as part of a routine checkup. Ogo felt stunned when the results were abnormal, and soon she learned she had cervical cancer.

“I knew that disease existed,” the 35-year-old from outside Seattle tells "But I didn’t really know what it was."

Ogo grew up in Japan and never received the HPV vaccine. There's also a stigma surrounding human papillomavirus (HPV) and cervical cancer in her home country, she says.

“There’s a lot of misunderstanding around it. It’s related to sexual activities, and nobody wants to talk about it,” she says. “I felt shame and guilt.” (The vast majority of cervical cancer is caused by HPV, and HPV is the most common sexually transmitted infection, according to Columbia University Herbert Irving Comprehensive Cancer Center .)

Anna Ogo shares her story of being diagnosed and treated for cervical cancer because she wants to "everyone to take the chance to prevent this."

As a teen, Morgan Newman understood the importance of regular pap smears in screening for cervical cancer. But when she was offered the HPV vaccine as a teen, she refused.

“My mom begged and begged me to get the vaccine, but I looked at her and I said, ‘That’ll never happen to me. I will never get that cancer,’” Newman, 33, of Norwalk, Iowa, tells “Here I was eight years later, getting diagnosed with HPV-related cervical cancer.”The two women are sharing their stories to encourage people to receive the HPV vaccine and undergo regular cervical cancer screenings.

“If I could prevent someone else from making that same mistake, for thinking that this will never happen to them, (I want to),” Newman says.

Routine screening finds cancer

For both Ogo and Newman, a pap smear found their cervical cancers.

Before she was diagnosed in 2014 at age 24, Newman experienced pain and bleeding after sex that could have been an early sign of cervical cancer.

“I was in a new relationship, in the first couple of months, and things can get exciting, and you are exploring,” she says. “It was after having intercourse that I really noticed the bleeding became an issue.” 

While she felt a little concerned, she didn’t address it immediately.

“As women, we really truly downplay our symptoms, our pain because we have so much else that we’re juggling,” she says.

About a month later, Newman received a pap smear, and the test detected abnormal cells. But she'd had friends who had abnormal pap smears in the past that turned out to be nothing, so Newman didn’t worry about it. When she underwent a colposcopy — a follow-up exam that allows doctors to get a closer look at cervical cells — she experienced terrible pain.

Morgan Newman shared her experience with Dr. Linda Eckert for her book, "Enough: Because We Can Stop Cervical Cancer."

“The colposcopy was horrendous. I was hemorrhaging on the table. It was very painful,” she says. “I got referred to a gynecologic oncologist and I was 24 years old. I didn’t connect the dots.”

During the visit with the oncologist, she underwent a biopsy to test her cervical cells for cancer. Soon after, she learned what the biopsy uncovered.

“I heard the words, ‘I’m sorry, Miss Newman, but you have cervical cancer,'” she recalls. “I was absolutely surprised.”  

Doctors diagnosed Newman with stage 3 cervical cancer because it had spread to three pelvic lymph nodes.

“I was definitely in shock. I was a little bit angry,” she says, adding that she was diagnosed with cervical adenocarcinoma.

Newman underwent six weeks of chemotherapy, external radiation treatment and internal radiation, also called brachytherapy.

“That was a traumatizing event for me because of the type of devices they use,” she says. “The thing that will never leave my memory is when they nurse asked if I had children, if I had ever gone into labor. … She said that when they were removing the device it was going to feel a lot like childbirth.”

Aside from the pain, it was a stark reminder that Newman will likely never carry children due to the cancer treatment.

“I live with that memory,” she says. “That’s the closest thing I will ever have to childbirth.”

Ogo’s treatment plan differed as she had an early-stage cervical cancer and her doctors opted for a radical hysterectomy, which included removing her cervix and uterus. She kept her ovaries but treatment temporarily put her in menopause.

“After two or three months, the (ovarian) function came back,” she says. “My doctors decided I was not in menopause, which was good news.”

Ogo still experiences side effects from treatment, including pain during urination and feeling like she has a urinary tract infection when she does not. She also feels frequent abdominal pain and pelvic floor pain.

“My vagina has become tense with scar tissue,” she says. “I have to go through pelvic floor physical therapy. ” Ogo is in remission.

Following Newman’s treatment, doctors saw no evidence of disease, but at her three-month follow-up, she had spots in her lungs, meaning her cancer had returned and was stage 4. She underwent three more months of treatment and hasn't had any recurrences since.

With Newman's stage of cancer, “you’re automatically, they say, incurable,” she says. While you can go into remission, "it’s never really gone," she adds.

Cervical cancer

The cervix is the bottom of the uterus and connects the vagina to the uterus, according to the National Cancer Institute . Human papillomavirus infections that linger in one’s body cause nearly all cervical cancer, the organization notes.

“HPV is an extremely common virus that is transmitted sexually, and by the time people have had three partners, 50% will have had HPV, and 80% of adults have had HPV at some point in their lives,” Dr. Linda Eckert, an OB-GYN and author of the book “Enough: Because We Can Stop Cervical Cancer,” tells “Clearly, not everybody gets cancer.”

In many cases, people’s bodies “get rid of HPV,” but in some cases, it remains, Eckert says. “It’s only when it persists and stays around that it can cause precancerous changes.”

There are about 200 types of HPV, according to the World Health Organization , but only a dozen of then cause cancer, Eckert explains. HPV screening looks for those 12 high-risk types. The HPV vaccine protects people from five of the cancerous strains of the virus, Eckert says.

“If you can get this vaccine in your body before you get exposed to these viruses that cause cervical cancer, the vaccine is incredibly effective — almost 99% effective at preventing your body from acquiring an infection,” she says. “The primary prevention is (stopping) the infection from getting in the body in the first place.”

The U.S. Centers for Disease Control and Prevention recommend that parents vaccinate their children against HPV starting at 11 or 12 for boys and girls. The HPV is either two or three doses, depending on the age when vaccination starts. Many people don't know that the HPV vaccine can also protect boys.

“They tend to offer it to men and boys for several reasons, No. 1 is throat cancer," Eckert says noting that 60% to 70% of throat cancer is caused by HPV. HPV can also lead to penile and anal cancers.

Cervical cancer can be fatal, with most deaths occurring in developing nations. The World Health Organization estimates that 342,00 people died from it in 2020.

“(About) 90% of the cases of deaths of cervical cancer do occur in low-resource settings,” Eckert explains. “Cervical cancer tends to kill women between the ages of 35 to 50. Many of them have children.”

The World Health Organization has an ongoing initiative to eliminate cervical cancer , launched in 2020, which represents a “first,” Eckert says.

“We are feeling the burden of this cancer,” she says. “If you have a preventable cancer and you are not making it a high enough public health priority to prevent, it really is to me a statement about how we value women.”

Life after cervical cancer

Ogo and her husband welcomed a baby recently with the help of a surrogate. “That was such a blessing,” she says. “I feel very lucky.”

Life has been good, though Ogo feels anxiety before scans to check if her cancer has returned. 

After her cervical cancer diagnosis, Morgan Newman went to school to become a social worker, eventually earning a master's degree. Learning about trauma-informed care helped her process her experience, and she feels grateful she can help advocate for others in her job at Cervivor.

Newman works for Cervivor , a nonprofit that raises awareness of cervical cancer, and has two dogs. A few years ago, she climbed Mount Kilimanjaro. Both women said they wanted to share their stories so others do not experience what they did.

“I truly would never want anyone to walk through what I’ve been through and what I continue to walk through,” Newman says. “We have the tools to prevent cervical cancer.” 

Meghan Holohan is a digital health reporter for and covers patient-centered stories, women’s health, disability and rare diseases.

patient journey cervical cancer

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patient journey cervical cancer

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patient journey cervical cancer

Your toolkit for reducing cervical cancer risk

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By Nicole Brudos Ferrara

Cervical cancer is the fourth most common cancer in women globally, particularly in low- and middle-income countries. In the U.S., cervical cancer is no longer a common cause of cancer death because of the use of a screening test called a Pap smear , which detects changes in cervical cells.

While the overall rate of cervical cancer in the U.S. is declining, the number of people diagnosed with late-stage cervical cancer is increasing , and rates among Black women are disproportionately high. Research also indicates that many women still are not being screened for cervical cancer.

Kristina Butler, M.D. , a Mayo Clinic gynecologic oncologist, discusses the tools available to reduce your cervical cancer risk, including a trusted healthcare professional, the HPV vaccine and regular screening:

Tool No. 1: Find a healthcare professional you trust.

Many people in the U.S. don't have a healthcare professional they see regularly. The causes are complicated and include being underinsured, barriers related to cost and transportation, and mistrust in the healthcare system — all of which can lead to late-stage cervical cancer diagnoses and poorer outcomes.

"People need to find a care professional they're comfortable with. Catching changes in the cervix and cancers early improves long-term outcomes," says Dr. Butler.

If you don’t visit a healthcare professional regularly due to cost or lack of insurance, you may be eligible for free or low-cost screening through the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). A program of the Centers for Disease Control and Prevention (CDC), the NBCCEDP helps people with low incomes who do not have adequate insurance gain access to breast and cervical cancer screening, diagnosis and treatment. Find a screening program near you .

Your local health department or women's clinic may also provide free or low-cost options for screening. The CDC website offers lists of health departments that you can search to find resources in your area.

Dr. Butler recommends establishing a relationship with a healthcare professional you see for a checkup once a year — a primary care provider or a gynecologist, a doctor who specializes in female reproductive health. "During that visit, it’s important to discuss symptoms and anything you think may be out of the ordinary related to the genital area. That discussion might prompt the need for a pelvic exam . A person should be comfortable requesting an exam because, in many instances, it's hard to define normal."

Tool No. 2: Get the HPV vaccine for yourself and your children.

Nearly all cervical cancers are caused by HPV (human papillomavirus) infection, which can also cause cancers of the vagina , vulva , anus , penis , and head and neck . Getting vaccinated against HPV is your best protection against HPV infection and cervical cancer.

"You can receive the vaccine at age 9, and you may still get some protection if you get it up to age 45. With this vaccine, we're hoping to eradicate cervical cancer and other HPV-related cancers," says Dr. Butler.

The CDC   recommends the HPV vaccine for children aged 11 and those under age 26 who were not vaccinated. People younger than 15 can be vaccinated with two doses, six to 12 months apart. People who start the vaccine series later, after age 15, should get three vaccine doses over six months.

Adults 27 to 45  who were not vaccinated should talk to their healthcare professional about the HPV vaccine. Dr. Butler says the vaccine can provide benefits even after you have been diagnosed with changes to cells in your cervix that make them more likely to develop into cancer or you have been exposed to HPV.

"The HPV vaccine is exciting because it gives us an opportunity to prevent cancer," says Dr. Butler. “We can reduce the risk of several cancers with this vaccine."

Tool No. 3: Start cervical cancer screening at age 21 and follow a schedule.

"At Mayo Clinic, we recommend that cervical cancer screening start at age 21 and continue every three to five years, depending on the type of screening performed," says Dr. Butler. "At the time of screening, we do a thorough examination to evaluate multiple areas. We are looking at the vulva, the vagina, the urethral area and the anal area for anything unusual."

In addition to a pelvic exam , your healthcare professional will conduct a Pap smear , which involves collecting cells from your cervix to detect any changes. Mayo Clinic recommends repeating Pap testing every three years for women ages 21 to 65.

Dr. Butler says you should continue screening following menopause , particularly if you have any bleeding. "At 65, if you have had normal screening test results for quite some time, you can have a discussion with your healthcare professional about discontinuing," she says. "But we know that 16% of cervical cancer happens in women over the age of 65."

Women age 30 or older can consider Pap testing every five years if the procedure is combined with an HPV test . Knowing whether you have a type of HPV that puts you at high risk of cervical cancer allows you and your care team to decide on the next steps, which may include monitoring or further testing.

Your healthcare professional may recommend a different screening schedule depending on your risk factors and history of screening results. "A patient may have high-risk factors that require more frequent screening. Examples include people with weakened immune systems or people with a history of cervical dysplasia ," says Dr. Butler. "Following hysterectomy, most people no longer need cervical cancer screening. But if they have high-risk factors, they should speak to their doctor because they might need screening with a Pap smear that can be performed in the vaginal area since there is no longer a cervix."

If you've been diagnosed with cervical cancer, Dr. Butler says new treatments are giving more people hope.

"For people with advanced and recurrent cervical cancer, we use chemotherapy and a targeted therapy drug called bevacizumab , which works by blocking a protein called VEGF," she says. "For some people whose cancer has markers for the protein PD-L1, we're able to use pembrolizumab — an immunotherapy drug called an immune checkpoint inhibitor ." Pembrolizumab works by binding to the protein PD-1 on the surface of T cells (a type of immune cell). This prevents the cancer cells from weakening the immune system, which can then kill the cancer cells.

"The development of these additional drugs has absolutely improved outcomes," says Dr. Butler.

Learn more about cervical cancer and find a clinical trial at Mayo Clinic.

Join the Gynecologic Cancers Support Group on Mayo Clinic Connect, an online community for patients and caregivers.

Also, read these articles:

  • " Cervical Cancer FAQ "
  • " HPV vaccine: Who needs it, how it works "
  • " Cervical cancer and HPV — what’s the connection? "
  • " Mayo Clinic Minute: Cervical Cancer Screening "
  • " Protecting kids from cancer with HPV vaccine "
  • " Dangers of late cervical cancer diagnosis in women of color "

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Am Fam Physician. 2018;97(7):449-454

Related article : Cervical Cancer Screening

Author disclosure: No relevant financial affiliations.

Human papillomavirus infection is the precursor for the development of cervical cancer and is detectable in 99.7% of squamous cell carcinoma and adenocarcinoma cases. Early detection of precancerous lesions with Papanicolaou testing remains the primary mechanism for cancer prevention. Once cervical cancer is diagnosed, treatment may involve surgery, radiation therapy, chemotherapy, or a combination. The choice of therapy depends on the stage of disease, lymph node involvement, patient comorbidities, and risk factors for recurrence. Early-stage, microinvasive disease may be treated with surgery alone if margins are negative and there is no lymph node involvement; adjuvant chemoradiation should be considered for other early-stage disease. Locally advanced disease is often treated with chemoradiation. The addition of bevacizumab, an antivascular endothelial growth factor monoclonal antibody, to combination chemotherapy improves survival among patients with recurrent, persistent, or metastatic cervical cancer. Disease stage and lymph node involvement are the most prognostic factors. Pregnancy status and desire to preserve fertility should be considered when developing a treatment strategy. After treatment, close follow-up with a gynecologist-oncologist for pelvic examinations at regular intervals is recommended to assess for recurrence.

Every year, nearly 13,000 cases of cervical cancer are diagnosed, with more than 4,000 deaths. 1 Although the highest incidence of cervical cancer is among women 40 to 49 years of age (14 cases per 100,000 women per year), 40% of women are older than 40 years at diagnosis. 2 Rates of cervical cancer are higher in the southern region of the United States. 2 There are significant disparities in cervical cancer–related mortality among racial and ethnic groups. Black women are more than twice as likely to die from cervical cancer than white women. 3 Mortality rates are also higher among Hispanic women. 1

Human papillomavirus (HPV) infection is the precursor for the development of cervical cancer. 4 Early detection of precancerous lesions with Papanicolaou (Pap) testing is the primary mechanism for cancer prevention. 5


HPV is detected in 99.7% of squamous cell carcinomas and adenocarcinomas, 6 the most common types of cervical cancer ( Table 1 ) . 4 There are 15 known oncogenic strains of HPV, with types 16 and 18 involved in 70% of cervical cancer cases. 7 Most sexually active adults will be exposed to HPV, and more than 50% of adults 20 to 24 years of age are currently infected. 8 However, the immune system clears the virus within six months in 50% of women with the infection and within two years in up to 90% of women. 9 , 10

When HPV infection persists in the metaplastic epithelium of the cervical transformation zone, it can lead to dysplastic cellular changes. Although low-grade dysplasia (cervical intraepithelial neoplasia 1 [CIN1]) usually regresses, it can progress to high-grade dysplasia (CIN2 or CIN3). 11 Cervical cancer occurs when high-grade lesions extend beyond the basement membrane of the cervical epithelium. Approximately 20% of women with high-grade dysplasia will develop invasive cervical cancer within five years if left untreated. 12

Risk Factors

Most cervical cancer risk factors relate to increased exposure to HPV or decreased ability to clear the virus immunologically. 13 Smoking is associated with an increased risk of squamous cell carcinoma but not adenocarcinoma. This risk decreases by one-half 10 years after smoking cessation. 14 Evidence suggests a genetic susceptibility to cervical cancer, and several genetic alterations have been implicated. 15

In addition, a large prospective cohort study found that use of oral contraceptives for five to nine years was associated with increased risk of cervical cancer (hazard ratio = 2.0; 95% confidence interval, 1.3 to 3.0). The mechanism appears to be hormonal rather than behavioral and may be due to the effect of sex steroids on oncogene expression. 16 The risk appears to decline after cessation of oral contraceptives. However, CIN is not currently a contraindication to oral contraceptive use per the U.S. Medical Eligibility Criteria or cervical cancer treatment guidelines. 17 Table 2 includes risk factors for cervical squamous cell carcinoma. 1 , 13 – 16 , 18 , 19

Cervical cancer may be detected after a Pap test result is abnormal, a lesion is visualized on pelvic examination, or clinical symptoms develop. Management of abnormal Pap test results should follow the American Society for Colposcopy and Cervical Pathology guideline. 20 If colposcopy is indicated because of an abnormal Pap test result or visible lesion, cervical cancer may be diagnosed by colposcopy-directed biopsy or by an excisional procedure.

Although early cervical cancer is usually asymptomatic, it may cause abnormal uterine bleeding or postcoital bleeding. Advanced lesions can cause bladder outlet obstruction, resulting in bladder or bowel symptoms, back or pelvic pain, hematuria, or renal failure. On pelvic examination, cervical cancer may manifest as superficial ulceration, an exophytic tumor, or an enlarged, indurated cer vix. Any abnormal lesion visible on the cervix should be biopsied regardless of cervical cytology. Adenocarcinomas may not lead to an identifiable lesion if located in the endocervical canal.

Cervical cancer spreads via direct extension, and lymphatic and hematogenous routes. Staging is determined using the International Federation of Gynecology and Obstetrics 2014 guideline ( Table 3 ) . 21 , 22 Cervical cancer is the only gynecologic cancer staged clinically before surgery, based on tumor size, depth of invasion, spread into surrounding tissue, and distant metastases (usually lung, liver, and bone). 21 In suspected microinvasive disease, conization is used to determine depth of invasion.

Additional diagnostic studies may aid in determining spread and prognosis, and in planning treatment. Computed tomography or magnetic resonance imaging assesses tumor size and spread, and computed tomography with or without positron emission tomography is used to evaluate lymphovascular space invasion (LVSI).

Management of cervical cancer depends on stage, lymph node involvement, patient comorbidities, and risk factors for recurrence. 23 Treatment may include surgical resection, radiation, chemotherapy, or a combination. There are several types of hysterectomy procedures that are used to treat cervical cancer depending on stage ( Table 4 ) , and a minimally invasive approach (laparoscopic or robotic) is often possible. 24 Microinvasive disease (stage IA1) and no LVSI may be treated with simple hysterectomy if margins are negative. 25 Women with early disease (stage IA–IB1) may be treated with radical hysterectomy and pelvic lymphadenectomy. A 2016 Cochrane review of 401 women with early disease (stage IA2–IIA) and risk factors for recurrence found that after surgery, adjuvant platinum-based chemoradiation significantly reduced mortality compared with radiation alone (hazard ratio = 0.56; 95% confidence interval, 0.36 to 0.87). 26 Women who are not surgical candidates may be treated with primary radiation therapy or chemoradiation.

Locally advanced cervical cancer is often treated with primary chemoradiation. 27 Currently, treatment is based on combination therapy with platinum-based regimens. Radiation involves external beam and high-dose intracavity brachytherapy. 28 Posttreatment hysterectomy is not associated with increased survival rates and therefore is generally not recommended. 29 However, hysterectomy may be performed in patients who have large, bulky tumors or high posttreatment tumor volumes.

