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.

—Tarteskikar

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

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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The Foundation for Women’s Cancer (FWC) steadily pursues its mission of supporting research, education and public awareness of gynecologic cancers.

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May's Story: Finding Joy After Cervical Cancer

May Leahy, pictured during a hospital stay holding a gift given to her by a member of her care team. (Courtesy of May Leahy)

May Leahy was diagnosed with stage 3 cervical cancer in 2018, just a few months shy of her 35th birthday. The tumultuous years that followed were the most difficult she has ever endured. She retells her cancer journey not without shedding a few a tears but makes a point to say, “I’m crying, not because I’m sad. I’m crying tears of joy and gratitude.”

May’s care team at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian / Columbia University Irving Medical Center is led by gynecologic oncologist Caryn St. Clair , MD, who treated the cervical cancer with chemotherapy and radiotherapy. After the cancer recurred in 2019, May went through chemotherapy once again and developed a fistula for which colorectal surgery was involved. A year later, the cancer spread to May’s liver and the lesion was resected and treated with immunotherapy . She also underwent a type of non-surgical radiotherapy called stereotactic body radiotherapy (SBRT), which delivers precise and targeted radiation in fewer high-dose treatments than traditional radiation therapy.

Now more than five years since her diagnosis, May has been off treatment for more than two years, and remains free of disease.

Now five years since her cervical cancer diagnosis, May Leahy has been off treatment for more than two years, and remains free of disease. (Courtesy of May Leahy)

“We all go through trials and tribulations in life. Every human in the world experiences challenges, big or small. Being told I have cancer was the biggest shock of my life,” says May, a Brooklyn native. “I am so grateful to Dr. St. Clair. She moved so quickly with me. She didn’t sit on anything. I always felt like a priority.”

Dr. St. Clair remembers each step along May’s journey, which she says, “has not been an easy one.” Through it all, May has remained strong and determined.

“She has been an inspiration to the many team members involved in her care,” says Dr. St. Clair, assistant professor of obstetrics and gynecology at Columbia’s Vagelos College of Physicians and Surgeons . “I am grateful to all of my colleagues who have helped treat May. She is a great patient and just a lovely human. I couldn’t be happier that she’s done so well after such a long road.”

In December during a routine exam, May was informed that she has now graduated to scheduling follow-up visits every six months rather than every three. To this, she replied with a resounding, “Amazing!”

“I had to tell myself from the very beginning that this isn't a death sentence,” says May. “I know every case is different but if I can share anything from my own experience with someone who has cervical cancer, I’d say that even in the darkest moments, you’ll get through this. Keep your mind strong and tell yourself from the very beginning, ‘I'm going to fight this.’ You’ll fall down many times and you’ll get back up, many times. Keep running through that dark tunnel, and you’ll see the sun at the end. It will come out.”

Related Information

Meet our team, caryn m st. clair, md, cervical cancer.

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 .

Hysterectomy

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

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

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 ClinicalTrials.gov 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 .

National Health Council

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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  • 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

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?
  • Cervical cancer. Cancer.Net. https://www.cancer.net/cancer-types/cervical-cancer/view-all. Accessed March 27, 2023.
  • Gershenson DM, et al. Malignant diseases of the cervix. In: Comprehensive Gynecology. 8th ed. Elsevier; 2022. https://www.clinicalkey.com. 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. https://www.clinicalkey.com. Accessed March 27, 2023.
  • Cervical cancer. National Comprehensive Cancer Network. ps://www.nccn.org/guidelines/guidelines-detail?category=1&id=1426. Accessed March 27, 2023.
  • AskMayoExpert. Cervical cancer screening (adult). Mayo Clinic; 2022.
  • Palliative care. National Comprehensive Cancer Network. https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1454. Accessed March 27, 2023.
  • What is cervical cancer? National Cancer Institute. https://www.cancer.gov/types/cervical. Accessed March 27, 2023.
  • What is cervical cancer? A Mayo Clinic expert explains
  • Where cervical cancer begins

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JENNIFER WIPPERMAN, MD, MPH, TARA NEIL, MD, AND TRACY WILLIAMS, MD

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

Pathogenesis

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

Adenocarcinoma

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. https://www.cdc.gov/reproductivehealth/unintendedpregnancy/pdf/legal_summary-chart_english_final_tag508.pdf . 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. https://seer.cancer.gov/archive/publications/ses/ses_monograph.pdf . 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. https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf [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.