Treatment of recurrent disease includes medical or surgical options. For women with local recurrence, surgical resection with hysterectomy or pelvic exenteration is an option. Exenteration is an ultraradical surgical procedure that involves en bloc removal of female reproductive organs, the lower urinary tract, and a portion of the rectosigmoid. Exenteration is generally used for women who have had previous unsuccessful radiation treatment, with or without hysterectomy, and it has a 50% cure rate. 30 However, the procedure has a 3% to 5% mortality rate, 50% of patients have major complications, and there are no controlled trials to evaluate its effectiveness. 31

Women with advanced metastatic disease are treated with chemotherapy (and radiation if not previously offered). Bevacizumab (Avastin) is an antivascular endothelial growth factor monoclonal antibody that inhibits tumor angiogenesis. A 2017 double-blind, randomized trial of 452 patients with recurrent, persistent, or metastatic cervical cancer found that adding bevacizumab to combination chemotherapy was associated with a 23% improvement in overall survival (hazard ratio = 0.77; 95% confidence interval, 0.62 to 0.95; P = .007) and an extension of median overall survival from 13.3 months to 16.8 months compared with combination chemotherapy alone. This trial confirms persisting benefit of bevacizumab that was previously shown in an interim survival analysis. 32

Physicians should consider referring patients to regional cancer centers. A 2012 Cochrane review found that women with gynecologic cancer had prolonged survival when treated at facilities with centralization of services, such as regional cancer centers or academic institutions, compared with women treated at community hospitals. 33

Prognosis is impacted by stage, tumor volume, depth of cervical stromal invasion, metastases, and LVSI ( Table 3 21 , 22 ) . Disease stage and lymph node status are the two most prognostic factors. For example, women with stage IA disease have a 93% five-year survival rate, 22 but LVSI reduces this by approximately 50%. 34


The incidence of adenocarcinoma has increased by 35% over the past 35 years. 4 Although risk factors, diagnosis, staging, and treatment of adenocarcinoma are generally the same as for squamous cell carcinoma, there are some additional considerations. Ovarian metastases are more common with adenocarcinoma, and thus oophorectomy is recommended in early-stage disease. 35 Larger adenocarcinomas (greater than 2 cm) are more likely to involve lymph nodes and have higher recurrence rates compared with squamous cell carcinomas of the same size. 36

Fertility Preservation

Fertility-sparing options are available for women with early-stage cervical cancer. Stage IA1 can be treated with conization if margins are negative. More advanced disease can be treated with radical trachelectomy (removal of the cervix) and pelvic lymph node dissection. Fertility-sparing treatments for disease beyond stage IB1 and greater than 2 cm are not recommended. 25 Women should be counseled regarding future pregnancy risk, including preterm birth, and need for obstetric consultation.

Colposcopy without endocervical curettage is safe during pregnancy and preferred at 20 weeks' gestation if indicated based on the American Society for Colposcopy and Cervical Pathology guideline for managing an abnormal Pap test result. 37 Stage IA1 disease may be treated with conization. 25 In women with more advanced disease, management should be individualized based on stage, gestational age, and desire for continuation of the pregnancy. Imaging for staging should consider risk of fetal exposure to radiation and contrast media, and the value of diagnostic accuracy of the test compared with potentially safer studies.

Recurrence of cervical cancer occurs locoregionally or as metastatic disease, usually within three years of treatment. 38 Therefore, initial close follow-up with a gynecologist-oncologist for pelvic examinations at regular three- to six-month intervals is recommended for the first two to five years following treatment, depending on risk of recurrence. Women with local recurrence may present with vaginal discharge, vaginal bleeding, dyspareunia, or pelvic pain. On physical examination, physicians may palpate or visualize a mass at the vaginal cuff. Metastatic symptoms may be vague or related to the affected site, such as bone pain. Imaging is not recommended unless otherwise indicated based on symptoms or physical examination findings.

After regular follow-up with a gynecologist-oncologist, low-risk women with early-stage disease may resume care with their primary care physicians after two to three years. Annual cytology is performed for detection of lower genital tract dysplasia, which occurs more often in women with a history of cervical cancer. 39 Cervical cancer survivors should receive annual pelvic examinations to monitor for local recurrence and radiation-induced pelvic cancer. 38 , 40

Patient Counseling

Patients should be educated about symptoms of potential recurrence and adverse effects of cervical cancer treatments ( Table 5 ) . Patients undergoing treatment may struggle with sexual, bowel, and urinary dysfunction, especially after radiation. 27 Women with ovarian failure may be treated with hormone therapy; however, there is limited evidence of its safety in cervical cancer survivors.

This article updates a previous article on this topic by Canavan and Doshi . 41

Data Sources: General searches were done using Essential Evidence Plus, UpToDate, DynaMed, the U.S. Preventive Services Task Force website, and the Cochrane database. The American Society for Colposcopy and Cervical Pathology, Journal of Lower Genital Tract Disease , and Obstetrics and Gynecology websites were also searched for disease-specific information and guidelines. A PubMed search was completed in Clinical Queries using the key terms cervical cancer, fertility, pregnancy, and human papillomavirus. Search dates: January 5 through November 10, 2017.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5-29.

Viens LJ, Henley SJ, Watson M, et al. Human papillomavirus-associated cancers—United States, 2008–2012. MMWR Morb Mortal Wkly Rep. 2016;65(26):661-666.

Beavis AL, Gravitt PE, Rositch AF. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017;123(6):1044-1050.

Adegoke O, Kulasingam S, Virnig B. Cervical cancer trends in the United States: a 35-year population-based analysis. J Womens Health (Larchmt). 2012;21(10):1031-1037.

Subramaniam A, Fauci JM, Schneider KE, et al. Invasive cervical cancer and screening: what are the rates of unscreened and underscreened women in the modern era?. J Low Genit Tract Dis. 2011;15(2):110-113.

Böhmer G, van den Brule AJ, Brummer O, Meijer CL, Petry KU. No confirmed case of human papillomavirus DNA-negative cervical intraepithelial neoplasia grade 3 or invasive primary cancer of the uterine cervix among 511 patients. Am J Obstet Gynecol. 2003;189(1):118-120.

Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: variation by geographical region, histological type and year of publication. Int J Cancer. 2011;128(4):927-935.

Satterwhite CL, Torrone E, Meites E, et al. Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008. Sex Transm Dis. 2013;40(3):187-193.

Rodríguez AC, Schiffman M, Herrero R, et al.; Proyecto Epidemiológico Guanacaste Group. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst. 2008;100(7):513-517.

Plummer M, Schiffman M, Castle PE, Maucort-Boulch D, Wheeler CM ALTS Group. A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis. 2007;195(11):1582-1589.

Campos NG, Burger EA, Sy S, et al. An updated natural history model of cervical cancer: derivation of model parameters. Am J Epidemiol. 2014;180(5):545-555.

McCredie MR, Sharples KJ, Paul C, et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008;9(5):425-434.

International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies [published correction appears in Int J Cancer . 2007;120(11):2525]. Int J Cancer. 2007;120(4):885-891.

Roura E, Castellsagué X, Pawlita M, et al. Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort. Int J Cancer. 2014;135(2):453-466.

Hemminki K, Chen B. Familial risks for cervical tumors in full and half siblings: etiologic apportioning. Cancer Epidemiol Biomarkers Prev. 2006;15(7):1413-1414.

Roura E, Travier N, Waterboer T, et al. The influence of hormonal factors on the risk of developing cervical cancer and pre-cancer: results from the EPIC Cohort [published correction appears in PLoS One . 2016;11(3):e0151427]. PLoS One. 2016;11(1):e0147029.

Centers for Disease Control and Prevention. Summary chart of U.S. Medical Eligibility Criteria for contraceptive use. . Accessed November 14, 2017.

Wallin KL, Wiklund F, Luostarinen T, et al. A population-based prospective study of Chlamydia trachomatis infection and cervical carcinoma. Int J Cancer. 2002;101(4):371-374.

Singh GK, Miller BA, Hankey BF, Edwards BK. Area socioeconomic variations in U.S. cancer incidence, mortality, stage, treatment, and survival, 1975–1999. . Accessed November 14, 2017.

Massad LS, Einstein MH, Huh WK, et al.; 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors [published correction appears in J Low Genit Tract Dis . 2013;17(3):367]. J Low Genit Tract Dis. 2013;17(5 suppl 1):S1-S27.

FIGO Committee on Gynecologic Oncology. FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. Int J Gynaecol Obstet. 2014;125(2):97-98.

AJCC Cancer Staging Manual . 7th ed. New York, NY: Springer; 2010.

National Comprehensive Cancer Network. Cervical cancer. October 10, 2016. [registration required]. Accessed January 28, 2017.

Marin F, Plesca M, Bordea CI, Moga MA, Blidaru A. Types of radical hysterectomies: from Thoma Ionescu and Wertheim to present day. J Med Life. 2014;7(2):172-176.

Chuang LT, Temin S, Berek JS. Management and care of women with invasive cervical cancer: American Society of Clinical Oncology resource-stratified clinical practice guideline summary. J Oncol Pract. 2016;12(7):693-696.

Falcetta FS, Medeiros LR, Edelweiss MI, Pohlmann PR, Stein AT, Rosa DD. Adjuvant platinum-based chemotherapy for early stage cervical cancer. Cochrane Database Syst Rev. 2016(11):CD005342.

Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: individual patient data meta-analysis. Cochrane Database Syst Rev. 2010(1):CD008285.

Liu R, Wang X, Tian JH, et al. High dose rate versus low dose rate intracavity brachytherapy for locally advanced uterine cervix cancer. Cochrane Database Syst Rev. 2014(10):CD007563.

Kokka F, Bryant A, Brockbank E, Powell M, Oram D. Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer. Cochrane Database Syst Rev. 2015(4):CD010260.

Berek JS, Howe C, Lagasse LD, Hacker NF. Pelvic exenteration for recurrent gynecologic malignancy: survival and morbidity analysis of the 45-year experience at UCLA. Gynecol Oncol. 2005;99(1):153-159.

Höckel M, Dornhöfer N. Pelvic exenteration for gynaecological tumours: achievements and unanswered questions. Lancet Oncol. 2006;7(10):837-847.

Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017;390(10103):1654-1663.

Woo YL, Kyrgiou M, Bryant A, Everett T, Dickinson HO. Centralisation of services for gynaecological cancers. Cochrane Database Syst Rev. 2012(3):CD007945.

Gien LT, Covens A. Lymph node assessment in cervical cancer: prognostic and therapeutic implications. J Surg Oncol. 2009;99(4):242-247.

Shimada M, Kigawa J, Nishimura R, et al. Ovarian metastasis in carcinoma of the uterine cervix. Gynecol Oncol. 2006;101(2):234-237.

Lee KB, Lee JM, Park CY, Lee KB, Cho HY, Ha SY. What is the difference between squamous cell carcinoma and adenocarcinoma of the cervix? A matched case-control study. Int J Gynecol Cancer. 2006;16(4):1569-1573.

Saslow D, Solomon D, Lawson HW, et al.; ACS-ASCCP-ASCP Cervical Cancer Guideline Committee. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin. 2012;62(3):147-172.

Elit L, Fyles AW, Devries MC, Oliver TK, Fung-Kee-Fung M Gynecology Cancer Disease Site Group. Follow-up for women after treatment for cervical cancer: a systematic review. Gynecol Oncol. 2009;114(3):528-535.

Li Z, Barron S, Hong W, Karunamurthy A, Zhao C. Surveillance for recurrent cancers and vaginal epithelial lesions in patients with invasive cervical cancer after hysterectomy: are vaginal cytology and high-risk human papillomavirus testing useful?. Am J Clin Pathol. 2013;140(5):708-714.

Salani R, Backes FJ, Fung MF, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol. 2011;204(6):466-478.

Canavan TP, Doshi NR. Cervical cancer. Am Fam Physician. 2000;61(5):1369-1376.

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3 life-extending care advancements for women with cervical cancer

Female patient speaking with care provider.

Thousands of Americans will be diagnosed with cervical cancer this year, most of which will likely be between 35 and 44 years old, according to American Cancer Society estimates. Advances in cervical cancer care are prolonging survivorship for these young women — daughters, sisters, wives, aunts, and mothers — with much more of their lives to live, says Nolan J. Kinne, MD , a gynecologic oncologist at Loma Linda University Cancer Center .

For January’s Cervical Health Awareness Month, Kinne outlines three top care advancements that can improve outcomes for patients with cervical cancer .

“Having viable options that we can offer patients to feel better and extend their life in a meaningful way is a very powerful aspect of my work,” he says.

Radical hysterectomy

In recent years, Kinne says cancer experts have adjusted their surgical approaches to radical hysterectomy — an operation to treat early-stage cervical cancer — based on new evidence. Results from a large clinical trial showed that women with early-stage cervical cancer who underwent traditional open surgery experienced better outcomes than those who underwent minimally invasive surgery. Women who’d undergone minimally invasive surgery, including robotic surgery, were more likely to have their cancer come back or recur than those who had open surgery and were less likely to be alive three years after their surgery.

In other words, while the minimally invasive approach eases patients' recovery process, Kinne says open surgery offers the advantages of less likely recurrence and prolonged overall survival.

“In the rest of the surgical field, we generally see trends toward minimally invasive approaches, whereas, with the cervix, we are headed in the reverse direction based on proof that this method is more effective in treating cancer,” he says.


While cervical cancer that has progressed to an advanced stage is no longer curable and cannot be surgically removed, Kinne says other treatment options are extending patients’ lives. New classes of medicines called immunotherapy are emerging and opening new doors for patients. In recent years, immunotherapy drugs called immune checkpoint inhibitors (PD-1 inhibitors) have helped treat many types of advanced cancer, including cervical.

These medicines can pair with chemotherapy to combat cervical cancer that is not shrinking with current treatment, has recurred, or has spread to distant sites. Patients may also opt for immunotherapy alone if their cervical cancer has recurred or spread during or after chemotherapy treatment.

Antibody-drug conjugates

Another emerging class of medicine called antibody-drug conjugates is showing promising results in treating women with cervical cancer. A recent clinical trial has shown the effects of one such drug called tisotumab vedotin-tftv in helping women with recurrent cancers (cancer that has come back despite treatment). Kinne says the tisotumab vedotin-tftv attaches to cervical cancer cells and, once inside the cell, releases chemotherapy’s toxic effects to kill the cancerous cell. The medication has raised the response rate — the proportion of patients who have a partial or complete response to therapy — from 20% with traditional treatments to 40% on tisotumab vedotin-tftv.

Kinne says patients with recurrent cervical cancer didn't have any good options in the past, but this medicine provides a potential option for second-line therapy.

“Cervical cancer, especially at advanced stages, is a challenging disease to treat and manage,” Kinne says. “We are continuing to work on improving cervical cancer care to prolong and improve patients’ lives, but in reality, we have the means to avoid this situation altogether as a population.”

Read : Obstetrician-gynecologist discusses ways to lower risk or catch cervical cancer early

Prevention and early detection are vital, says Kinne — the best way to overcome and cure cervical cancer. With the prevention and screening tools at our disposal, women could avoid advanced cervical cancer entirely.

Experts at Loma Linda University Cancer Center are committed to providing compassionate, comprehensive, and personalized care throughout your journey. Learn more about cervical cancer screening and treatment options online or call 800-782-2623 .

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  • Patient Care & Health Information
  • Diseases & Conditions
  • Cervical cancer
  • Cervical cancer FAQs

Get answers to the most frequently asked questions about cervical cancer from Mayo Clinic gynecologic oncologist Kristina Butler, M.D., M.S.

Hello. I'm Dr. Kristina Butler, a gynecologic oncologist at Mayo Clinic, and I'm here to answer some of the important questions you might have about cervical cancer.

Pap smear screenings begin at age 21 and continue, varying by age, every three to five years.

Having an abnormal Pap smear is very common, so don't feel alone. It just means that additional tests are needed to prove that cervical cancer isn't present. Most people with abnormal Pap smear do not end up having a diagnosis of cervical cancer.

Most recently, the HPV vaccination has been increased to include all adults male and female to age 45.

Absolutely. After cervical pre-cancer or even HPV exposure, the vaccine remains to provide benefit. We have good evidence to support this. So I recommend HPV vaccination after pre-cancer or even after cervical cancer.

Certainly, we aim to detect cervical cancer as early as possible. Early stage cervical cancer has much improved overall survival and reduced recurrence.

Even though you've been diagnosed with cervical cancer, family planning is still possible. When diagnosed at early stages, we have fertility sparing treatment options that allow a woman to be treated for cervical cancer in some cases and continue to have fertility.

I highly recommend having a medical team that you're comfortable communicating with. It's always safe to ask questions, get second opinions. And remember, at the end of the day, we're all here to help you on the same team. Never hesitate to ask your medical team any questions or concerns you have. Being informed makes all the difference. Thanks for your time and we wish you well.

Pap test

During a Pap test, a tool called a speculum holds the vaginal walls apart. A sample of cells from the cervix is collected using a soft brush and a flat scraping device called a spatula (1 and 2). The cells are placed in a bottle that contains a solution to preserve them (3). Or the cells may be smeared onto a glass slide. Later, the cells are checked under a microscope.

Screening tests can help detect cervical cancer and precancerous cells that may one day develop into cervical cancer. Most medical organizations suggest beginning screening for cervical cancer and precancerous changes at age 21. The tests are usually repeated every few years.

Screening tests include:

Pap test. During a Pap test, a member of your health care team scrapes and brushes cells from your cervix. The cells are then examined in a lab to check for cells that look different.

A Pap test can detect cancer cells in the cervix. It also can detect cells that have changes that increase the risk of cervical cancer. These are sometimes called precancerous cells.

  • HPV DNA test. The HPV DNA test involves testing cells from the cervix for infection with any of the types of HPV that are most likely to lead to cervical cancer.

Discuss your cervical cancer screening options with your health care team.

Cone biopsy

  • Cone biopsy

During a cone biopsy, also called conization, a doctor surgically removes a cone-shaped piece of tissue from the cervix. Typically, the cone-shaped piece includes tissue from both the upper and lower parts of the cervix.

If you might have cervical cancer, testing is likely to start with a thorough exam of your cervix. A special magnifying instrument, called a colposcope, is used to check for signs of cancer.

During the colposcopic exam, a doctor removes a sample of cervical cells for lab testing. To get the sample, you might need:

  • Punch biopsy, which uses a sharp tool to pinch off small samples of cervical tissue.
  • Endocervical curettage, which uses a small, spoon-shaped instrument, called a curet, or a thin brush to scrape a tissue sample from the cervix.

If the results of these tests are concerning, you might have more tests. These might include:

  • Electrical wire loop, which uses a thin, low-voltage electrified wire to take a small tissue sample. Generally, this is done in a doctor's office. You receive medicine to numb the area to lessen any discomfort during the procedure. This test also may be called a loop electrosurgical excision procedure, also known as LEEP.
  • Cone biopsy , also called conization, is a procedure that allows your doctor to take deeper layers of cervical cells for testing. A cone biopsy is often done in a hospital. You may receive medicine to put you in a sleep-like state so that you won't be aware during the procedure.

If you're diagnosed with cervical cancer, you might need other tests to find out the extent of the cancer, also called the stage. Your health care team uses the information from staging tests to plan your treatment.

Tests used for cervical cancer staging include:

  • Imaging tests. Imaging tests make pictures of the body. They can show the location and size of the cancer. Tests might include X-ray, MRI , CT and positron emission tomography (PET) scan.
  • Visual examination of your bladder and rectum. Your doctor may use special scopes to look for signs of cancer inside your bladder and rectum.

The stages of vaginal cancer range from 1 to 4. The lowest number means that the cancer is only in the cervix. As the numbers get higher, the cancer is more advanced. A stage 4 cervical cancer may have grown to involve nearby organs or spread to other areas of the body.

  • Care at Mayo Clinic

Our caring team of Mayo Clinic experts can help you with your cervical cancer-related health concerns Start Here

More Information

Cervical cancer care at Mayo Clinic

  • Cervical dysplasia: Is it cancer?

Treatment for cervical cancer depends on several factors, such as the stage of the cancer, other health conditions you may have and your preferences. Surgery, radiation, chemotherapy or a combination of the three may be used.

Small cervical cancers that haven't grown beyond the cervix are typically treated with surgery. The size of your cancer, its stage and whether you would like to consider becoming pregnant in the future will determine which operation is best for you.

Options might include:

  • Surgery to cut away the cancer only. For a very small cervical cancer, it might be possible to remove all the cancer with a cone biopsy. This procedure involves cutting away a cone-shaped piece of cervical tissue and leaving the rest of the cervix intact. This option may make it possible for you to consider becoming pregnant in the future.
  • Surgery to remove the cervix, called a trachelectomy. A small cervical cancer might be treated with a radical trachelectomy procedure. This procedure removes the cervix and some surrounding tissue. The uterus remains after this procedure, so it may be possible to become pregnant, if you choose.
  • Surgery to remove the cervix and uterus, called a hysterectomy. Most cervical cancers that have not spread beyond the cervix are treated with a radical hysterectomy operation. This involves removing the cervix, uterus, part of the vagina and nearby lymph nodes. A hysterectomy can often cure the cancer and stop it from coming back. But removing the uterus makes it impossible to become pregnant.

Minimally invasive hysterectomy may be an option for very small cervical cancers that have not spread, known as microinvasive cancers. This procedure involves making several small cuts in the abdomen rather than one large cut. People who have minimally invasive surgery tend to recover faster and spend less time in the hospital. But some research has found that minimally invasive hysterectomy may be less effective than traditional hysterectomy. If you're considering minimally invasive surgery, discuss the benefits and risks of this approach with your surgeon.

  • Radiation therapy

Radiation therapy uses powerful energy beams to kill cancer cells. The energy can come from X-rays, protons or other sources. Radiation therapy is often combined with chemotherapy as the primary treatment for cervical cancers that have grown beyond the cervix. It also can be used after surgery if there's an increased risk that the cancer will come back.

Radiation therapy can be given:

  • Externally, called external beam radiation therapy. A radiation beam is directed at the affected area of the body.
  • Internally, called brachytherapy. A device filled with radioactive material is placed inside your vagina, usually for only a few minutes.
  • Both externally and internally.

If you haven't started menopause, radiation therapy might cause menopause. Ask your health care team about ways to preserve your eggs before treatment.

  • Chemotherapy

Chemotherapy uses strong medicines to kill cancer cells. For cervical cancer that has spread beyond the cervix, low doses of chemotherapy are often combined with radiation therapy. This is because chemotherapy may enhance the effects of the radiation. Higher doses of chemotherapy might be recommended to help control symptoms of very advanced cancer. Chemotherapy may be used before surgery to reduce the size of the cancer.

Targeted therapy

Targeted therapy uses medicines that attack specific chemicals in the cancer cells. By blocking these chemicals, targeted treatments can cause cancer cells to die. Targeted therapy is usually combined with chemotherapy. It might be an option for advanced cervical cancer.


Immunotherapy is a treatment with medicine that helps your immune system kill cancer cells. Your immune system fights off diseases by attacking germs and other cells that shouldn't be in your body. Cancer cells survive by hiding from the immune system. Immunotherapy helps the immune system cells find and kill the cancer cells. For cervical cancer, immunotherapy might be considered when the cancer is advanced and other treatments aren't working.

  • Palliative care

Palliative care is a special type of health care that helps you feel better when you have a serious illness. If you have cancer, palliative care can help relieve pain and other symptoms. A team that can include doctors, nurses and other specially trained professionals provides palliative care. The team's goal is to improve quality of life for you and your family.

Palliative care specialists work with you, your family and your care team to help you feel better. They provide an extra layer of support while you have cancer treatment. You can have palliative care at the same time as strong cancer treatments, such as surgery, chemotherapy or radiation therapy.

Using palliative care along with all the other appropriate treatments can help people with cancer feel better and live longer.

  • Brachytherapy

Clinical trials

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

Coping and support

With time, you'll find what helps you cope with the uncertainty and distress of a cancer diagnosis. Until then, you may find that it helps to:

  • Learn enough about cervical cancer to make decisions about your care. Write down your questions for your health care team and ask them at the next appointment. Get a friend or family member to come to appointments with you to take notes. Ask your health care team for further sources of information.
  • Find someone to talk with. You may feel comfortable discussing your feelings with a friend or family member, or you might prefer meeting with a formal support group. Support groups for the families of cancer survivors also are available.
  • Let people help. Cancer treatments can be tiring. Let friends and family know what types of help would be most useful for you.
  • Set reasonable goals. Having goals helps you feel in control and can give you a sense of purpose. But choose goals that you can reach.
  • Take time for yourself. Eating well, relaxing and getting enough rest can help combat the stress and fatigue of cancer.

Preparing for your appointment

Make an appointment with a doctor or other health care professional if you have symptoms that worry you. If a health professional thinks you might have cervical cancer, you may be referred to a doctor who specializes in treating cancers that affect the female reproductive system, called a gynecologic oncologist.

Here's some information to help you get ready for your appointment and what to expect from your health care team.

What you can do

  • Be aware of any pre-appointment restrictions, such as not eating solid food on the day before your appointment.
  • Write down your symptoms, including any that seem to not be related to the reason why you scheduled the appointment.
  • Write down your key medical information, including other conditions.
  • Write down key personal information, including anything that increases your risk of STI s, such as early sexual activity, multiple partners or unprotected sex.
  • Make a list of all your medicines, vitamins or supplements.
  • Ask a relative or friend to come with you, to help you remember what your health care team says.
  • Write down questions to ask your team.

Questions to ask your doctor

  • What's the most likely cause of my symptoms?
  • What kinds of tests do I need?
  • What treatments are available, and what side effects can I expect?
  • What is the prognosis?
  • How often will I need follow-up visits after I finish treatment?

In addition to the questions that you've prepared, don't hesitate to ask other questions that occur to you.

What to expect from your doctor

Be prepared to answer some questions about your symptoms and your health history, such as:

  • What symptoms are you experiencing? How severe are they?
  • When did you first begin experiencing symptoms? Have they changed over time?
  • Have you had regular Pap tests since you became sexually active? Have you ever had irregular Pap test results in the past?
  • Have you ever been treated for a cervical condition?
  • Have you ever been diagnosed with an STI ?
  • Have you ever taken medications that suppress your immune system?
  • Do you or have you ever smoked? How much?
  • Do you want to have children in the future?

Living with cervical cancer?

Connect with others like you for support and answers to your questions in the Gynecologic Cancers support group on Mayo Clinic Connect, a patient community.

Gynecologic Cancers Discussions


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  • Cervical cancer. Cancer.Net. Accessed March 27, 2023.
  • Gershenson DM, et al. Malignant diseases of the cervix. In: Comprehensive Gynecology. 8th ed. Elsevier; 2022. Accessed March 27, 2023.
  • Niederhuber JE, et al., eds. Cancers of the cervix, vulva and vagina. In: Abeloff's Clinical Oncology. 6th ed. Elsevier; 2020. Accessed March 27, 2023.
  • Cervical cancer. National Comprehensive Cancer Network. ps:// Accessed March 27, 2023.
  • AskMayoExpert. Cervical cancer screening (adult). Mayo Clinic; 2022.
  • Palliative care. National Comprehensive Cancer Network. Accessed March 27, 2023.
  • What is cervical cancer? National Cancer Institute. Accessed March 27, 2023.
  • What is cervical cancer? A Mayo Clinic expert explains
  • Where cervical cancer begins

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News from mayo clinic.

  • Mayo Clinic Minute: Cervical cancer screening Jan. 08, 2024, 03:31 p.m. CDT
  • Mayo Clinic Health System now offering Saturday appointments for cervical cancer screening June 14, 2023, 05:15 p.m. CDT
  • Mayo Clinic Minute: Screening for cervical cancer Jan. 12, 2023, 05:30 p.m. CDT
  • Mayo Clinic Q and A: Cervical cancer and HPV screening Jan. 11, 2023, 04:00 p.m. CDT
  • 4 ways to reduce risks of cervical cancer Jan. 10, 2023, 03:00 p.m. CDT
  • Mayo Clinic Minute: Why Black women need to be screened for cervical cancer Sept. 05, 2022, 02:00 p.m. CDT

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What affects your chances of surviving cervical cancer?

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Despite the strong preventative measures in place, 3,200 cases of cervical cancer are diagnosed every year in the UK. And according to Cancer Research UK, more than 50% of those diagnosed survive for 10 years or more.

Here we look at what can affect cervical cancer survival rates.

What's the survival rate of cervical cancer?

The survival rate for cervical cancer depends on many different factors, such as your age and health, but one of the most important factors is how early it is diagnosed. In its early stages, or at the first signs of cell changes that might lead to cancer, cervical cancer can be effectively treated. However, late diagnosis can make an enormous difference.

"Early diagnosis is incredibly important with cervical cancer," says molecular engineer and cancer researcher, Dr Angela Pine. Of those diagnosed with stage 1 cervical cancer, more than 90% will survive for more than a year. But with a diagnosis of stage 4, that number drops to 50%."

We explore what can affect your chances of survival from cervical cancer.

Cervical cancer signs and what to look for

Cervical cancer is one of the most common cancers in women in the UK, with more than 3,000 cases...

Cervical cancer signs and what to look for

What to expect when you have a colposcopy

What are the common myths and facts about cervical screening?

What are the common myths and facts about cervical screening?

Improvements in treatment.

Research into preventing and treating all types of cancer is ongoing, with new treatments on the horizon. And, like many other forms of cancer, the survival rate for cervical cancer has improved over the past decade.

"We have seen survival rates in the UK improve and they have been doing so for quite some time," says Pine. She adds that this may have changed during the pandemic years due to reduced access for cervical screening appointments, but data has yet to be released.

There is no doubt the progress made should be celebrated. However, the screening and preventative measures available for cervical cancer could almost eliminate the disease entirely 1 , so there is still much to be done.

Attending your cervical screening

Cervical screening is effective at identifying or ruling out the woman at risk of cervical cancer. However, only 40-50% of women and people with cervices who are invited for a screening test take up the offer.

The screening tests both for high-risk HPV (Human Papillion Virus - a virus transmitted by close bodily contact and responsible for 99.8% of cervical cancer cases) - and for pre-cancerous cells. Therefore, attending the test could mean that your cancer can be treated and eliminated before it takes a meaningful hold.

Low uptake of screening tests, however, means that in many cases, cervical cancer is being diagnosed at a later stage than it should be.

Also, a vaccine programme against HPV has been in place since 2009 for girls - and 2016 for boys - that aims to protect people from contracting the virus in the first place. While uptake of the vaccine is fairly high - around 70% - this rate could still be improved.

There are a number of reasons why women may be hesitant to attend their cervical screening (smear test).

Discomfort and embarrassment

The screening involves a sample of cells being taken from the cervix. Although pain is minimal, the procedure can be uncomfortable and feel scary . And because it is a gynaecological examination, some women may find it embarrassing.

Fear or trauma

Some women feel reluctant to attend the test because of its invasive nature. The idea of a gynaecological examination can be daunting for some, and may even be traumatic - especially to survivors of sexual abuse .

Lack of understanding

While charities and health care providers are working hard to get the message out there, not everyone fully understands the importance of cervical cancer screening, or realises the important part it plays in cancer prevention. There are also several myths that can put women off attending.

Spotting the symptoms

If you miss your cervical screening or are overdue your screening - book in with your GP practice to get your cervical screening as soon as you can, otherwise, the only other way to spot cervical cancer is once you have symptoms. In its early stages, cervical cancer is usually symptom free. This means that if you rely on symptom spotting alone, you could be diagnosed late when the cancer has already progressed.

It's also possible that if you do have symptoms, it can take a while for them to be linked with cervical cancer. This is because they can also be a sign of other health problems that a doctor has to investigate and rule out.

Common symptoms of cervical cancer include

  • Bleeding after sex.
  • Pain or discomfort during sex.
  • Unusual vaginal bleeding - bleeding in between periods or periods are longer or heavier.
  • Changes to vaginal discharge.
  • Bleeding after menopause.
  • Pain in your lower back, pelvis and stomach that doesn't go away

All of these symptoms could be signs of something other than cervical cancer, but don't dismiss or ignore them. It's important to seek medical advice if you experience the above symptoms and, if necessary, to raise the possibility of cervical cancer with your doctor.

"It's about knowing your body and what's normal for you" explains Kate Sanger, spokesperson for cervical cancer charity Jo's Trust. "Make sure you outline the symptoms carefully to your GP. There is guidance available for clinicians, and if you present with these symptoms they need to explore further into all possible causes."

Further reading

  • Cancer Research UK: Cervical cancer statistics
  • Pain in your lower back, pelvis and lower stomach.

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Related Information

  • Why you shouldn't skip your smear test
  • Ovarian Cancer
  • Vulval Cancer
  • Cervical Cancer
  • The female reproductive system (anatomy, the menstrual cycle, and ovulation)

Cervical cancer signs and what to look for

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Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Egton Medical Information Systems Limited has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions .

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024


  • 1 Memorial Sloan Kettering Cancer Center.
  • 2 UC San Diego Moores Cancer Center.
  • 3 O'Neal Comprehensive Cancer Center at UAB.
  • 4 Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
  • 5 University of Wisconsin Carbone Cancer Center.
  • 6 UC Davis Comprehensive Cancer Center.
  • 7 Dana-Farber/Brigham and Women's Cancer Center.
  • 8 Duke Cancer Institute.
  • 9 Moffitt Cancer Center.
  • 10 Vanderbilt-Ingram Cancer Center.
  • 11 Yale Cancer Center/Smilow Cancer Hospital.
  • 12 University of Colorado Cancer Center.
  • 13 Roswell Park Comprehensive Cancer Center.
  • 14 Huntsman Cancer Institute at the University of Utah.
  • 15 Abramson Cancer Center at the University of Pennsylvania.
  • 16 City of Hope National Medical Center.
  • 17 Indiana University Melvin and Bren Simon Comprehensive Cancer Center.
  • 18 Stanford Cancer Institute.
  • 19 UT Southwestern Simmons Comprehensive Cancer Center.
  • 20 Fox Chase Cancer Center.
  • 21 Mayo Clinic Comprehensive Cancer Center.
  • 22 Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.
  • 23 The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute.
  • 24 Fred & Pamela Buffett Cancer Center.
  • 25 UCLA Jonsson Comprehensive Cancer Center.
  • 26 St. Jude Children's Research Hospital/The University of Tennessee Health Science Center.
  • 27 University of Michigan Rogel Cancer Center.
  • 28 Mass General Cancer Center.
  • 29 The University of Texas MD Anderson Cancer Center.
  • 30 UCSF Helen Diller Family Comprehensive Cancer Center.
  • 31 Fred Hutchinson Cancer Center.
  • 32 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
  • 33 Patient Advocate.
  • 34 National Comprehensive Cancer Network.
  • PMID: 38081139
  • DOI: 10.6004/jnccn.2023.0062

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / pathology
  • Uterine Cervical Neoplasms* / therapy

Cervical Cancer Treatment

Different types of treatment are available for cervical cancer . You and your cancer care team will work together to decide your treatment plan, which may include more than one type of treatment. Many factors will be considered, such as the stage of the cancer, your overall health, and your preferences. Your treatment plan will include information about your cancer, the goals of treatment, the treatment options and possible side effects, and the expected length of treatment.

If you are concerned about whether treatment will affect your fertility , talk with your cancer care team before treatment begins about what to expect. To learn about fertility preservation options and ways to find support, see Fertility Issues in Girls and Women with Cancer .

For treatments by stage of cervical cancer, see Cervical Cancer Treatment by Stage .

For information about treatment during pregnancy, see Cervical Cancer Treatment during Pregnancy .

Surgery (also called an operation) is sometimes used to treat cervical cancer. The type of surgery depends on where the cancer is located. Learn more about Surgery to Treat Cancer .

The following surgical procedures may be used:

Cold knife conization

Cold knife conization uses a scalpel to remove a cone-shaped piece of tissue from the cervix and cervical canal. Sometimes all the cancer can be removed during this procedure. Cold knife conization is done in the hospital under general anesthesia .

Conization may also be used to treat high-grade cervical cell changes .

Sentinel lymph node biopsy

Sentinel lymph node biopsy removes the sentinel lymph node during surgery. The sentinel lymph node is the first lymph node in a group of lymph nodes to receive lymphatic drainage from the primary tumor . It is therefore the first lymph node the cancer is likely to spread to from the primary tumor. To identify the sentinel lymph node, a radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are found, more lymph nodes will be removed through a separate incision (cut). This is called a lymph node dissection. After the sentinel lymph node biopsy, the surgeon removes the cancer.

Learn more about Sentinel Lymph Node Biopsy .


A hysterectomy is surgery to remove the uterus . As a treatment for cervical cancer, the cervix, and sometimes the surrounding structures, are removed. Several types of hysterectomy may be used to treat cervical cancer:

Hysterectomy; drawing shows the female reproductive anatomy, including the ovaries, uterus, vagina, fallopian tubes, and cervix. Dotted lines show which organs and tissues are removed in a total hysterectomy, a total hysterectomy with salpingo-oophorectomy, and a radical hysterectomy. An inset shows the location of two possible incisions on the abdomen: a low transverse incision is just above the pubic area and a vertical incision is between the navel and the pubic area.

  • Radical hysterectomy removes the uterus, cervix, part of the vagina, and a wide area of ligaments and tissues around these organs. The ovaries , fallopian tubes , or nearby lymph nodes may also be removed.
  • Modified radical hysterectomy removes the uterus, cervix, upper part of the vagina, and ligaments and tissues that closely surround these organs. This type of surgery removes fewer tissues and/or organs than radical hysterectomy. The ovaries, fallopian tubes, or nearby lymph nodes may also be removed.

Radical trachelectomy

Radical trachelectomy (also called radical cervicectomy) removes the cervix, nearby tissue, and the upper part of the vagina. Lymph nodes may also be removed. After the surgeon removes the cervix, they attach the uterus to the remaining part of the vagina. A special stitch or band is placed on the uterus (in a procedure called a cerclage) to help keep the uterus closed during pregnancy. If you have this surgery, you may still be able to become pregnant.

Bilateral salpingo-oophorectomy

Bilateral salpingo-oophorectomy removes both ovaries and both fallopian tubes. This is done when the cancer has spread to these organs.

Total pelvic exenteration

Total pelvic exenteration removes the lower colon , rectum , and bladder . The cervix, vagina, ovaries, and nearby lymph nodes are also removed. Artificial openings (stoma) are made for urine and stool to flow from the body to a collection bag. Plastic surgery may be needed to make an artificial vagina after this operation.

Radiation therapy

Radiation therapy uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing by damaging their DNA . The two main types of radiation therapy are external radiation therapy and internal radiation therapy (also called brachytherapy).

Both external and internal radiation therapy are used to treat cervical cancer and may also be used as palliative therapy to relieve symptoms and improve quality of life in people with advanced cervical cancer.

External radiation therapy

External-beam radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer. Intensity-modulated radiation therapy (IMRT) is a way of giving external radiation therapy that can help keep radiation from damaging nearby healthy tissue.

IMRT is a type of 3-dimensional (3-D) radiation therapy that uses a computer to make pictures of the size and shape of the tumor. Thin beams of radiation of different intensities (strengths) are aimed directly at the tumor from many angles. IMRT is being studied for the treatment of cervical cancer.

Learn more about External Beam Radiation Therapy for Cancer .

Internal radiation therapy

Internal radiation therapy uses a radioactive substance sealed in needles, seeds , wires, or catheters that are placed directly into or near the cancer. Internal radiation therapy is also called brachytherapy.

Learn more about Brachytherapy to Treat Cancer .


Chemotherapy (also called chemo) uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given alone or with other types of treatment.

Chemotherapy drugs used to treat cervical cancer include

  • carboplatin
  • gemcitabine
  • vinorelbine

Combinations of these drugs may be used. Other chemotherapy drugs not listed here may also be used.