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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 cancer—and 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.

Adenocarcinoma

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.

“Here’s How I Knew I Had Cervical Cancer”: One Survivor’s 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 cervix—being 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 65—yet 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 cancer—rather, 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 smears—having 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:

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

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

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cervical cancer

Cervical cancer, which occurs when cancer cells develop on the surface of the cervix, is a slow-growing cancer that is almost always the result of a sexually transmitted infection called human papillomavirus (HPV). In most cases, HPV clears on its own with the help of the immune system. When it doesn’t clear, however, it can turn into a precancerous condition called dysplasia that can progress into cervical cancer over time.

Pap smear is a test that can detect precancerous cells so they can be treated before they turn cancerous and is often performed by a gynecologist or your primary care provider.

Cervical cancer at UK Markey Cancer Center

Using state-of-the-art technology and leading-edge medical and surgical interventions, Markey’s cervical cancer team provides advanced and timely diagnosis and individualized, ongoing care for patients. Each patient is cared for by a team of specialists who meet regularly to discuss individual patient cases and treatment plans. This multidisciplinary team will work with you and your doctor to coordinate a care plan designed to offer the best outcomes.

Markey has provided state-of-the-art cancer care for more than 30 years, and we are proud to be the only cancer center in Kentucky designated by the National Cancer Institute. Since 2017, Markey Cancer Center has been nationally recognized as a top 50 cancer center by U.S. News & World Report .

  • Survival rates
  • Risk factors
  • Your first visit/what to expect
  • Clinical trials

Cervical cancer can cause a variety of symptoms, including:

  • Abnormal bleeding, including irregular, heavy or longer periods
  • Pain in and around the pelvis, with or without sex
  • Unusual vaginal discharge

When the cancer is more advanced, patients may experience blood in the urine, difficulty while urinating or having a bowel movement or/and unexplained leg swelling.

According to the American Cancer Society , the survival rate for cervical cancer is 92 percent when it is detected before it can spread. When cervical cancer spreads to nearby areas of the body, the survival rate is 58 percent. After cervical cancer spreads throughout the body, the survival rate drops to 17 percent.

You can lower your risk of cancer by taking steps to build a healthy lifestyle. Here are some ways you can lower your risk for this disease, as well as improve your overall basic health:

  • Avoid using tobacco products. Tobacco has been tied to multiple cancers, and it is responsible for 90 percent of lung cancer deaths.
  • Stay physically active. Your physical activity is related to risk for colon and breast cancer. Excess weight gained from inactivity increases the risk of multiple cancers.
  • Limit alcohol consumption. It is important to be mindful of how much alcohol you drink. Alcohol intake, even in moderate amounts, can increase the risk for colon, breast, esophageal and oropharyngeal cancer.
  • Learn about screenings. Your primary care doctor can recommend appropriate cancer screenings based on your age, personal risk and family history.

Women are at highest risk for cervical cancer after age 40, but it can develop at any age. Cervical cancer is usually the result of HPV, and you’re at highest risk for HPV if you:

  • Begin having sex before age 18
  • Have sex with a man who has had multiple partners
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Other cervical cancer risk factors include:

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Clinical trials are research studies aimed at evaluating medical, surgical or behavioral interventions to determine if a new treatment is safe and effective.

At the UK Markey Cancer Center, we are advancing cancer care and research to prevent, detect and treat one patient at a time. As a patient at Markey, you have a team of people looking at your individual case, applying the most recent cancer knowledge to give you the best chance of survival.