Learn more about how chemotherapy works against cancer, how it is given, common side effects, and more in Chemotherapy to Treat Cancer .

Targeted therapy

Targeted therapy uses drugs or other substances to block the action of specific enzymes , proteins, or other molecules involved in the growth and spread of cancer cells.

Targeted therapies used to treat cervical cancer include

  • bevacizumab
  • tisotumab vedotin

Learn more about how targeted therapy works against cancer, how it is given, possible side effects, and more in Targeted Therapy to Treat Cancer .


Immunotherapy helps a person's immune system fight cancer. Biomarker tests can be used to help predict your response to certain immunotherapy drugs. Learn more about Biomarker Testing for Cancer Treatment .

Pembrolizumab is an immunotherapy drug used to treat certain patients whose cervical cancer has the biomarker PD-L1 .

Learn more about how immunotherapy works against cancer, how it is given, possible side effects, and more in Immunotherapy to Treat Cancer .

Clinical trials

A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. For some patients, taking part in a clinical trial may be an option.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. Clinical trials supported by other organizations can be found on the website.

To learn more about clinical trials, see Clinical Trials Information for Patients and Caregivers . You can also contact NCI's Cancer Information Service via chat, email, or phone (both in English and Spanish) for help finding a clinical trial.

Follow-up care during and after treatment

As you go through treatment, you will have follow-up tests or checkups. Some of the tests that were done to diagnose cervical cancer or to find out the stage of the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back).

Tell your doctor if you have any of the following signs or symptoms, which may mean the cancer has come back:

  • vaginal bleeding or discharge
  • pain in the abdomen, back, or leg
  • swelling in the leg
  • trouble urinating
  • change in your bowel movements
  • feeling tired

For cervical cancer, follow-up tests are usually done every 3 to 4 months for the first 2 years, followed by checkups every 6 months. The checkup includes a current health history and exam of the body to check for signs and symptoms of recurrent cervical cancer and for late effects of treatment. A Pap test may or may not be done during your visits.

Learn more about what to expect when treatment ends .

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  • Open access
  • Published: 04 December 2019

“Patient Journeys”: improving care by patient involvement

  • Matt Bolz-Johnson 1 ,
  • Jelena Meek 2 &
  • Nicoline Hoogerbrugge 2  

European Journal of Human Genetics volume  28 ,  pages 141–143 ( 2020 ) Cite this article

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  • Cancer genetics
  • Cancer screening
  • Cancer therapy
  • Health policy

“I will not be ashamed to say ‘ I don’t know’ , nor will I fail to call in my colleagues…”. For centuries this quotation from the Hippocratic oath, has been taken by medical doctors. But what if there are no other healthcare professionals to call in, and the person with the most experience of the disease is sitting right in front of you: ‘ your patient ’.

This scenario is uncomfortably common for patients living with a rare disease when seeking out health care. They are fraught by many hurdles along their health care pathway. From diagnosis to treatment and follow-up, their healthcare pathway is defined by a fog of uncertainties, lack of effective treatments and a multitude of dead-ends. This is the prevailing situation for many because for rare diseases expertise is limited and knowledge is scarce. Currently different initiatives to involve patients in developing clinical guidelines have been taken [ 1 ], however there is no common method that successfully integrates their experience and needs of living with a rare disease into development of healthcare services.

Even though listening to the expertise of a single patient is valuable and important, this will not resolve the uncertainties most rare disease patients are currently facing. To improve care for rare diseases we must draw on all the available knowledge, both from professional experts and patients, in order to improve care for every single patient in the world.

Patient experience and satisfaction have been demonstrated to be the single most important aspect in assessing the quality of healthcare [ 2 ], and has even been shown to be a predictor of survival rates [ 3 ]. Studies have evidenced that patient involvement in the design, evaluation and designation of healthcare services, improves the relevance and quality of the services, as well as improves their ability to meet patient needs [ 4 , 5 , 6 ]. Essentially, to be able to involve patients, the hurdles in communication and initial preconceptions between medical doctors and their patients need to be resolved [ 7 ].

To tackle the current hurdles in complex or rare diseases, European Reference Networks (ERN) have been implemented since March 2017. The goal of these networks is to connect experts across Europe, harnessing their collective experience and expertise, facilitating the knowledge to travel instead of the patient. ERN GENTURIS is the Network leading on genetic tumour risk syndromes (genturis), which are inherited disorders which strongly predispose to the development of tumours [ 8 ]. They share similar challenges: delay in diagnosis, lack of cancer prevention for patients and healthy relatives, and therapeutic. To overcome the hurdles every patient faces, ERN GENTURIS ( ) has developed an innovative visual approach for patient input into the Network, to share their expertise and experience: “Patient Journeys” (Fig.  1 ).

figure 1

Example of a Patient Journey: PTEN Hamartoma Tumour Syndrome (also called Cowden Syndrome), including legend page ( )

The “Patient Journey” seeks to identify the needs that are common for all ‘ genturis syndromes ’, and those that are specific to individual syndromes. To achieve this, patient representatives completed a mapping exercise of the needs of each rare inherited syndrome they represent, across the different stages of the Patient Journey. The “Patient Journey” connects professional expert guidelines—with foreseen medical interventions, screening, treatment—with patient needs –both medical and psychological. Each “Patient Journey” is divided in several stages that are considered inherent to the specific disease. Each stage in the journey is referenced under three levels: clinical presentation, challenges and needs identified by patients, and their goal to improve care. The final Patient Journey is reviewed by both patients and professional experts. By visualizing this in a comprehensive manner, patients and their caregivers are able to discuss the individual needs of the patient, while keeping in mind the expertise of both professional and patient leads. Together they seek to achieve the same goal: improving care for every patient with a genetic tumour risk syndrome.

The Patient Journeys encourage experts to look into national guidelines. In addition, they identify a great need for evidence-based European guidelines, facilitating equal care to all rare patients. ERN GENTURIS has already developed Patient Journeys for the following rare diseases ( ):

PTEN hamartoma tumour syndrome (PHTS) (Fig.  1 )

Hereditary breast and ovarian cancer (HBOC)

Lynch syndrome

Neurofibromatosis Type 1

Neurofibromatosis Type 2


A “Patient Journey” is a personal testimony that reflects the needs of patients in two key reference documents—an accessible visual overview, supported by a detailed information matrix. The journey shows in a comprehensive way the goals that are recognized by both patients and clinical experts. Therefore, it can be used by both these parties to explain the clinical pathway: professional experts can explain to newly identified patients how the clinical pathway generally looks like, whereas their patients can identify their specific needs within these pathways. Moreover, the Patient Journeys could serve as a guide for patients who may want to write, in collaboration with local clinicians, diaries of their journeys. Subsequently, these clinical diaries can be discussed with the clinician and patient representatives. Professionals coming across medical obstacles during the patient journey can contact professional experts in the ERN GENTURIS, while patients can contact the expert patient representatives from this ERN ( ). Finally, the “Patient Journeys” will be valuable in sharing knowledge with the clinical community as a whole.

Our aim is that medical doctors confronted with rare diseases, by using Patient Journeys, can also rely on the knowledge of the much broader community of expert professionals and expert patients.

Armstrong MJ, Mullins CD, Gronseth GS, Gagliardi AR. Recommendations for patient engagement in guideline development panels: a qualitative focus group study of guideline-naive patients. PloS ONE 2017;12:e0174329.

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This work is generated within the European Reference Network on Genetic Tumour Risk Syndromes – FPA No. 739547. The authors thank all ERN GENTURIS Members and patient representatives for their work on the Patient Journeys (see ).

Author information

Authors and affiliations.

SquareRootThinking and EURORDIS – Rare Diseases Europe, Paris, France

Matt Bolz-Johnson

Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands

Jelena Meek & Nicoline Hoogerbrugge

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Bolz-Johnson, M., Meek, J. & Hoogerbrugge, N. “Patient Journeys”: improving care by patient involvement. Eur J Hum Genet 28 , 141–143 (2020).

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patient journey cervical cancer

The Healthy

Here’s What to Know About Cervical Cancer Symptoms, Screenings, and Treatment, Say Expert Doctors

I f you were asked to name the top cancers that affect women, breast cancer is sure to be among the first, perhaps with colon cancer or skin cancer near the top of your list. Cervical cancer isn’t high on the mainstream radar, but it’s one of the top five most common cancers that affect women or people with vaginas.

According to the American Cancer Society, about 14,000 new cases of cervical cancer are diagnosed and 4,000 to 5,000 women die each year in the United States. But that’s not the only important statistic: An additional 200,000 women are diagnosed with cervical pre cancers each year.

These numbers are likely a significant underestimation, as only two-thirds of women are getting regularly tested for it, says Pari Ghodsi, MD, an OB/GYN and women’s health specialist in Los Angeles, CA.

“The sad fact about cervical cancer is that the majority of these deaths were preventable through the HPV vaccine and proper screening and treatment,” she says. “Saving womens’ lives starts with greater awareness of cervical cancer and increased access to the vaccine and regular screenings. When it’s caught early, it’s one of the most treatable cancers.”

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What is cervical cancer?

“Cervical cancer is a growth of cancerous cells that starts in the cervix,” says Kim L. Thornton, MD , a board-certified reproductive endocrinologist at Boston IVF and assistant professor at Harvard Medical School.

So, what is the cervix? Despite the fact that every female assigned at birth has a cervix, many people have never heard of cervical cancerand that may be because folks (even those with cervixes) don’t know what or where the cervix is.Dr. Thornton explains that the cervix is a doughnut-shaped organ that makes up the lower one-third of the uterus, considered to be the “neck” of the uterus that separates the uterus from the vaginal canal. The cervix measures three to five centimeters in length and two to three centimeters in diameter.

The cervix responds to hormone changes, making it quite a dynamic organ. Dr. Thornton explains that throughout a woman’s life, the cervix can soften, flex, lengthen, thin, dilate, and other functions required for menstruation, conception, pregnancy and childbirth.“Sperm travels through it, menstrual fluid passes out of it, and, of course, babies exit through it. It also acts as a barrier for infection,” Dr. Thornton says.

The cervix is made up of two parts. The exocervix is the bottom of the cervix, or the part the doctor can see when performing an internal pelvic exam (yes, the “scoot down further!” type with the speculum). The endocervix is the top part that goes into the uterus. Both parts of the cervix are made up of a different type of cell, and where they meet in the middle is called the “transformation zone.” Most cervical cancers begin in the cells in the transformation zone.

Do Pap Smears Hurt? How to Make Pap Smears More Comfortable

Types of cervical cancer

There are two main types of cervical cancer:

Squamous cell carcinoma

Over 90% of all cervical cancers are this type, according to the American Cancer Society. These cancers develop from squamous cells in the exocervix, most often starting in the transformation zone.


The other 10% of cervical cancers are adenocarcinomas, or cancers that develop from glandular cells found in the endocervix.

Rarely, there are cervical cancers that have features of both squamous cell carcinomas and adenocarcinomas. These are called mixed or adenosquamous carcinomas.

Heres How I Knew I Had Cervical Cancer: One Survivors Story of Discovering Unexpected Symptoms

Causes of cervical cancer

Over 90% of cases of cervical cancer are caused by human papillomaviruses (HPV), a class of viruses transmitted through sexual contact. HPV “turns off” tumor-suppressing genes in the cell. This can cause the cells of the cervix to grow too much and cause a cascade of additional genetic changes. In some cases this can lead to cancer. It should be noted that most people who have HPV will not develop cervical cancer.

10 Myths About HPV That Could Damage Your Health

For people who get cervical cancer and don’t test positive for HPV, it may be caused by anything that damages the body’s cells, like smoking, or compromises the immune system, like an HIV infection.

Risk factors for cervical cancer

The biggest risk factor for cervical cancer is having a cervixbeing a female assigned at birth.

“One of the more scary myths I see about cervical cancer is that gay women or transgender men have less risk of cervical cancer or cannot get it,” Dr. Ghodsi says. “This is not true and they should get screened on the same schedule as heterosexual and cis women.”

Next is your age. This type of cancer is most frequently diagnosed in women aged 35 to 44, with the average age at diagnosis being 50 years old, according to the American Cancer Society. It is rare to find it in women under 20, but more than 20% of cases of cervical cancer are found in women over age 65. However, these cases in older women rarely occur if the woman has been getting regular tests to screen for cervical cancer before they were 65yet another plug for regular screenings!

Then take a look at your sexual history. Because HPV is the most common cause of cervical cancer and it is a sexually transmitted infection, the earlier a woman becomes sexually active, the longer a woman is sexually active and the more partners she has, the higher her risk of getting HPV.

Other known risk factors of cervical cancer include:

HIV or a compromised immune system

A previous chlamydia infection

Being on the birth control pill for years

Having multiple full-term pregnancies

Having a first baby at younger than 20 years old

Poor nutrition

A family history of cervical cancer

7 Early Signs of Cervical Cancer, According to an OBGYN

Symptoms of cervical cancer

Cervical cancer is often missed in the early stages because cervical cancer symptoms can be subtle and easily mistaken for other things, Dr. Thornton says.In fact, it’s quite common for women to not notice any symptoms at all at the beginning or have “silent symptoms.”

“Here’s How I Knew I Had Cervical Cancer”: One Survivor’s Story of Discovering Unexpected Symptoms

The symptoms often don’t appear until the cancer becomes larger, growing into nearby tissue. At this stage, the most common symptoms include:

Bleeding after vaginal sex

Vaginal bleeding after menopause

Irregular periods

Longer, heavier periods

Unusual discharge from the vagina, either clear or tinged with blood

Pain during sex

Pain or pressure in the pelvic region

As the disease advances, other symptoms may include:

Swollen legs

Problems urinating or having a bowel movement

Bloody urine

11 Sneaky Reasons Behind a Missed Period (Besides Pregnancy)

Testing for cervical cancer

“With regular testing we can catch it early, while it’s still curable, or even prevent precancerous cells from developing into cancer,” Dr. Ghodsi says. “No woman should die from cervical cancer and we must push for more women to be screened.”

The goal of cervical cancer screening is to find abnormal cells in the cervix or cervical cancer early when it is more treatable and curable. The primary tools for screening for cervical cancer are regular HPV tests and pap smears .

During a pelvic exam, the doctor will lightly scrape the surface of your cervix and send those cells to a lab where they will be tested for the high-risk types of HPV that are more likely to cause cancer. Just because you test positive for HPV does not mean it will develop into cancer. HPV infection has no treatment, but the vaccine can help prevent getting it.

I Have High-Risk HPV. Now What? Doctors Share Advice (and Assurance)

Similarly, the cervical cells gathered during the pelvic exam can be examined under a microscope to look for precancerous changes.

After an Abnormal Pap: 4 Things You Should Do Next

The American Cancer Society recommends that all individuals with a cervix follow these cancer-screening guidelines:

  • Age 25: Get your first cervical cancer screening
  • Age 25 to 65: Get a primary HPV test every five years. This may be combined with a Pap smear. Otherwise, if you’re getting just a Pap smear, get one at least every three years. (Many doctors advise that an annual Pap test is preferable.)
  • Age 66 and older: If you’ve had a regular screening in the past 10 years with normal results, then you may no longer need screening for cervical cancer.
  • The American Cancer Society adds: “If you have a history of a serious pre-cancer, you should continue to have testing for at least 25 years after that condition was found, even if the testing goes past age 65.”

An abnormal pap smear combined with a positive HPV test will alert your doctor to investigate further.

How Often Should You Get a Pap Smear?

How cervical cancer is diagnosed

Cervical cells don’t suddenly go from healthy to cancerrather, it’s a process, Dr. Thornton explains. It starts when normal cells gradually develop abnormal changes that over time can turn into cancer. If your cells are abnormal but not yet cancerous, you’ll likely be diagnosed with “precancer.”

These precancerous cells are graded on a scale of 1 to 3 based on how much of the cervical tissue looks abnormal.

In stage 1 (or CIN1), most of the tissue looks normal and often the abnormal cells will change back to normal over time.

In stages 2 and 3 (CIN2 or CIN3), more of the cells look abnormal. This indicates a higher risk that the cells can become cancer and will need to be monitored closely or removed.

All cervical cancers start with abnormal cells, but not every person with abnormal cervical cells will get cervical cancer. In fact, for most women, these abnormal cells will go away without any treatment. But because sometimes they do turn into invasive cancer, screening and follow-up care for all abnormal cells is necessary, Dr. Ghodsi says.

“When caught early, we can prevent precancerous cells from developing into cancer,” Dr. Ghodsi says.

The FDA Just Released a New Requirement for Mammograms

Treating cervical cancer

Treatments for cervical cancer include surgery, radiation therapy, chemotherapy, targeted drug therapy, and immunotherapy. Which treatments you need will depend on the type of cancer you are diagnosed with and the stage of its progression.

Early stages of cervical cancer are often treated with either surgery or radiation combined with chemotherapy. Later stages are treated with radiation combined with chemotherapy. Chemotherapy on its own is often used to treat advanced cervical cancer. A gynecological oncologist is a doctor who specializes in helping patients find the right treatment plan for cervical cancer.

Preventing cervical cancer

“The best way to prevent cervical cancer is to get the HPV vaccine , and both men and women should get it,” Dr. Ghodsi says.

The first HPV vaccine is recommended for young people around age 12, before sexual activity is started. It is recommended the series of two shots be completed by age 26 for young women and age 21 for young men. After these ages, the vaccine provides little or no protection so it’s not generally recommended.

The vaccine should always be used in combination with regular HPV tests and pap smearshaving the vaccine doesn’t remove the need for regular screening, she adds.

Always practice safe sex to reduce your risk of contracting HPV, including using condoms and getting regular STD screenings.

Because there is a connection between stress and HPV infections , doctors also recommend lowering your stress as a way to help prevent cervical cancer.

In addition to reducing your exposure to HPV, recent research has found that women who have ever used an intrauterine device (IUD) had a lower risk of cervical cancer throughout their lifetime, even after the IUD was removed.

And if you are a smoker, the best time to quit smoking is now.

12 Things That Happen to Your Body When You Stop Vaping

Additional resources

Facts About Cervical Cancer

CDC: Cervical Cancer

American Cancer Society: Cervical Cancer

For more wellness updates, subscribe to The Healthy @ Reader’s Digest newsletter and follow The Healthy on Facebook and Instagram . Keep reading:

  • New Study: White Bread and Alcohol Linked to Colorectal Cancer

Here’s How Often You Can Take Ibuprofen, Say Expert Doctors

New Study: Reducing This Ingredient Works as Well as Blood Pressure Medication

I Ate Potatoes Every Day for a WeekHere’s What Happened

The post Here’s What to Know About Cervical Cancer Symptoms, Screenings, and Treatment, Say Expert Doctors appeared first on The Healthy .

Doctor doing Smear Test for Cervical Cancer Symptoms


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Cervical Cancer: The Patient Journey

Linda Ryan, a patient advocate, details her treatment journey with cervical cancer and discusses resources available to patients.

patient journey cervical cancer

EP: 1 . Overview of Cervical Cancer

patient journey cervical cancer

EP: 2 . Cervical Cancer: The Patient Journey

Ep: 3 . patient perceptions of cervical cancer screening, ep: 4 . treatment options for patients with primary or recurrent cervical cancer, ep: 5 . treatments for patients with newly diagnosed metastatic cervical cancer, ep: 6 . individualized treatment selection in cervical cancer, ep: 7 . tisotumab vedotin for patients with cervical cancer, ep: 8 . unmet needs in the cervical cancer treatment landscape, ep: 9 . shared decision-making in cervical cancer, ep: 10 . cervical cancer: advocating for yourself and communicating with family, ep: 11 . cervical cancer: insight into the patient experience, ep: 12 . myths around cervical cancer.

A panel of 3 experts on cervical cancer seated on chairs in a studio

Keytruda Plus CRT Offers ‘Better Chance of Cure’ in Advanced Cervical Cancer

The Food and Drug Administration (FDA) has recently approved Keytruda (pembrolizumab) plus chemoradiotherapy for the treatment of patients with stages 3 to 4A cervical cancer.