Markey has more open clinical trials than any other cancer center in the region, giving you access to some of the most advanced options available. Learn more about ongoing clinical trials for treating cervical cancer .

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What to Know About the HPV Vaccine and Cancer Prevention

New research shows many eligible people are not getting the shots.

A pair of hands wearing blue gloves puts a bandage on the arm of a patient.

By Dani Blum

Nearly 20 years after the first vaccine against human papillomavirus became available, many eligible Americans still are not getting the shot — even though it provides powerful protection against the leading cause of cervical cancer and a strong risk factor for anal cancer.

HPV is the most common sexually transmitted infection in the United States, and while most infections are asymptomatic and clear up on their own within two years, a small number persist and can cause cancer. HPV causes nearly all cases of cervical cancer, and can also lead to penile, anal, oral, vulvar and vaginal cancers .

The HPV vaccine, delivered as two or three doses, can significantly cut the risk of infection. It “is really one of the most effective vaccines we have,” said Dr. Lauri Markowitz, the HPV team lead in the Centers for Disease Control and Prevention’s division of viral diseases. But uptake remains stubbornly low: A report released by the C.D.C. this month showed that in 2022, only 38.6 percent of children ages 9 to 17 had received at least one dose of the HPV vaccine. Other new research suggests that HPV vaccination rates stalled in the wake of the coronavirus pandemic.

A study published this week laid out some of the primary reasons cited by parents in the United States who don’t plan to vaccinate their children against HPV, including safety concerns, a lack of knowledge about the vaccine and a belief that it isn’t necessary.

“We are still facing an uphill battle from what I would call inappropriate messaging or incomplete messaging when the vaccine rolled out about why this is so important,” said Karen Knudsen, chief executive of the American Cancer Society.

How does the vaccine work?

The HPV vaccine fools the body into thinking it has come into contact with the virus, marshaling antibodies in defense. Those antibodies can help clear the virus and prevent infection if someone is later exposed, which can happen through oral, anal and vaginal sex .

The vaccine offers protection from the types most likely to cause cervical and anal cancers and genital warts. Since the vaccine was introduced in 2006, infections with the types of HPV that cause most HPV-related cancers and genital warts have fallen by 88 percent among teen girls and by 81 percent among young adult women, according to the C.D.C.

One reason doctors are so enthusiastic about the vaccine is that it is one of very few tools to combat HPV: Condoms do not entirely prevent transmission, and there is no treatment for the virus itself. Researchers believe HPV is responsible for more than 90 percent of cervical and anal cancers and a majority of vaginal, vulvar, and penile cancers.

Who should get it? And how?

Children can be vaccinated starting at age nine. The C.D.C. recommends the vaccine for all preteens from the age of 11 or 12 and anyone up to age 26. It’s most effective before people are exposed to the virus, and “the assumption is that most people have started having sexual intercourse by age 26,” said Dr. Ban Mishu Allos, an associate professor of medicine at Vanderbilt University Medical Center.

The vaccine may still provide some benefit for people over age 26, and is approved up until age 45. The C.D.C. says that people between the ages of 27 and 45 might get the vaccine after talking to their doctors about their risk for new HPV infections.

You can ask your primary care doctor or local health centers for the vaccine. Most insurance plans fully cover it through age 26. Children and adolescents who are uninsured or underinsured can get the shots for free through the Vaccines for Children program. After age 26, insurance may not fully cover the shot, which can cost hundreds of dollars per dose. Merck, which makes the HPV vaccine Gardasil 9, has a patient assistance program for eligible people.

Why are vaccination rates still low?

Researchers believe much of the hesitation stems from a key misunderstanding: “More people perceive it as a sexually transmitted infection prevention vaccine, as opposed to a cancer prevention vaccine,” said Kalyani Sonawane, an associate professor of public health sciences at the M.U.S.C. Hollings Cancer Center and an author of the new paper on parental attitudes toward HPV vaccination.

Dr. Sonawane’s research has also found that many parents are concerned about side effects. But doctors say many people do not experience side effects, and for those that do, the issues are generally mild and can include arm soreness, nausea, dizziness or, in some cases, fainting.

Doctors urge parents to vaccinate their children before they’re likely to become sexually active, which gives some parents pause, said Dr. Monica Woll Rosen, an obstetrician-gynecologist at the University of Michigan Medical School.

“You’re doing something to prevent them from getting cancer in 30 years,” she said, “and the disconnect might be too large for some people to really wrap their heads around.”

Dani Blum is a health reporter for The Times. More about Dani Blum

The Fight Against Cancer

The human papillomavirus vaccine provides powerful protection against the leading cause of cervical cancer and against a strong risk factor for anal cancer. Here’s what to know about the shot.

A recent study adds to growing evidence that exercise is an important part of preventing prostate cancer , the second most common and second most fatal cancer in the United States for men.

No single food can prevent cancer on its own, but experts say that there are some that may help you build the best defense .

The F.D.A. has proposed banning the use of formaldehyde in chemical hair straighteners , which have been linked to increased cancer risk, particularly among Black women .

In 2023, a panel of experts recommended that all women start getting regular mammograms at age 40 , instead of 50, the previous recommendation.

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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

Patients With Cervical Cancer Survivor Can Thrive With Social Support

“When you have support, you have answers to some of your unknowns and that can provide stability and ease in anxiety and depression, and truly propel you into thriving,” a cervical cancer survivor and advocate tells CURE®.

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.

sexual activity after cervical cancer

Follow-Up Examinations More ‘Tolerable’ With Sexual Activity After Cervical Cancer

Sexual activity and vaginal dilation could make follow-up examinations more “tolerable” and “pain free” for survivors of cervical cancer after radiotherapy.

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.’

Keytruda shows best standard care for cervical cancer

Keytruda Plus Chemoradiotherapy Bests Standard of Care in Advanced Cervical Cancer

Adding Keytruda to EBRT and chemotherapy, followed by brachytherapy, improved progression-free survival in patients with newly diagnosed, previously untreated, high-risk locally advanced cervical cancer.

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.

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patient journey cervical cancer

patient journey cervical cancer

Scientists hit major breakthrough in push for off-the-shelf cancer therapy

patient journey cervical cancer

If you buy through a BGR link, we may earn an affiliate commission, helping support our expert product labs.

Cancer experts estimate at least 13,820 new cases of invasive cervical cancer will be diagnosed in women in the United States alone in 2024. Of that number, experts estimate roughly 4,360 will die from the disease. But those numbers could soon change, as Japanese scientists have made a huge breakthrough in the push for an off-the-shelf cancer therapy that could help treat cervical cancer.

However, one key issue with using this method to create an off-the-shelf cancer therapy is that it just isn’t “clinically feasible in terms of both time and cost,” a press release on the research explains. As a result, the researchers at Juntendo University in Japan started looking for ways to make it more feasible.

metastasis is how cancer spreads

The team sought to address one of the biggest roadblocks with using IPSC-derived rejTs. Because those rejTs are created using standardized iPSCs instead of being derived from the patient’s cells, they are often attractive to the body’s natural killer (NK) cells and its CD8+ T lymphocytes .

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As such, finding a way to make the rejTs less noticeable to the body’s NK cells is important, and the researchers at Juntendo University may have found a way to do just that. To start, the scientists deleted all HLA class I antigens from the cells. Without those antigens, the cells are able to evade the CD8+ T lymphocytes.

With these two modifications, the treatment could have a better chance of making it to the cells that it needs to actually target. During testing, the researchers pulled off very promising results, and with further clinical testing, we could be closer than ever to finally having a way to treat cervical cancer.

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patient journey cervical cancer

Josh Hawkins has been writing for over a decade, covering science, gaming, and tech culture. He also is a top-rated product reviewer with experience in extensively researched product comparisons, headphones, and gaming devices.

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  • Mol Clin Oncol
  • 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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Object name is mco-18-02-02609-g02.jpg

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.

Acknowledgements

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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