A Chance of Cure for Cervical Cancer, Lymphedema Treatment Act and More

A Chance of Cure for Cervical Cancer, Lymphedema Treatment Act and More

We take a look at the first FDA approval in the oncology space for 2024, the Lymphedema Treatment Act and more.

Tiydak Improves Survival in Cervical Cancer

Tivdak Confers 30% Reduction in Mortality Risk in Cervical Cancer

A 30% reduction in the risk of death versus. investigator’s choice of chemotherapy as second or third line therapy was concluded when Tivdak was combined for the treatment of recurrent or metastatic cervical cancer with disease progression on doublet chemotherapy.

Kate Weissman, a gynecologic cancer survivor

Fertility Research ‘Long Overdue’ for Patients With Cervical Cancer

Cervical cancer survivor Kate Weissman talks recent research on follow-up visits for patients after fertility-sparing surgery, and explains why it’s ‘something that the cervical cancer community is owed.’

Long term side effects of cervical cancer maybe be reduced by sexual activity

Sexual Activity May Reduce Long-Term Side Effects After Cervical Cancer

Survivors of cervical cancer who engage in sexual activity or vaginal dilation after radiation could be at lower risk for developing long term side effects.

Tivdak Improves Survival Rates in Advanced Cervical Cancer

Tivdak Improves Survival Rates in Advanced Cervical Cancer

Tivdak improved overall survival in patients with recurrent or metastatic cervical cancer, compared with chemotherapy alone.

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Strength in Every Step: Linda Ryan’s Journey Through Cervical Cancer and Exercise

patient journey cervical cancer

Linda Ryan, Patient Advocate

In the face of a life-changing cancer diagnosis, patient advocate Linda Ryan discovered an unexpected ally in her battle against cervical cancer: exercise. Linda, who had never been an athlete or engaged in organized sports, found solace, strength, and a renewed sense of control through physical activity.  

Linda’s exercise journey began with walking, a simple yet powerful activity that became her primary form of exercise after having children. From walking, she transitioned to running, emphasizing that her pace may have been slower than others walked, but it was a personal achievement, nonetheless. At 43 years old, Linda accomplished a marathon, a feat that marked a turning point in her life.  

In a turn of events, Linda discovered an enlarged lymph node in her neck just four weeks after the marathon, signaling the first recurrence of early-stage cervical cancer diagnosed seven years prior. Undeterred, Linda sought guidance from her gynecologic oncologist who encouraged her to keep moving as much as possible.  

“Running not only gave my body strength, but it gave me incredible mental strength,” Linda emphasized. Facing a bone scan before treatment, she went on a short and slow run, believing that every step made her bones stronger and sent a clear message to the cancer that it wasn’t welcome.  

As her cancer journey progressed through six recurrences, involving surgeries, chemotherapy, and radiation treatments, exercise became a lifeline for Linda. Even during moments of extreme fatigue, she recognized the mental benefits of movement. Linda recalled, “Exercise became nearly non-existent, but I knew I needed to move to feel better mentally.”  

As a patient advocate, Linda encourages other patients to embrace any form of movement, even if it’s just a short walk to the mailbox. “While it may not be significant in distance, it still can give a sense of accomplishment, power, and control – all things that we often lose as cancer patients,” she added.  

Despite the challenges, Linda resumed exercising after surgeries and during chemotherapy. Opting for Pilates, a gentler alternative, she found motivation and consistency in her routine. “Exercise has given me the edge over cancer that I’ve used to get through the difficult times,” Linda explained.  

Now attending Pilates three to four days a week, Linda has made exercise a crucial part of her post-treatment life, emphasizing its role in maintaining strength, mobility, and mental well-being. Her story stands as a testament to the transformative power of exercise, inspiring others to find strength in every step of their own cancer journeys.  

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6 articles to clue you up on HPV, vaccines, and cervical cancer prevention

Jacob Smith

22 January 2024

Stained cervical cells viewed under the microscope

Virtually all cases of cervical cancer cases are preventable.  

In 2020, the World Health Organisation announced an ambitious plan to create a ‘cervical cancer-free future’. If we succeed, cervical cancer will become the first cancer to be ‘eliminated’ on this scale so almost no one gets it.  

This week (22-28 January) is Cervical Cancer Prevention Week, and to recognise that, we’re focussing on how, with research and a combination of vaccination and screening, we can make cervical cancer a thing of the past.  

We’ve rounded up some of our most useful content on cervical cancer, from research in the lab to screening in the clinic, to get you up to date on how we can prevent cervical cancer.  

1. Common questions about HPV answered  

Virtually all cases of cervical cancer are caused by the human papillomavirus (HPV), a link we helped to prove in the 1990s.  

That might sound worrying, but it’s important to remember that although HPV can cause some types of cancer, having HPV doesn’t mean you have or will definitely get cancer.  

Electron microscopy image of HPV

In fact, most of us will have HPV at some point in our lifetime without it causing any harm and a lot of the time without us knowing.  

While HPV might not be the most comfortable topic of conversation, we know that you may have questions about it.   

So, we’ve answered some of the most common questions our nurses have been asked about HPV.  

  • Let’s talk HPV – Read the answers to 6 common questions  

2. Understanding HPV in screening  

Cervical screening is one of 3 cancer screening programmes in the UK. It is offered to most women, some trans men and non-binary people with a cervix, aged 25 to 64.  

Screening involves testing apparently healthy people without symptoms. It can save lives by finding cancers at an early stage, or even in the case of cervical cancer, preventing them.  

In the UK, cervical screening is done using HPV primary testing, which tests the sample of cervical cells for HPV first. The laboratory will look to see if you have a high-risk type of the virus. If high-risk HPV is found, the laboratory will test your sample for abnormal cell changes.  

But last year, a study we funded revealed a gap in many women’s understanding of HPV and its role in cervical screening, which could impact on how many people choose to attend their cervical screening appointments.  

  • Read more about the study  

3. 3- vs 5-year screening intervals  

In England and Northern Ireland, if you’re eligible for cervical screening you’ll be invited every 3 years. However, in Scotland and Wales, you may be invited every 5 years if you’re lower risk. So why the difference?  

In short, it’s thanks to research.  

In 2022, a study confirmed that offering cervical screening using HPV testing effectively prevents cervical cancer without the need for as regular screening.     

Alongside the results of previous research, the study showed that the time interval between cervical screens can be safely extended for those who test negative for HPV. Those who are higher risk will be invited more often . We’re hoping to see England and Norther n Ireland follow sui t.  

  • Read an explainer of the study  

YouScreen self-sampling kit

4. What are self-sampling tests?

We’ve already covered why cervical screening is so important, but we know that for some people, attending an appointment can have several barriers.

R esults from a first-of-its-kind study have revealed that around 50% of women eligible for cervical screening would prefer self-sampling, when the patient takes their own sample, over being tested by a clinician if they were offered information and a choice.  

This may be particularly important for those who have not attended cervical screening so far. HPV testing of self-collected samples may help to reduce inequalities in cervical screening uptake in specific groups of individuals, so what do we know about self-sampling?  

  • Get to grips with self-sampling  

 5. Preventing cervical cancer with vaccines

So, we know that HPV causes most cases of cervical cancer, and that we can test for HPV via screening. But, as you may know, there’s also a way we can protect against people getting HPV in the first place: vaccination.  

HPV vaccination has been offered in the UK since 2008, and in 2022, researchers we funded published a landmark study.   

The study found that the HPV vaccine was shown to dramatically reduce cervical cancer rates by almost 90% in women in their 20s who were offered it at ages 12 to 13.  

“It’s a huge achievement by lots and lots of people. It’s nice to think that this next generation will probably never really have to worry about cervical cancer in this country,” said Professor Peter Sasieni, who led the team at Kings College London.  

  • Read the full story of HPV and cervical cancer, and the development of the vaccine  

6. The vaccination of a generation

Globally, cervical cancer is the 4 th most common cancer in women.   

And despite studies like the one above showing that vaccination programmes reduce cervical cancer rates dramatically, there are still countries that don’t have universally accessible programmes.  

In the first series of our podcast , we heard from Dr Ishu Kataria, whose work into non-communicable diseases led her to work with the UN and WHO.   

She and her team are working out how to get the HPV vaccine to more than 70 million girls aged between 9 and 14 in India.  

  • Listen to the podcast  

If you want to learn more about cervical cancer, symptoms, screening, and treatments visit our About Cancer pages.    

Or, if you have questions about cancer, you can reach out to Cancer Research UK’s nurses on freephone 0808 800 4040 between 9am and 5pm Monday to Friday.  Alternatively, if you’d like to chat online with other people affected by cancer, you can join our fully moderated online community Cancer Chat at    

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Guest Blog: My Journey with Cervical Cancer

  • January 23, 2023

By Caroline Koller, Brand Communications Manager at HealthyWomen The work nonprofits do is nothing short of imperative, especially nonprofits that meet their audience where they’re at. I can attest to this personally. I was 26 and had recently finished extensive radiation and chemotherapy for advanced cervical cancer. Desperate to connect with others in my unique position, I began searching the web. I remember typing in “young woman’s cervical cancer story” and a HealthyWomen article popped up. It was a first-person article about a young woman who went through almost exactly what I did. She also battled to find a diagnosis, was diagnosed after the cancer had reached stage 3 and experienced the same complex emotions I was currently feeling. I cried my eyes out reading it and also felt an immense sense of relief and comradery. HealthyWomen met me exactly where I was with the resources I needed. It was healing. From there, I was a true fan of the brand — so much so, I joined the HealthyWomen team and now work in their communications department. January is Cervical Cancer Awareness Month, and I’m thankful to be able to share my story in hopes of helping other women. For six months, I spent nights lying on the floor with my legs propped up against the wall, which was the only position that seemed to give me some relief from the constant stabbing sensation radiating between my back and lower rectum. I had been living with pain and unexplained bleeding that was particularly heavy in the mornings and worsened during sex. It was hard to conceptualize living with symptoms like these every day. I was a vibrant woman with a jam-packed social life less than a year ago… Now I was isolating myself because I didn’t want to be a bother, complaining of my pain. During this time, I became a frequent Googler. I was always Googling my symptoms, mainly focused on trying to find forum-based, first-person articles of people who had experienced what I was experiencing. Reading real women’s stories was what I needed, what I was searching for. Once I read their stories, then I would turn to scientific resources. But what I was craving was just hearing I was not alone… After months of symptoms, I was diagnosed with stage 3C cervical cancer and immediately rushed into the flurry of what it’s like to try and beat this disease. During that process, I wanted all the information I could get, which isn’t how everyone is. I learned that some women want to only know the positives and some women, like myself, want to hear the good, bad, and ugly so that they can form a narrative on their own. This taught me that organizations that are there to help in these moments need to deeply understand the patient journey and the heaviness of information. They need to have a diverse range of materials that can cater to women at different stages of their journeys. For me, the information was validating, and I appreciated the nonprofits and organizations that made me feel this way. One night, in my NYC apartment, sitting on my bed after my first few days of being alone for the first time since entering treatment at Memorial Sloan Kettering Cancer Center, I found the HealthyWomen article that was exactly what I needed to read at that exact time. I remember sending it to my family, friends, and partner, explaining that this article would explain to them exactly how I was feeling — what it was like to go through what I was going through — and give them more context into what was going on in my head. After entering remission, I became a fierce advocate for women’s health. Working with HealthyWomen feels important because I know first-hand that the work that we’re doing is incredibly meaningful and there are women out there who need exactly what we’re creating. I try to keep that patient perspective top of mind with any project I work on. I encourage all the members and organizations of the National Health Council to do the same. What you’re doing is making a difference.

HealthyWomen is a member of the National Health Council. For more information on NHC membership, please email [email protected] .

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My journey with cervical cancer, during this time i was also getting quite large blood clots coming out when i was going to the toilet. the doctors decided to swab me and also gave me an internal and external ultrasound- the results to these all came back clear..

My journey with Cervical Cancer

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Research Papers:

Her2 as a novel therapeutic target for cervical cancer.

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Oncotarget. 2015; 6:36219-36230.

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Doo-Yi Oh , Seokhwi Kim , Yoon-La Choi , Young Jae Cho , Ensel Oh , Jung-Joo Choi , Kyungsoo Jung , Ji-Young Song , Suzie E. Ahn , Byoung-Gie Kim , Duk-Soo Bae , Woong-Yang Park , Jeong-Won Lee  _ and Sangyong Song

Doo-Yi Oh 1, 2, 3, * , Seokhwi Kim 1, * , Yoon-La Choi 1, 2, 3, * , Young Jae Cho 4, * , Ensel Oh 2, 3 , Jung-Joo Choi 4 , Kyungsoo Jung 3 , Ji-Young Song 2 , Suzie E. Ahn 2 , Byoung-Gie Kim 4 , Duk-Soo Bae 4 , Woong-Yang Park 3, 5 , Jeong-Won Lee 2, 3, 4, * , Sangyong Song 1, 2, *

1 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2 Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea

3 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea

4 Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

5 Samsung Genome Institute, Samsung Medical Center, Seoul, Korea

* These authors have contributed equally to this work

Correspondence to:

Jeong-Won Lee, e-mail: [email protected]

Sangyong Song, e-mail: [email protected]

Keywords: HER2, cervical cancer, targeted therapy, patient-derived xenograft, trastuzumab

Received: June 09, 2015      Accepted: September 11, 2015      Published: September 21, 2015

Surgery and radiation are the current standard treatments for cervical cancer. However, there is no effective therapy for metastatic or recurrent cases, necessitating the identification of therapeutic targets. In order to create preclinical models for screening potential therapeutic targets, we established 14 patient-derived xenograft (PDX) models of cervical cancers using subrenal implantation methods. Serially passaged PDX tumors retained the histopathologic and genomic features of the original tumors. Among the 9 molecularly profiled cervical cancer patient samples, a HER2 -amplified tumor was detected by array comparative genomic hybridization and targeted next-generation sequencing. We confirmed HER2 overexpression in the tumor and serially passaged PDX. Co-administration of trastuzumab and lapatinib in the HER2-overexpressed PDX significantly inhibited tumor growth compared to the control. Thus, we established histopathologically and genomically homologous PDX models of cervical cancer using subrenal implantation. Furthermore, we propose HER2 inhibitor-based therapy for HER2 -amplified cervical cancer refractory to conventional therapy.


Cervical cancer is the third most common cancer and fourth leading cause of death in women worldwide [ 1 ]. Radiotherapy and cisplatin-based chemo-radiation in addition to surgery are performed for curative treatment according to the clinical stage of the tumor and surgical findings [ 2 ]. However, patients with advanced or recurrent disease have a poor prognosis despite using of cisplatin-based combination chemotherapy [ 3 ]. Therefore, there is an increasing need for novel therapies that can replace or be added to the current therapy for these patients. Several targeted molecules including anti-vascular endothelial growth factor (VEGF) inhibitors, anti-epidermal growth factor receptor (EGFR) antibodies, and mammalian target of rapamycin (mTOR) inhibitors have been tested for recurrent cervical cancers, showing some promising results for certain patient subsets [ 4 ].

Xenografts derived from established cancer cell lines have been established but lack diverse histologic and molecular characteristics and tend to be derived from more aggressive tumors [ 5 ]. Unlike these cell line xenografts from cell lines, which cannot represent the complex tumor heterogeneity, xenografts using human cancer tissues mostly resolve these problems and adequately reflect the molecular features of patient tumors [ 6 ]. Patient-derived xenografts (PDXs) have been used for decades to screen for candidate drugs and monitor treatment response. Different models that vary according to tumor origin and implantation site are available. Several PDXs have been established for various cancers including colorectal cancer, bladder cancer, and glioblastoma [ 7 – 9 ]. However, cervical cancer PDXs have not so widely studied despite their potential benefits for drug testing and treatment response monitoring except one recent report using orthotopic model [ 10 ].

HER2 gene amplification or protein expression can be identified in various cancers other than breast; its incidence ranges from 1% to 12% in cervical cancers [ 11 , 12 ]. HER2 expression in cervical cancer has been reported to be present in recurrent tumors [ 13 ] and that its expression is related to poor prognosis in locally advanced cervical cancer [ 14 ]. Recent whole-exome sequencing studies provided evidence of HER2 activation by somatic mutation, amplification, and human papilloma virus (HPV) integration in cervical cancer [ 12 ], warranting investigation of the effects of HER2 inhibitors.

In this study, we tried to establish PDX using human cervical cancer tissues and find the new therapeutic strategy using this model. Here, we established PDXs derived from cervical cancer patients using subrenal capsule implantation models. In addition, when analyzing patient's tumors and PDXs, we found a single case with aberrant HER2 amplification and expression. Subsequent histopathologic and genomic characterization of the tumors in addition to monitoring response to anti-HER2 therapy in PDXs was performed. These results suggest that HER2 inhibitors-based therapy can be considered to on a platform that accurately mimics cervical cancer patients.

Establishment of cervical cancer PDXs

Clinicopathological characteristics.

Of the 21 patient samples implanted, 14 were successfully engrafted into mice to create PDX models (engraftment rate, 66.7%; Table 1 ). The patients’ ages ranged from 27 to 67 years (median, 49 years). Tumor samples were taken from the cervix of the radical hysterectomy specimens during surgery, except in 1 case (CX13) in which the sample was taken from lymph node tissue after excision because of recurrence in the inguinal lymph nodes. The HPV genotyping showed 19 samples were positive for HPV, all of which were high-risk types. Local recurrence was identified in 4 patients during routine follow-up. We did not find the difference of success rate according to histologic subtypes: squamous cell carcinoma (12/17, 70.6%) vs. adenocarcinoma (2/4, 50%).

Table 1: Clinicopathological characteristics of the cervical cancer patients and development of PDXs

patient journey cervical cancer

Histogenetic characteristics and similarities between patient's and PDX tissues

Histologic evaluation of the engrafted tumors was performed in 9 PDXs after the mice were sacrificed. A blinded review of histology of tumors from patients and PDXs was done by three pathologists (S S., YL C. and S K.). Microscopic examination revealed the retained histological characteristics of the tumors - either squamous cell carcinoma or endocervical adenocarcinoma - despite the passage of lineage ( Figure 1 ). Eight patient-PDX tumor pairs (CX4, 6, 8, 10, 11, 13, 15 and 17) showed histology of squamous cell carcinoma. Squamous cells with nuclear pleomorphism, intercellular bridges and relatively distinct cell borders were observed. Seven pairs were histologically graded as moderately differentiated squamous cell carcinoma, while one pair (CX11) were graded as poorly differentiated considering its profound nuclear pleomorphism and marked mitotic activity. Two pairs (CX6 and 15) were sub-classified as keratinizing type since they had abundant keratin pearls. Others were diagnosed as non-keratinizing type squamous cell carcinoma. There was a single pair showing histology of adenocarcinoma (CX14). Tumor cells architecturally forming relatively well-formed glands were observed in both patient and PDX tumors. However, a tendency to progress to poorly differentiated histologic characteristics was observed regardless of sample source as has been reported previously [ 5 ], suggesting that there is a clonal selection that divides actively to form a new tumor in the host nude mice toward more aggressive metastatic tumors. Tumor cells in PDX samples had more hyperchromatic nuclei with scanty cytoplasm. In CX14 PDX tumor (adenocarcinoma), tumor glands were more irregular in shape and situated back to back closely with little intervening stroma.

Histologic comparison between the patients and their PDX tumors.

Figure 1: Histologic comparison between the patients and their PDX tumors. Histologic analysis of the patient tumor samples (left panels) revealed eight were squamous cell carcinoma including both keratinizing and non-keratinizing types. The CX14 tumor sample was histologically endocervical adenocarcinoma (H&E, ×200). There was little difference between the histologic findings of the PDX tumor samples (right panels) and their corresponding patient samples.

We subsequently investigated whether the genomic features of the original tumors were retained by their PDX counterparts by using array comparative genomic hybridization (aCGH) and short tandem repeat (STR) analysis. The aCGH profiles demonstrated that all PDX tumors faithfully conserved the genomic DNA alterations observed in the corresponding patient tumors (Supplementary Figure S1). The STR profiles of 7 PDX counterparts (i.e., CX4-M1, CX8-M1, CX10-M1, CX11-M1, CX13-M1, CX15-M1, and CX17-M1) were identical to their respective original human tumors at all STR loci (Supplementary Table S2). To determine whether the genomic statuses of the PDXs were accurate and without cross-contamination, we performed a quality control testing for the xenografts. The mean Ct values for the human ALB were much lower than those for the mouse ALB for all 9 PDXs, indicating human DNA was much more abundant than mouse DNA in the PDX tumor tissues (data not shown).

Identification of aberrant HER2 amplification in one case of PDX model

We analyzed single nucleotide variations, copy number variation, and translocation with genomic DNA in all 9 cervical cancer patient samples using Cancer Panel, a targeted next-generation sequencing-based assay, which assessed all exons from 81 cancer-related genes and 31 introns from 5 genes recurrently rearranged in cancer. However, no significant targetable oncogenic genetic alterations were detected in our samples when we analyzed genes reported to be mutated in the COSMIC database ( ) (Supplementary Table S3). Interestingly, the Cancer Panel revealed a single case with HER2 amplification (Supplementary Table S3). We investigated whether the genetic features of the original tumors were retained by their CX17 PDX counterparts by using aCGH. Both PDXs and the original tumors exhibited conserved aCGH profiles including the HER2 amplicon localized on chromosome 17q21-22 in comparison to the other cases ( Figure 2A and 2B ).

HER2 amplification in a PDX (CX17).

Figure 2: HER2 amplification in a PDX (CX17). A. The recurrence of copy number alteration is plotted on the y-axis, and each probe is aligned along the x-axis in chromosomal order. Amplification of gene copy numbers are depicted in the black box ( HER2 ). Note the similarity between the genomic profiles of the original tumors and their PDX counterparts. B. Details of the array comparative genomic hybridization profile of the chromosome 17 amplicon containing the amplified HER2 oncogene comparing the original tumors and their PDX counterparts. Red dots represent gain and blue dots represent amplification for each probe aligned along the chromosome. The red arrows indicate HER2 amplification in chromosome 17.

Incidence of HER2 expression in human cervical cancers

To check the real proportion of HER2 expression in cervical cancer, we analyzed the Cancer Genomic Atlas database. We found that amplification and expression of HER2 was detected in 4 of the 183 available samples (2.1%; Figure 3A ). To confirm the protein expression in human cervical cancer, we performed immunohistochemistry in tissue microarray (TMA) composed with 412 human cervical cancer tissues. Among the 412 cases analyzed, 15 cases (3.6%) were scored 2+ and 3+ ( Figure 3B ). HER2 was predominantly expressed in the cell membrane and representative results of immunohistochemical staining are shown in Figure 3B .

Incidence of HER2 expression in human cervical cancers.

Figure 3: Incidence of HER2 expression in human cervical cancers. A. In order to better characterize the HER2, we analyzed a large ( N = 183) public microarray with the gene expression profiles (i.e., the Cancer Genomic Atlas) of cervical cancer patients. We investigated 4 cases with the highest HER2 expression levels that harbored HER2 amplification. Red and green dots indicate the centromere and HER2 , respectively. B. Frequency of HER2 expression in 412 cervical cancer patients (lower table). TMA core displaying membranous HER2 staining (From 0 to 3+) in 412 cervical cancer patients. score 0, no membrane reactivity; score 1+, group of tumor cells with weak or incomplete membrane reactivity; score 2+, group of tumor cells with weak to moderate membrane reactivity; score 3+, group of tumor cells with strong membrane reactivity. Scale bar = 200 μm.

To determine whether HER2 was amplified in other available cervical cancer cell lines (i.e., HeLa, SiHa, ME-180, MS751, and Caski), we analyzed the HER2 copy number by quantitative polymerase chain reaction (qPCR). Only the CX17 patient's tumor but not the cervical cancer cell lines exhibited a high HER2 copy number (Supplementary Figure S2). This suggests that only this PDX model can be used to investigate HER2-targeted therapeutics.

Analysis of a case of HER2 -amplified PDX

In the CX17 sample which exhibited HER2 amplification in the genomic study, the tumor was histologically defined as a stage IIB squamous cell carcinoma. The patient was a 52-year-old woman with a 7-cm mass in her cervix. She received radical hysterectomy followed by concurrent chemo-radiation therapy, and no recurrence was detected until the 21 month postoperative follow-up. qPCR showed that HER2 amplification was detected in CX17 case but not in CX10 ( Figure 4A ). HER2 amplification in CX17-M1 was also demonstrated by fluorescence in situ hybridization ( Figure 4B ) and silver in situ hybridization ( Figure 4C ), but not in CX10 which has no HER2 expression.

HER2 expression of CX17 PDX originating from the CX17 patient.

Figure 4: HER2 expression of CX17 PDX originating from the CX17 patient. A. Quantitative polymerase chain reaction (qPCR) gene copy number analysis to detect HER2 amplification. A breast cancer cell lines (SK-BR-3) was used as positive control to HER2 expression. B. Fluorescence in situ hybridization of HER2 revealed amplification in many tumor cells (red dots). C. Silver in situ hybridization of HER2 shows amplification of HER2 in CX17-M1 (black dots in upper panel). D. Quantitative reverse transcription PCR to identify HER2 expression in CX10, CX10 PDXs, and CX17 PDXs. E. HER2, phosphorylated HER2, and β-actin as a loading control were analyzed by western blotting. F. The tumor histology did not show any significant difference with serial passages in the HER2-staining areas (hematoxylin and eosin, ×200, upper panels). Immunohistochemistry for HER2 revealed the transition of expression from nuclear and cytoplasmic to membranous expression with serial passages (lower panels). (HER2, ×200).

To study the stability of the PDXs after serial transplantation, HER2 gene amplification and mRNA expression were analyzed in the serial passages and were compared with the expression profiles of the original tumors. HER2 gene amplification and mRNA expression remained very stable throughout sequential in vivo passages ( Figure 4A and 4D ). Moreover, HER2 expression was detected in CX17 PDX but not CX10 PDX according to western blotting and immunohistochemical staining results ( Figure 4E and 4F ). Although the tumors histologically showed few differences between the patient and serial passage samples on hematoxylin and eosin staining ( Figure 4F , upper panel), the HER2 immunohistochemical staining pattern and intensity exhibited dramatic differences. The patient's tumor sample showed mainly cytoplasmic and nuclear staining for HER2 with small portions of membranous staining; 70% of the total tumor volume was stained (intensity: strong, 30%; weak, 40%; Figure 4F , left panel). However, in the first PDX tumor (CX17-M1), 70% of the tumor cells showed positive membranous HER2 immunostaining (strong intensity) and the remaining 30% showed weak or moderate cytoplasmic staining. Furthermore, all tumor cells from 4 subsequent PDX passages (CX17-M2-M5) showed strong HER2 membranous positivity (>95%; Figure 4F , lower panel), suggesting the selection of HER2 -amplified clones had occurred with serial passages. HER2 immunohistochemical staining of the non-amplified case (CX10) showed weak cytoplasmic staining in both the patient sample and PDXs (Supplementary Figure S3). We also evaluated HER2 immunohistochemical positivity in 22 metastatic cervical cancer samples from patients (Supplementary Table S4). Among 22 metastatic samples, a single case that metastasized to the rectal wall 1 year after hysterectomy and subsequently to the colon exhibited HER2 positivity on immunohistochemical staining; 20% of the tumor cells in both metastatic samples were positive, showing a membranous staining pattern (Supplementary Figure S4). These results support the possibility of the clinical application of HER2 inhibitors for cervical cancer treatment.

Efficacy of anti-EGFR therapy in a HER2 -amplified PDX

To assess the validity of HER2 as a therapeutic target in HER2 -amplified cervical cancer, we used the CX17 PDX to evaluate the efficacy of 2 HER2 inhibitors by analyzing the inhibition of tumor growth. Trastuzumab and lapatinib are US Federal Drug Administration-approved HER2-inhibitors widely used to treat HER2 -amplified breast cancers [ 15 ]. Compared to the untreated tumors, the combination of trastuzumab and lapatinib significantly reduced tumor weight (−50%; * P = 0.013; Figure 5A – 5C ). Moreover, trastuzumab and lapatinib combination decreased the phosphorylation of mitogen-activated protein kinase (Phospho-p42/44 MAPK [Thr202/Tyr204]) and STAT3 (Phospho-Stat3 [Tyr705]), but not AKT (Phospho-AKT [Ser473]) in the CX17 PDX ( Figure 5D ) [ 16 ].

Effect of dual HER2 inhibitors administration on tumor growth in CX17 PDX.

Figure 5: Effect of dual HER2 inhibitors administration on tumor growth in CX17 PDX. A. Schematic that illustrates the CX17 PDX experimental design. B. Female BALB/c nude mice bearing the CX17 tumor tissue received the vehicle control ( N = 10) or a combination of 10 mg/kg trastuzumab 2 days per week and 100 mg/kg lapatinib daily ( N = 10) as indicated. * P = 0.013. C. Images of tumors from mice treated with the vehicle control or a combination of trastuzumab and lapatinib. In each picture, the small left piece is the normal kidney (i.e., no tumor transplanted), and the large right one is the developed PDX. D. Western blot analysis results with the indicated antibodies of representative tumors tissues taken after sacrifice (CX17 PDXs).

In this study, we established histopathologically and genomically homologous PDX models for human cervical cancer and found a single case with aberrant HER2 amplification and expression. Subsequent histopathologic and genomic characterization of the tumors in addition to monitoring response to anti-HER2 therapy in PDXs was performed. These results strongly suggest that the dual administration of a HER2 small-molecule inhibitor and a monoclonal antibody directed against the HER2/neu receptor is beneficial for the treatment of HER2 -amplified cervical cancer in clinical settings.

Orthotopic tumor implantation may also confer a translational advantage, as the tumor develops in the same anatomic microenvironment [ 17 ]. However, the generation of orthoxenografts is more labor intensive and expensive, requires complex surgery, and often requires imaging methods to monitor tumor growth [ 18 ]. Meanwhile, tumor implantation in the subrenal capsule yields an impressive engraftment success rate and requires a simple surgery, which is one of the most important variables for studies seeking to implement real-time PDX data for personalized cancer treatment [ 5 ]. Although a heterotopic cervical cancer PDX models are useful for preclinical evaluation of personalized medicine, they are still limitations in translational cancer research. Heterotopic sites in the subcutaneous flank, mammary fat pad, and sub-renal capsule may lack the same microenvironment seen in the orthotopic sites within the ovary or peritoneum [ 19 ]. However, we first established cervical cancer PDX model with the higher subrenal capsule engraftment rate, low cost, recapitulating patient clinicopathologic features, tumor histology, and genomic characterization for at least 8 passages. To date, cervical cancer PDXs using subrenal implantation have not so studied despite their potential benefits for drug testing and treatment response monitoring. Hiroshima et al . [ 10 ] identified that the orthotopic model of cervical cancer, but not subcutaneous implantation mimics the patient metastatic pattern. The point is whether our cervical cancer PDX models reflect the patient metastatic pattern. Many papers identified that subrenal implantation model proved to be a suitable model to follow the metastatic process in prostate, renal, and colon cancer [ 20 – 22 ], suggesting that our cervical cancer PDX models would be suitable to mimic not only in vivo tumorigenicity, but also the metastatic pattern than other heterotopic PDX model. Thus, the present results support the value of cervical cancer PDXs using subrenal implantation for preclinically predicting drug responses.

In contrast to breast cancer, the prognostic value of HER2 in cervical cancer remains controversial. HER2 was associated with poor prognosis in 126 cervical cancer patients with stage IB/IIA disease and good prognosis in 55 cervical cancer patients with stages I–IVA disease [ 4 ]. HER2 was amplified in a small percentage (2.1%) of genetically unselected cervical cancers from the Cancer Genomic Atlas database and its protein overexpression was 3.6% of cervical cancer patients in tissue microarray samples ( Figure 3 ). These results are supported by work recently published by Ojesina et al . [ 12 ], who observed HER2 amplification in a small percentage of cervical cancer patients and evidence of HER2 activation by somatic mutation, amplification, and human papilloma virus (HPV) integration in cervical cancer. One of our patient samples exhibited HER2 amplification, which was progressively enriched with serial passages. Although absolute numbers remain small, it is evident that some cases with HER2 amplification either in cervical cancer PDXs or in patients will not respond to chemo-radiation. Another interesting result is the transition of nuclear and cytoplasmic HER2 expression to membranous expression with serial passages of the tumors in cervical cancer PDXs. Some reports indicate HER2-negative cervical cancers transform into HER2-expressing ones when they recur or metastasize [ 13 , 23 ]; this transition of the HER2 tumor immunoprofile could be a therapeutic target. In one case report, a HER2-negative cervical cancer exhibited HER2 positivity after peritoneal metastasis; the patient had undergone combined trastuzumab and lapatinib treatment, and follow-up imaging revealed a dramatic treatment response [ 11 ]. There are two possible explanations for the transition of HER2 expression. First, a minor tumor clone originally expressing HER2 has a selective advantage with serial passages. One study indicates HER2-positive cells may have a selective advantage over HER2-negative cells both in vitro and in vivo [ 24 ]. Second, tumor cells previously not expressing HER2 began expressing HER2 after serial passaging. Some colon cancer cases exhibit cytoplasmic HER2 overexpression as was found in a patient tumor sample (CX17) in this study [ 25 ]. The accumulated HER2 protein in the cytoplasm can migrate to the membrane under the influence of the unfolded protein response [ 26 ]. In breast cancer, 6% of HER2-negative primary tumors convert to HER2-expressing tumors during metastasis [ 27 ]. However, as our molecular data show increases in HER2 DNA, mRNA, and protein, it can be concluded that a HER2 -amplified clone proliferated with serial passaging in the PDXs.

To date, we can find only one clinical study in cervical cancer patients to evaluate the therapeutic effects of anti-HER2/neu therapy. Monk et al . reported that only pazopanib alone improved progression-free survival, whereas the combination of lapatinib and pazopanib was not effective [ 28 ]. However, HER2 -positive and HER2 -negative patient groups were not classified, and HER2 inhibitors were administered to all advanced-stage cervical cancer patients. It is doubtful any patients with HER2 -amplified cervical cancer had the potential to benefit from HER2-targeted therapy. In this study, we used a dual therapy with trastuzumab and lapatinib instead of anti-HER2 monotherapy. Previously, we found that no significant inhibition of CX17 PDX tumor growth was observed following treatment with trastuzumab or lapatinib alone compared to the vehicle-treated controls (data not shown). Moreover, treatment with trastuzumab alone down-regulated HER2 receptor expression (Supplementary Figure S5), suggesting trastuzumab-mediated HER2 receptor degradation may be the key to resistance acquisition, which inevitably occurs in HER2 -amplified cervical cancer. The results of Scaltriti [ 16 ] and this study show that trastuzumab can down-regulate HER2 receptor, whereas the tyrosine kinase inhibitor, lapatinib, induces HER2 accumulation at the cell surface (Supplementary Figure S5). These results confirm trastuzumab alone may be not as effective as trastuzumab and lapatinib combination therapy in HER2 -amplified cervical cancer. Moreover, Lapatinib in combination with trastuzumab to HER2-overexpressing breast cancer cells SKBR3 and MCF7-HER2, inhibited mitogen-activated protein kinase (MAPK) phosphorylation and in vitro and in vivo tumor growth [ 16 ], suggesting that a mechanism of action of the combination may be clinically relevant and exploitable in the therapy of patients with HER2-positive tumors. Although we checked the effect of 2 HER2 inhibitors on tumor growth in vivo in HER2-overexpressed cervical cancer PDX models, since our cervical cancer PDX is treatment naïve, we suggest that cervical cancer PDXs would respond to cisplatin-based chemotherapy or radiation therapy. Assuming cervical cancer PDXs accurately mimic the human situation, the tumor regression produced by trastuzumab and lapatinib combination therapy demonstrates the potential benefit of this therapeutic regimen if evaluated in clinical trials.

Currently, there are no clinical trials registered to examine dual anti-HER2 therapies in HER2 -amplified cervical cancer. The preclinical data reported herein suggest combination therapy with trastuzumab and lapatinib induces significant in vivo anti-tumor activity and overcomes the potential for cervical cancer to harbor trastuzumab resistance induced by treatment with trastuzumab alone. Furthermore, our preclinical findings in HER2 -amplified cervical cancer PDX models may accurately predict the outcomes and treatment response of cervical cancer patients.


Patient tissue samples.

The tumor samples from patients with cervical cancer were taken from fresh surgical specimens immediately after radical hysterectomy and lymph node dissection. All patients provided informed consent, and the study was conducted with institutional review board approval (IRB File No. 2009-09002). The patients’ clinical information was obtained from medical records, including age, menopausal status, history of neoadjuvant or adjuvant therapy, and disease-free survival. The patients were followed up every 3 months, and examinations included a Pap smear and blood test for tumor markers (TA-4) in addition to imaging studies including magnetic resonance imaging and positron emission tomography to detect disease progression.

The HeLa, SiHa, ME-180, MS751, Caski, and SK-BR-3 ( HER2 -amplified breast cancer) cell lines were obtained from the American Type Culture Collection (Rockville, MD, USA) and maintained in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum and Dulbecco's modified Eagle's medium/Ham F12 1:1 (DMEM/F12) supplemented with 10% fetal bovine serum at 37°C in 5% CO 2 . All of the cell lines used were authenticated via short tandem repeat (STR) profiling before beginning a new series of experiments, and kept in culture for <3 months.

Establishment of PDXs

Female BALB/c nude mice were purchased from ORIENT BIO (Sungnam, Korea). The tumor samples were collected after surgery and cut into 1-mm 3 pieces in phosphate-buffered saline. Subrenal capsule xenografts were made from the human cervical tumor tissues grafted underneath the renal capsules of female BALB/c nude mice ( N = 5 per tumor sample) as described previously [ 29 ]. When the tumors appeared about 2 cm at the graft site or mice became moribund after grafting, the mice were euthanized and the tumors were collected; these samples were considered tumorigenic and designated “M1”. Tumorigenic samples were serially passaged in vivo to make “M2” PDX tumors. Tumor tissue samples were stored in liquid nitrogen. This study was approved by the Institutional Animal Care and Use Committee of the Samsung Biomedical Research Institute, which is an accredited facility of the Association for Assessment and Accreditation of Laboratory Animal Care International (protocol No. H-A9-003) and abides by the Institute of Laboratory Animal Resources Guide.

HPV genotyping

A polymerase chain reaction (PCR)-based HPV DNA microarray was performed for all 21 patients’ tumor samples in formalin-fixed paraffin-embedded blocks by using a DNA chip (Biometrix Technology Inc., Chuncheon, South Korea) according to the manufacturer's instructions; 15 high-risk HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68) and 9 low-risk HPV types (HPV 6, 11, 34, 40, 42, 43, 44, 54, and 70) were detected [ 30 ].

Histologic examination and immunohistochemistry

Hematoxylin and eosin (H&E) staining was performed on all paraffin blocks from the tissue samples obtained both from patients and PDXs. The PATHWAY ® anti-HER2/neu (4B5; Roche, Basel, Switzerland) antibody was used for HER2 immunohistochemical staining. Tissue sections (3 mm) were deparaffinized and rehydrated, and antigen retrieval was performed for 40 min in citrate buffer (pH 6.1) at 95°C. Diaminobenzidine was used as the chromogen, and the sections were counterstained with hematoxylin. The BenchMark XT automated slide processing system (Ventana Medical Systems, Tucson, AZ, USA) was utilized. HER2-expressing breast cancer tissues were used as a positive control.

Array comparative genomic hybridization

Array comparative genomic hybridization was used to detect genetic variation in the form of deletions and duplications. An Agilent human whole-genome comparative genomic hybridization 8 × 60 K microarray platform from Agilent Technologies (Santa Clara, CA, USA) was utilized. Tumor and control DNA were labeled with Cy5-dCTP and Cy3-dCTP, respectively, followed by DNA hybridization to a microarray. All slides were scanned on an Agilent DNA microarray scanner. Data were extracted from scanned images with Agilent CGH Analytic Version 6.5 software using the ADM-2 statistical algorithms with 6.0 sensitivity thresholds. Signal intensities were normalized by comparing the tumor samples with normal male genomic DNA (Promega, G147A) and subsequently analyzed as described previously [ 9 ].

Short tandem repeat analysis

For STR genotyping, target DNA was amplified by multiplex PCR for 16 loci using the AmpFlSTR Identifier PCR Amplification Kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturer's instructions. PCR products mixed with an internal size standard (GS-500 LIZ; Applied Biosystems) were electrophoresed on an ABI 3130xL Genetic Analyzer (Applied Biosystems) and analyzed with GeneMapper 4.0 software using the supplied allelic ladders (Applied Biosystems).

Mutation analysis using the cancer panel

The Cancer Panel is a targeted next-generation sequencing assay that was developed, validated, and provided by the Samsung Genome Institute (Samsung Medical Center, Seoul, Korea); it includes all exons from 81 cancer-related genes and 31 introns from 5 genes recurrently rearranged in cancer. Using the Illumina HiSeq 2500 instrument, the captured libraries underwent paired-end high-depth sequencing (target > 800 × coverage). Data were analyzed using an automated bioinformatic pipeline designed to detect various genetic alterations including single nucleotide variations, insertion and deletion, gene amplification and deletion, and gene fusions.

Quantitative real-time and quantitative reverse-transcription polymerase chain reaction

HER2 copy number amplification was performed with a PRISM 7900HT Fast Realtime PCR system (Applied Biosystems). The primer sequences are provided in supplementary Table S1. All reactions were performed in triplicate. The PCR program was as follows: preheating at 50°C for 2 min; 95°C for 10 min; 40 cycles at 95°C for 15 s and 60°C for 1 min; and 1 cycle for melting curve analysis. RNA isolation and cDNA synthesis were performed using the RNeasy Mini Kit (Qiagen, Valencia, CA, USA) and SuperScriptIII first-strand kit (Invitrogen, Waltham, MA, USA) according to the manufacturers’ instructions. The HeLa cell line, which is a HER2-negative cervical cancer cell line, was used as a calibrator for the relative quantification of HER2 expression level. The calculation equation and PCR protocol were the same as those used for copy number analysis.

HER2 in situ hybridization

Silver in situ hybridization (SISH) was performed according to the manufacturer's protocols. Sequential in situ hybridization procedures for HER2 and CEN17 signal detection were conducted with the INFORM HER2 DNA, and CEN17 probes (Ventana Medical Systems). The Ventana ultraView SISH Detection Kit on a Ventana BenchMark XT automated slide stainer was also utilized according to the manufacturer's instructions. Fluorescence in situ hybridization was performed using dual-color DNA-specific probes from PathVysion™ (LSI ® HER2 Spectrum Orange™ and CEP17 Spectrum Green™; Abbott, San Francisco, CA, USA).

Tissue microarray construction

H&E-stained slides of cervical cancer were reviewed and the appropriate tumor area was marked. The corresponding paraffin block was retrieved and the marked areas were matched. The cores of tumor areas were manually punched using a precision instrument (Labro TMA kit) and embedded into the recipient block with 60 microholes (diameter, 2 mm; depth, 5 mm). The microarray blocks were heated at 60°C for 30 min.

Western blotting

Immunoblotting was performed using antibodies against the following: HER2 (Cell Signaling Technology, 2165), p42/44 MAPK (Cell Signaling Technology, 9102), Phospho-p42/44 MAPK (Thr202/Tyr204; Cell Signaling Technology, 4370), AKT (Cell Signaling Technology, 9272), Phospho-AKT (Ser473; Cell Signaling Technology, 9271), STAT3 (Cell Signaling Technology, 4904), Phospho-STAT3 (Tyr705; Cell Signaling Technology, 9145), β-actin (Santa Cruz, sc-47778), GAPDH (Santa Cruz, sc-25778), and anti-HER2 (phosphor Y877; Abcam, ab108371).

HER2-targeted therapy

Tumor tissue from the CX17 patient was obtained following surgery and implanted underneath the renal capsules of female BALB/c nude mice as described above. After engraftment and tumor mass formation, the tumors were passaged and expanded by 5 generations (M5) with 2 cohorts each consisting of 10 mices. After implantation (8 weeks), the established tumors ( N = 10 for each tumor sample) were treated with the following regimens: trastuzumab (Roche Genentech, San Francisco, CA, USA) 10 mg/kg twice weekly and lapatinib (LC Laboratories, Woburn, MA, USA) 100 mg/kg daily. After 3 weeks of treatment, the tumors grown under the subrenal capsule were harvested and weighed.

Statistical analysis

The Mann–Whitney U test was used to evaluate the significances to compare differences among the groups for in vivo assay. All statistical tests were two-sided, and P values less than 0.05 were considered to be statistically. SPSS software (version 17.0; SPSS, Chicago, USA) was used for all statistical analyses.


This study was supported by a Korea Health Technology R&D Project grant from the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3418 and HI14C1940), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2013612), and a grant (SP2B20222 and SMX1132711) from the Samsung Biomedical Research Institute.


The authors declare that there are no conflicts of interest.

Editorial note

This paper has been accepted based in part on peer-review conducted by another journal and the authors’ response and revisions as well as expedited peer-review in Oncotarget.

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  • v.18(2); 2023 Feb

Circulating cervical cancer biomarkers potentially useful in medical attention (Review)

Ruth ruiz esparza garrido.

1 Investigadora por México, Non-coding RNAs Laboratory, Medical Research Unit in Human Genetics, Children's Hospital ‘Dr. Silvestre Frenk Freund’, National Medical Center XXI Century, Mexican Institute of Social (Instituto Mexicano del Seguro Social, IMSS), Doctores, Mexico City 06720, Mexico

Mercedes Gutiérrez

3 ATSO PHARMA Laboratory, Jardines del Pedregal, Álvaro Obregón, Mexico City 01900, Mexico

Miguel Ángel Velázquez Flores

2 Non-coding RNAs Laboratory, Medical Research Unit in Human Genetics, Children's Hospital ‘Dr. Silvestre Frenk Freund’, National Medical Center XXI Century, Mexican Institute of Social (Instituto Mexicano del Seguro Social, IMSS), Doctores, Mexico City 06720, Mexico

Associated Data

Not applicable.

Cervical cancer (CC) is a public health problem worldwide, including Mexico. This type of cancer is the fourth most frequent in women worldwide; in Mexico it is the second most common type in women after breast cancer. The diagnosis of CC is based mainly on Pap smears and colposcopy and the identification of molecular tools that serve as a support for these methods is urgent. Regarding this, differential expressions of specific circulating biomolecules has been detected and, based on this, they have been postulated as potential biomarkers for CC diagnosis, prognosis, and/or to identify the response to treatments. Importantly, the combined analysis of these molecules considerably improves their efficacy as biomarkers and their potential use in the medical attention is promising.

1. Introduction

Cervical cancer (CC) is the four most common cancer in women with an estimate of 604,000 new cases and 342,000 deaths per year worldwide ( 1 ). Most of the new cases (85%) and deaths (90%) occur in low- and middle-income countries, where CC is the third most common cancer among women. According to GLOBOCAN 2020, CC is the second most common cancer in Mexico with 9,439 new cases and 4,335 deaths per year. The Federation of Gynecology and Obstetrics (FIGO) staging system classifies CC in four stages, I-IV, which in turn are subdivided in various subtypes; this classification is mainly based on surgery, pathologic analysis and imaging ( 2 ).

The expression of certain circulating biomolecules is modified when a disease is established, having a great potential to detect and predict the disease as well as to identify the response to different treatments ( 3-5 ). For CC, there are several studies showing biomolecules, proteins, non-coding RNAs (ncRNAs), and circulating DNA (cDNA) with a great potential to be useful biomarkers for diagnosis, prognosis, and to determine the response to treatments currently used in medical attention for CC. Although certain of these protein biomarkers may also function as biomarkers for other HPV-related cancers, previous studies showed that the combined use of these molecules increases their potential as biomarkers for this disease ( 6-8 ). Although these biomarkers have a sensitivity very similar to that of colposcopy and p16 ( Table I ) ( 9-29 ), a significant advantage is that it is a minimally invasive methodology, having a very important impact on the number of women who would be screened with this test. The aim of the present study was to review the literature related to these potential biomarkers, emphasizing improved results as biomarkers when these molecules have been analyzed in combination.

Comparison of sensitivity and specificity among biomarkers and other CC detection methods.

The information was searched in Pubmed and in academic Google. The criteria followed to search the literature were the following: Circulating biomarkers, CC, ncRNAs and cDNA. In addition, biomarkers for HPV-associated cancers and public spending in Mexico for the treatment of CC were searched. The inclusion criterion was full access to the reviewed articles. Those articles that could not be accessed were excluded from the review.

2. Proteins

The search of circulating proteins as potential biomarkers in pathologies such as cancer has been addressed for several decades. The objective is clear, to diagnose and monitor the diverse types of cancer in a minimally invasive way; however, this search has not been easy and even when there are proteins currently used in the medical attention, their sensitivity (the ability to detect a disease in patients in whom the disease is actually present) and specificity (the ability to rule out the disease in patients in whom the disease is actually absent) is relatively low ( 9 ). To date, the most common circulating cancer marker proteins used in medical attention for distinct types of cancer are: i) The squamous cell carcinoma antigen (SCC-A), ii) The carcinoembryonic antigen (CEA), iii) The α-fetoprotein, iv) The β-subunit of human chorionic gonadotropin, v) Lactate dehydrogenase and vi) The cancer antigen 125( 10 ). Regarding CC, massive analyses have revealed groups of circulating proteins differentially expressed in this disease with a great potential to be used as biomarkers. Notably, the use of two or more of these proteins has been revealed to considerably increase their sensitivity and specificity ( Table II ) ( 30 , 31 ).

Circulating proteins as potential biomarkers for cervical cancer.

X: The corresponding biomarker is useful for the stated purpose. SCC, squamous cell carcinoma; CEA, carcinoembryogenic antigen; CA-125; HMGB1, high mobility group box chromosomal protein 1; CTHRC1, collagen triple helix repeat containing 1; M-CSF, macrophage-colony stimulating factor; VEGF, vascular endothelial growth factor; PIGF, placental growth factor.

In the 1970s, the SCC-A was identified by using the hybridoma technique in SCC of human uterine cervix ( 11 ). SCC-A is a serpin that comprises two nearly identical proteins (45 kDa), SCC-1 and SCC-2, which possess unique proteinase inhibitory properties ( 10 , 11 ). SCC-1 exerts an anti-apoptotic action through the inhibition of chymotrypsin and cathepsin L. The mechanism of protection of tumor cells from apoptosis involves the inhibition of the caspase-3 activity and/or upstream proteases. SCC-2 inhibits cathepsin G and mast cell chymase, thus protecting epithelial cells from these proteases-induced inflammation ( 32 ).

Increased serum SCC-A levels were observed in more advanced SCC stages (in 28-88% of the patients) allowing the use of SCC-A as diagnostic and prognostic biomarker for this cancer subtype ( 30-32 ). Differences in the percentage of SCC-A detection were attributed to various factors, such as the histological grade and the cutoff in the SCC-A serum concentration. Although numerous years have passed since its discovery, the clinical use of SCC-A remains under debate, for the increase on its expression has been reported in patients with SCC of the esophagus, lung, head, neck, and in anal canal and uterine cervix, as well as in patients with several non-malignant skin lesions, such as pemphigus and renal failure. Regarding this, the exposure to TNF-α significantly increased the production of SCC-A in normal human epidermal keratinocytes ( 33 ).

In addition to SCC-A, other potential circulating biomarkers have been identified. Mitsuhashi et al ( 21 ) described that the serum YKL-40 level was elevated in both SCC and adenocarcinoma. YLK-40 is a glycoprotein member of the glycosyl hydrolase 18 family; it is secreted by active macrophages, chondrocytes, neutrophils and synovial cells. Recent studies suggested that YLK-40 plays a role in the inflammation process and tissue remodeling ( 34-36 ). This molecule appears to be a favorable CC biomarker in both SSC and adenocarcinoma subtypes, and it appears to be more specific than SCC-A and CA125. Previous findings demonstrated that serum YKL-40 level is increased in several solid tumors with a variety of histological types ( 37 , 38 ). This protein is a biomarker associated with inflammation and, despite this, it could be a correlation between the C-reactive protein (CRP) and YKL-40( 39 ). YKL-40 serum appears to be more a non-specific biomarker of inflammation, since its expression was higher than that of CRP, allowing to discriminate patients with CC from tumor-free individuals. In addition, YKL-40 appears to be an improved serum biomarker for adenocarcinomas detection than CA-125 exhibiting 78 and 68% sensitivity for all grades and for stage I tumors, respectively ( 21 ). Although it does not appear to be an ideal biomarker due to its relative low sensitivity to detect CC, the receiver operating characteristic (ROC) and area under a ROC curve (AUC) analysis revealed that YKL-40 discriminates healthy individuals from patients with CC. Similarly, the YKL-40 levels were identified to be a poor prognostic variable for relapse of the disease ( 40 ).

Sheng et al ( 41 ) examined the clinical value of serum high mobility group box chromosomal protein 1 (HMGB1) levels in the early diagnosis of recurrent cervical SCC and compared them with the values obtained for SCC-A, cytokeratin fragment 21-1 (CYFRA) and CEA. HMGSB1 is a nuclear DNA-binding protein able to regulate transcription and is involved in organization of DNA, playing a role in several cellular processes including inflammation, cell differentiation and tumor cell migration. In the present study, serum HMGB1 levels-in patients with recurrent CSCC-were significantly higher than in patients with non-recurrent disease and healthy controls. The combination of the HMGB1 expression with other biomarkers such as SCCA, CYFRA21-1 and CEA increased the sensitivity of HMGB1 to detect CC and serial combinations of these markers also increased the specificity. Relatively high serum expression levels of HMGB1 were inversely correlated with disease-free survival and overall survival.

A proteomic screening carried out by Chen et al ( 42 ) in 10 healthy control women and 39 patients with CC, before and after surgery, identified three peptide biomarkers, distinguishing patients with CC from individuals without cancer as well as preoperative patients with CC from those who had already been subjected to surgery. TKT and FGA peptides were upregulated in CC and preoperative patients, whereas the APOA1 peptide region was downregulated. Meanwhile, collagen triple helix repeat containing 1 (CTHRC1), a protein that may play a role in the cellular response to arterial injury through the involvement in vascular remodeling, was evaluated as another potential serum marker for CC detection, particularly for SCC. Xu et al ( 22 ) studied the CTHRC1 expression in three different groups [individuals without cancer, SCC, and cervical intraepithelial lesions (CIN)], demonstrating its overexpression in SCC relative to CIN and individuals without cancer. The ROC curve showed an AUC value for CTHRC1 and SCC-Ag of 0.665±0.034, and 0.878±0.027 respectively; the sensitivity and specificity for these biomarkers were 57 and 85% (CTHRC1), and 78 and 86% (SCC-Ag), respectively. Importantly, the combined analysis of CTHRC1 and SCC-Ag considerably increased the AUC value (0.879±0.027) and the sensitivity (87%) and specificity (84%). The aforementioned study strongly suggested the potential use of CTHRC1 as a novel prognostic and metastatic biomarker for SCC, whose potential as a biomarker increased considerably when combined with SCC.

It is well documented that activation of Macrophage-Colony Stimulating Factor (M-CSF) and vascular endothelial growth factor (VEGF) is involved in the pathogenesis and spread of distinct types of cancer, including CC. Regarding this, Sidorkiewicz et al ( 24 ) examined the M-CSF and VEGF plasma levels and compared them with those of CA-125 and SCC-A in three groups of patients: i) The CC group (patients with either SCC or adenocarcinoma), ii) The cervical dysplasia group and iii) The control group. The median levels of M-CSF and VEGF as well as those of CA-125 and SCC-A were significantly different in the three groups relative to the control group. The sensitivity and specificity for VEGF and SCC-Ag were of 82 and 76%, and 81 and 74%, respectively. In the adenocarcinoma group, the VEGF sensitivity and specificity were respectively of 87 and 76% ( 24 ). The results indicated a possible clinical applicability for these proteins and a relatively high diagnostic power for the M-CSF, VEGF, CA-125 and SCC-Ag combination. Similarly, the combined analysis of α-Actinin 4 (ACTN4) and SSC-A is a promising serological examination for CC detection. ACTN4 plays an essential role in regulating cellular signaling pathways correlated with various types of cancer progression and poor patient prognosis, involved in the invasion and metastasis of colorectal, pancreatic and ovarian cancer. Its principal function is by regulating cell invasion due to its participation in the epithelial-to-mesenchymal transition; however, it is also involved in controlling the cancer stem cell properties and chemoresistance in CC. Zhu et al ( 43 ) demonstrated the circulating and tumor ACTN4 overexpression in patients with CIN3 or more advanced stages. In addition, the ACTN4 mRNA was also overexpressed in CC tissues and in tissues with advanced FIGO stages, larger tumor sizes, and positive lymph node metastasis. In conclusion, ACTN4, in combination with SCC-Ag, is a potential biomarker for the diagnosis and prognosis of patients with CIN3 or more advanced stages.

Yang et al ( 23 ) proposed that circulating placental growth factor (PIGF) and its receptor VEGFR-1 (Flt-1) can serve as possible valuable diagnostic biomarkers for CC, and their combined use increased the potential to diagnose patients with early CC. A total of 44 preoperative patients with CC, 18 cases with CIN, and 20 controls were studied and both PlGF and Flt-1 were significantly increased in the CC group when compared with that with CIN or without cancer. PlGF presented a relatively high power to detect CC with a 61% sensitivity and an 89% specificity; meanwhile, Flt-1 showed a 50% sensitivity and a 92.11% specificity. Remarkably, the combined use of PlGF and Flt-1 increased the CC diagnosis (sensitivity of 70% and specificity of 92%) ( 23 ).

Summarizing, different circulating proteins are differentially expressed in patients with CC relative to individuals without cancer, having a great potential to be used in clinical diagnosis and even more when two or more proteins are analyzed in a combined manner. Importantly, not only circulating proteins have been identified as biomarkers for CC but also microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), as well as cDNA.

ncRNAs are RNA molecules, which are not translated into a protein, including transfer RNAs, ribosomal RNAs, small non-coding RNAs (snRNAs) and lncRNAs ( 44 ). snRNAs and lncRNAs regulate numerous biological functions and their expression is finely regulated at different stages of development of organisms to fulfill very particular functions ( 45 , 46 ). Numerous lines of evidence indicate their involvement in cancer, specifically in CC, and their differential expression, mainly in blood, has been related to diagnosis, prognosis, and treatment response of patients with CC, as described below.

MiRNAs are snRNAs of 18-34 and 80-100 nucleotides (nt) ( 47-49 ) in size, which control gene expression by inhibiting protein translation, by regulating gene transcription and the expression and/or the function of lncRNAs ( 50-52 ). Notably, circulating miRNAs act as Toll-receptors ligands to activate intracellular signaling pathways resulting in the control of cellular response in other organs and tissues ( 53 ).

To date, numerous circulating miRNAs have been identified as possible biomarkers for low-grade squamous intraepithelial lesions (LSIL), CIN and CC and most of them demonstrate higher AUC values and a higher sensitivity and specificity than proteins. Notably, both sensitivity and specificity to detect CC by miRNAs is relatively high and they were considerably increased when analyzed in combination ( 6-8 , 54-72 ) ( Fig. 1 , Fig. 2 and Fig. 3 ). The majority of miRNAs have the potential to be biomarkers for CIN and CC diagnosis and only certain for prognosis ( Fig. 3 ). MiRs 34a and 218 are particularly important, since they allow to distinguish LSIL and CC HPV16 + from healthy women ( 60 ) ( Fig. 1 ). Their clinical use in LSIL detection-in a minimally invasive form-would have a huge impact on public health in countries where CC remains a public health problem, such as Mexico.

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Upregulated miRNAs. These group of miRNAs have the potential to be biomarkers to distinguish CIN, LGCLs or CC from the controls. MiRs 18 and 17-5p showed the highest sensitivity for CC diagnosis (˜95%). LGCLs, low-grade cervical lesions; CIN, cervical intraepithelial lesions; CC, cervical cancer; miRNA or miR, microRNA.

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Downregulated miRNAs. miR-651 showed the highest AUC value to detect CC and it was also positively correlated with cisplatin resistance. Meanwhile, miR-638 had a very high sensitivity for CSSC diagnosis, but only when its expression was analyzed with that of SCC. miRNA or miR, microRNA; AUC, area under the curve; CC, cervical cancer; CSCC, cervical squamous cell carcinoma.

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Combined miRNAs analysis. The combined analysis of the miRNAs expression showed their potential use to diagnose CIN and CC, as well as to CC prognosis and to determine the response to treatments of patients. Importantly, the combination of two or more miRNAs considerably increases the sensitivity and specificity to detect and/or predict the response of patients to treatments. miRNA or miR, microRNA; CIN, cervical intraepithelial lesions; CC, cervical cancer; AUC, area under the curve.

A very interesting study showed the miR-221-3p enrichment in exosomes, which were secreted by CSCC and captured by human lymphatic endothelial cells (HLECs), resulted in their migration promotion, tube formation, lymphanogenesis induction and LN metastasis in CSCC patients. These processes appear to be regulated, at least partly, by targeting vasohibin-1, leading to the ERK/AKT pathway activation in HLECs ( 65 ).

To date, there are several circulating miRNAs that can be used for the LSIL, CIN and CC diagnosis and certain of them are specific to differentiate HPV + CC from the negative one. Importantly, certain miRNAs render it possible to identify CC metastasis to the lymph nodes.

LncRNAs are ≥200 nt RNAs with very complex secondary structures and a myriad of cellular functions: i) Maintaining the chromatin structure and regulating gene transcription ( 73 ), ii) They are molecular scaffolds for several factors involved in transcription control ( 74 ) and iii) They are miRNAs sponges ( 75 ). These type of RNAs have been detected in body fluids and have been associated with cancer, including CC; however, the information regarding circulating lncRNAs participating in CC is very scarce. Sun et al ( 27 ) found that lncRNAs HOTAIR, PVT1, XLOC_000303 and {"type":"entrez-nucleotide","attrs":{"text":"AL592284","term_id":"16555521","term_text":"AL592284"}} AL592284 are overexpressed in the blood serum of patients with CC when compared with the controls. The analysis of these four lncRNAs together improved the AUC value: 0.875. In a similar way, the analysis of the overexpressed lncRNAs CCAT2, LINC01133 and LINC00511 by including the SCC-A, increased the AUC value to 0.94( 28 ). Meanwhile, the expression of HOTAIR was increased in patients with CC relative to the controls and this correlated with numerous clinical aspects as well as with tumor recurrence and short overall survival ( 76 ). The identification of more circulating lncRNAs as potential CC biomarkers will definitely have a noticeable impact on the diagnosis, prognosis and response to treatments of this type of cancer. In addition, the discovery of the functions performed by these RNAs in time shall allow the identification of therapeutic targets in the future.

4. The estrogen effect on the expression of biomarkers

There is a close relationship between gynecological cancers and alterations in hormone-mediated regulatory pathways, modifying gene expression. Most information is related to protein biomarkers and some of them were regulated by estrogens in tissues: SCC-Ag, C-125, VEGFA and ACTN4, and only circulating HMGB1 and YKL-40 were regulated by estrogens ( 77-81 ). Notably, the circulating miR-21 expression was downregulated by estrogens ( 82 ).

To the best of our knowledge, for the remaining biomarkers there is no evidence indicating changes on their circulating expression in response to estrogens; however, this does not mean that their expression cannot be regulated by this hormone, since most of them show a close relationship with the expression of estrogen receptors.

cDNA was discovered several years ago ( 82 ) and its relationship with cancer was later identified ( 83 ). The total cDNA concentration is considerably lower in healthy individuals than in patients with cancer ( 84 ) and it varies depending on the cancer type ( 85 ). Notably, diverse subtypes of cfDNA can be found in circulation, such as mitochondrial DNA and extrachromosomal and single-stranded DNA, viral, bacterial, and food-derived ( 86 ). The majority of free cDNA is originated from the nucleus and it is packaged in mono- or oligonucleosomes, but most free cDNA is associated with exosomes. Free cDNA release does not correlate with the necrosis and apoptosis levels, but it does correlate with the percentage of cells in G1 phase ( 87 ). Perhaps most importantly, cDNA appears to have various cancer-related functions ( 88-90 ).

Previous studies showed that HPV-cDNA detection positively correlates with low-grade cervical lesions (LGCL) and high-grade cervical lesions (HGCL), CIN and CC, tumor grade, and with the genomic HPV insertion, which is associated with a poor patient's prognosis ( 91-98 ) ( Table III ). Importantly, Rungkamoltip et al ( 29 ) showed a 100% sensitivity and 88% specificity to detect E7 HPV16/18 cfDNA by using the amplification-by recombinase polymerase-in combination with lateral Flow strip. In addition to cDNA, the presence of specific cDNA mutations allows to detect CC from healthy individuals and positively correlates with disease progression and with a shorter progression-free survival, as well as with the overall survival of patients with metastatic relapse CC compared with the controls (patients without any detectable of these mutations) ( 99 ).

cDNA expression levels.

CC, cervical cancer; SCC, squamous cell carcinoma; cDNA, circulating DNA.

Very importantly, cDNA detection allows to differentiate among LGCL and HGCL, and CC from patients with non-HPV dependent CC as well as from individuals without CC. LGCL detection by means of cDNA is very promising since the early detection of this type of lesions can significantly prevent their progression to cancer. In addition, cDNA concentration appears to be useful for monitoring treatment response and patient's prognosis.

6. Putative molecular mechanisms altered by the CC biomarkers

Making a prediction of which mechanisms will be regulated by specific circulating molecules-only based on their canonical functions-is a high-risk task. This is because the few studies that have focused on studying the action of circulating molecules have elucidated mechanisms of action somewhat unexpected and that have nothing to do with the previously reported effects.

In general, it is known that exogenous miRNAs regulate gene expression through the canonical pathway, involving the binding to their target mRNA; however, Fabbri et al ( 100 ) revealed that miRs-21 and -29a function by a different mechanism. The aforementioned study demonstrated the interaction of these miRNAs with Toll-like receptor (TLR) 7 and TRL8 in cells from the immune system. Notably, the binding of miRs-21 and -29a to these receptors triggered a prometastatic inflammatory response, resulting in the tumor growth induction and metastasis. Thus, this is the first indication that miRNAs function as paracrine agonists of TLRs to regulate tumor environment.

Kyoto encyclopedia of genes and genomes (KEGG) analysis

Based on canonical functions reported for the proteins proposed as biomarkers for CC, KEGG analysis showed their involvement mainly in the control of signaling pathways, such as PI3K-Akt, HIF-1, and Rap1, among others ( Table IV ). The cellular processes that may be modified by changes in these signaling pathways were cell proliferation, adhesion, migration, cytoskeleton remodeling and gene expression regulation ( Table IV ).

Kyoto Encyclopedia of Genes and Genomes analysis.

VEGF, vascular endothelial growth factor; ACTN4, Actinin 4; CSF, colony stimulating factor.

DIANA miRPath analysis (Tarbase)

Changes on expression of miRNAs and/or on their function could alter numerous signaling pathways and cellular processes, which is related to their ability to regulate several mRNAs in the same cell. Secretion of miRNAs to blood serum and target organ recognition could mainly alter proteoglycans in cancer, pathways in cancer, renal cell carcinoma, viral carcinogenesis, among others; these signaling pathways control cellular processes related with hallmarks of cancer ( Table V ).

DIANA miRPath v.3.

Numerous functional studies are necessary to know the mechanism(s) of action of each of these molecules separately and/or together, and what ‘benefit’ the tumor obtains by releasing these molecules.

7. Expression of circulating biomarkers in other HPV-related cancers

The aforementioned biomarkers are postulated as a favorable tool for both the detection of cervical lesions and cancer; however, various studies have shown the expression of some of these biomarkers in other types of HPV-related cancers. Their expression has been detected mainly at the tumor level and to a markedly lesser extent as circulating molecules. SCC-A is the most studied biomarker and is overexpressed in distinct squamous cell cancers, including the following: Esophagus, lung, head, neck, and in anal canal, and uterine cervix, as well as in vulvar and penile carcinoma ( 101-105 ). Meanwhile, YKL-40 has demonstrated high tissue levels in anal carcinoma and it has been detected in the plasma of patients with esophageal cancer ( 106 ) and CA-125 showed relatively high circulating levels in vulvar carcinoma ( 107 ). In addition, CA-125 had an increased expression in oropharyngeal cancer ( 108 ) and relatively high VEGFA expression levels were detected in vulvar carcinoma ( 109 ) and oropharyngeal cancer ( 110 ). Although PIGF was detected in oropharyngeal cancer, its expression was not related with the malignancy of this cancer type ( 111 ).

In the case of ncRNAs, to the best of our knowledge only miR-205 and HOTAIR have been related with head and neck ( 112 ), and oropharyngeal cancers ( 113 ), as well as with cervicovaginal lavage specimens, respectively ( 114 ).

8. How feasible is it to use a test of this type in the heath sector of undeveloped countries?

Even though the Mexican Institute of Social Security has a substantial cost for the detection, follow-up and treatment of CC, this cancer type remains the second most common in Mexican women after breast cancer. A previous study carried out by Granados-García et al ( 17 ) revealed the high cost of evaluating a patient's condition regarding CC by cytology, colposcopy, biopsies, and pathology, as well as by diagnostic tests and treatments for cervical intraepithelial neoplasia grade II and III (CIN 2/3) and CC. The aforementioned study identified that the cost to perform 2.7 million cytology tests was nearly 38 million dollars, representing 26.1% of the total program cost (145.4 million). False negatives account for nearly 43% of the program costs. According to the aforementioned results, it was concluded that the low sensitivity of the cytology test generates high rates of false negatives, resulting in high institutional costs from the treatment of undetected CC cases.

In accordance with the aforementioned studies, the establishment of a panel of biomarkers with high sensitivity and specificity would be a great molecular tool to improve the diagnosis and treatment of women with LGCLs, HGCLs and CC. An increase in the detection of women with LGCLs and HGCLs-by this panel-may decrease the number of women progressing towards CC.

9. The best biomarkers panel, according to the authors' point of view

From the authors' point of view, the biomarkers that would have a greater impact on women and health sector are those detecting both LGCLs and HGCLs. Early detection of these type of lesions would allow early treatment of women and this would considerably decrease the progression towards cancer. At this point it is important to mention that the use of this biomarker panel will increase the power of detection, prognosis and response to treatments ( Table VI ).

Panel of biomarkers.

miR, microRNA; CC, cervical cancer.

10. Conclusions and future directions

As observed, early CC detection is a crucial factor to effectively treat low-grade CC lesions and thus avoid the transition to cancer; therefore, the establishment of molecular tools that allow performing this task is imperative. Currently, there are diverse biomolecules-particularly ncRNAs-which have a high sensitivity and specificity to detect LGCLs as well as CC, thus the establishment of these biomarkers for their use in the clinical studies to detect LGCLs and CC is crucial. In addition, the biomolecules that enable us to know the response to treatments is also very important and, in the same way, it should be part of the molecular tools used in the medical attention.

Collectively, the biomarkers found to date have great potential to be used as clinically useful biomarkers for detection and response to treatments. Further studies are needed to establish which are the ones that will best support the medical attention.


Funding statement.

Funding: The present study was supported by Proyectos-ATSO.

Availability of data and materials

Authors' contributions.

RREG searched and organized the information and wrote the manuscript. MGS reviewed the last version of the manuscript. MAVF reviewed and corrected the information of the last version of the manuscript. All authors read and approved the final version of the manuscript.

Ethics approval and consent to participate

Patient consent for publication, competing interests.

The authors declare that they have no competing interests.

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Home > Cancer Research Catalyst > Expanding Global Access to Cervical Cancer Prevention, Screening, and Treatment 

Expanding Global Access to Cervical Cancer Prevention, Screening, and Treatment 

According to the National Cancer Institute , the incidence of cervical cancer in the United States has been steadily declining in recent decades, from an estimated 11.2 cases per 100,000 women in 1992 to 6.7 cases per 100,000 women in 2019. Statistics from other parts of the world, however, paint a substantially different picture. 

Graphic showing that January is Cervical Cancer Awareness Month.

In the United States, the incidence in 2019 is nearing what the World Health Organization (WHO) considers the threshold of near-elimination, defined as 4 cases per 100,000 women. In fact, a 2021 study published in Cancer Epidemiology, Biomarkers & Prevention , a journal of the AACR, showed that some areas of the United States may reach near-elimination by 2030. 

Meanwhile, cervical cancer ranked as the fourth most common cancer worldwide in 2020, causing an estimated 342,000 deaths that year.  

Around 90% of those deaths occurred in low- and middle-income countries (LMICs). 

In 2020, the WHO launched the Cervical Cancer Elimination Initiative , outlining goals that, if met by 2030, could spur global near-elimination of cervical cancer by 2100. The goals include: 

  • vaccinating 90% of girls by age 15; 
  • screening 70% of women for HPV infection by age 35 and again by age 45; and   
  • delivering adequate treatment to 90% of cervical cancer patients. 

These goals rely on trained providers and resources that may be scarce in LMICs. Fortunately, creative solutions engineered by researchers around the world using resource-conscious ways to vaccinate, screen, and treat patients with cervical cancer provide hope that these goals may be attainable. 

Facilitating Self-administered Treatment  

Chemtai Mungo, MD, MPH , an assistant professor of obstetrics and gynecology at the University of North Carolina Lineberger Comprehensive Cancer Center, has seen firsthand the challenges that LMICs face when battling cervical cancer. Having grown up in Kenya and undergone medical training in the United States, she is quite familiar with the differences in cervical cancer management between the two countries. 

“During my training, I almost never took care of a woman with cervical cancer; I never saw women dying from cervical cancer in the United States,” she said in an interview with AACR Stories . “But when I did spend time abroad, there were a lot of women with advanced cases dying.” 

Photo of Chemtai Mungo, MD, MPH

Mungo was honored as a  NextGen Star  at the AACR Annual Meeting 2023 , where she explained some of the reasons underlying the stark disparities.

The low prevalence of obstetrician/gynecologists in Kenya can make it difficult to secure an appointment, and patients sometimes have to travel significant distances to see a specialist. 

Further, infection with the human immunodeficiency virus (HIV) can weaken women’s immune systems, making it harder to fight off the HPV infection that causes most cases of cervical cancer.

An estimated 67% of people living with HIV worldwide reside in sub-Saharan Africa. 

Mungo hypothesized that a cheaper, more accessible treatment method may help reach women with high-risk cervical lesions or HPV infections that won’t go away on their own. She and her colleagues are currently testing the feasibility of a self-administered intravaginal chemotherapy treatment for such patients. 

While studies performed in the United States have demonstrated preliminary efficacy of the method — both for the first-line treatment of patients who could not undergo surgery and to prevent relapse in patients post-surgery — Mungo sought to explore whether the solution might be practical in Kenya. 

Mungo and colleagues have two ongoing studies exploring these issues. One—funded in part by the Victoria’s Secret Global Fund for Women’s Cancers Career Development Award , in partnership with Pelotonia and the AACR—aims to study treatment uptake, adherence to the treatment schedule, and treatment safety in women who are offered self-administered therapy after a surgical excision or ablation procedure. In the other, researchers are performing qualitative interviews with women who receive the self-administered treatment to gain a better understanding of their experience, including their safety, privacy, and ability to negotiate sexual abstinence with their partners during treatment. 

“Cancer is a disease that affects all people, not just those in the United States,” Mungo said. “Equity must not be focused on American cancer patients only, but globally, because innovation internationally will improve the lives of American patients and vice versa.” 

Improving Screening  

Effectively treating patients with cervical cancer or precancer requires the detection of cervical abnormalities, which often do not cause symptoms.

The WHO recommends regular cervical inspection and sampling of cervical tissue, but they also recommend at least two lifetime tests for HPV. 

Collection of cells to test for HPV.

This requires patients to visit a doctor’s office, which can create hurdles to treatment compliance, especially in LMICs. 

Numerous studies have evaluated vaginal self-sampling to detect HPV and found the efficacy to be similar to that of cervical sampling performed in a clinic.

But questions remain regarding how well these tests identified patients with cervical lesions as well as what types of tests worked best. 

A recent prospective study in Cancer Prevention Research , a journal of the AACR, evaluated the detection rates of high-risk (likely to cause cancer) HPV types in vaginal and cervical samples from the same 5,856 patients.

The study confirmed that the identification of high-risk HPV was similar between vaginal and cervical testing; 13.7% of cervical samples and 15.3% of vaginal samples tested positive.  

Among those who tested positive for high-risk HPV, patients who were found to have CIN3—the highest grade of cervical precancer—had received similar results from both sampling modalities, with only one CIN3 case having different vaginal and cervical testing results. 

Since follow-up clinical visits may pose challenges in resource-limited settings, the researchers also evaluated whether they could effectively triage patients who tested positive for high-risk HPV to determine who should be referred for intensive cervical examination. Among self-collected vaginal samples, detection of the two most carcinogenic HPV types—HPV16 and HPV18—appeared to identify precancerous lesions with the best sensitivity and specificity. Testing for the top five HPV types resulted in a similar sensitivity but with a much higher false-positive rate. 

Therefore, the researchers concluded that vaginal self-sampling followed by genotyping for HPV16 and HPV18 may efficiently and accurately identify patients with precancerous lesions who may require treatment and follow-up. In low-resource settings, these measures may reduce the costs and logistical hurdles associated with effective screening. 

Expanding Vaccine Access  

Because HPV causes more than 90% of cervical cancer cases, reducing the spread of HPV can potentially prevent almost all cases of cervical cancer. In the United States, vaccines against HPV first became available in 2006 and are recommended for all adolescents before the onset of sexual activity. 

The U.S. Centers for Disease Control and Prevention (CDC) recommend a two-dose series for children who receive the vaccine between ages 9 and 15 and a three-dose series for individuals aged 15 to 26. The vaccine is offered to both boys and girls because vaccinating boys can help decrease the spread of HPV, and because HPV increases the risk of certain cancers in men, such as anal , penile , and oropharyngeal cancers. 

Guidelines and rates of vaccine uptake may vary, however, in settings where vaccine doses are harder to come by and multiple vaccination appointments may be unrealistic. For that reason, the WHO had long recommended a two-dose series, predominantly for girls. 

But what if one dose can provide similar protection to two? Could that eliminate some of the resource strain and help vaccinate more children? 

A handful of recent trials have tested this approach. In the KEN SHE trial , researchers vaccinated Kenyan girls and women aged 15 to 20 with a single dose of either a bivalent vaccine (targeting HPV16 and HPV18) or a nonavalent vaccine (targeting nine HPV types, including seven associated with cervical cancer).

At 18 months post-vaccination, both vaccines were 97.5% effective at preventing persistent HPV infections. The researchers intend to follow up on these patients at regular intervals to monitor the continued efficacy of the vaccine. 

Similar findings have been reported in trials monitoring patients for 10 years after receiving a single bivalent vaccine dose in Costa Rica or a single quadrivalent (targeting four HPV types) vaccine dose in India. 

Based on these and other studies, in December 2022, the WHO updated their HPV vaccination guidelines to allow for the use of a single vaccine dose for girls aged 9 to 20; individuals older than 20, who have HIV, or who are immunocompromised should still receive at least two doses. 

Officials hope the new guidelines will improve vaccine access by freeing up more doses and eliminating logistical challenges for patients needing to return for a second dose.  

“Averting the development of cervical cancer by increasing access to effective vaccines is a highly significant step in alleviating unnecessary illness and death,” a WHO spokesperson wrote in a news release about the update. 

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