All About Cervical Cancer
What is the cervix?
The cervix is the name for the lowest part of the uterus. Only women have a uterus. The uterus is where a baby grows and develops when a woman is pregnant. During pregnancy, the uterus grows a great deal in size. When a woman is not pregnant, the uterus is a small, pear-shaped organ that sits between a woman's rectum and her bladder. The cervix connects the uterus with the birth canal (the vagina). Your healthcare provider can look at your cervix and get a sample of cells (pap testing) during a routine pelvic examination.
What is cervical cancer?
Cervical cancer develops when cells in the cervix begin to grow out of control. These cells can also invade nearby tissues or spread throughout the body. Large collections of cells that grow abnormally are called tumors. Usually, cervical cancer is very slow-growing. However, in certain circumstances, it can grow and spread quickly.
Cancers are characterized by the cells that they originally formed from. The most common type of cervical cancer is called squamous cell carcinoma. It originates from cells that lie on the surface of the cervix known as squamous cells. Squamous cell cervical cancer makes up about 80% of all cervical cancers. The second most common form is adenocarcinoma. It comes from cells that make up glands in the cervix. The percentage of cervical cancers that are adenocarcinomas has risen since the 1970s, but no one knows exactly why. About 3% to 5% of cervical cancers have characteristics of both squamous and adenocarcinomas and are called adenosquamous carcinomas. There are a few other very rare types like small cell and neuroendocrine carcinoma, but they are extremely uncommon.
What causes cervical cancer and am I at risk?
Cervical cancer is much more common in developing nations than it is in developed nations. Cervical cancer is the 2nd most common cause of cancer death in developing nations, with 84% of all cervical cancer cases occurring in Africa, Latin American, and Caribbean underdeveloped areas. It is fairly rare in the United States. Every year, an estimated 13,800 cases of cervical cancer are diagnosed in the United States. There has been a 75% decrease in deaths from cervical cancer in developed nations over the past 50 years. Most of this decrease is attributed to the effective institution of cervical cancer screening programs (HPV testing and/or Pap testing) in developed nations.
One of the most important risk factors for cervical cancer is infection with a virus called HPV (human papillomavirus). It should be stressed that only a very small percentage of women who have HPV will develop cervical cancer. Just because you have HPV doesn't mean you will get cancer. However, almost all cervical cancers have evidence of the HPV virus in them, so HPV infection is a major risk factor for developing it. HPV is a sexually transmitted infection (STI) that is incredibly common in the population. In fact, most college-aged men and women have been exposed to HPV.
HPV is the virus that causes genital warts, but having genital warts doesn't necessarily mean you are going to get cervical cancer. There are different subtypes, or strains, of HPV. Only certain subtypes are likely to cause cervical cancer. Often, infection with HPV causes no symptoms at all, until a woman develops a pre-cancerous lesion of the cervix.
Because having an STI is a risk factor for cervical cancer, any risk factor for developing STIs is also a risk factor for developing cervical cancer. These include:
- Having had multiple male sexual partners.
- Starting to have sexual intercourse at an early age.
- Having had male sexual partners who are considered high risk (they have had many sexual partners and/or began having sexual intercourse at an early age).
- Being diagnosed with any other sexually transmitted diseases (like herpes, gonorrhea, syphilis, or Chlamydia).
HIV infection is another risk factor for cervical cancer, but for a slightly different reason. It appears that any condition that weakens your immune system also increases your risk for developing cervical cancer. Conditions that weaken your immune system include HIV, having had an organ transplant, and Hodgkin lymphoma.
Another important risk factor for developing cervical cancer is smoking. Smokers are at least twice as likely as non-smokers to develop cervical tumors. Finally, women who live in poverty seem to be at an increased likelihood of developing and dying from cervical cancer. This could be related to higher smoking rates, or perhaps because of barriers to getting annual screening exams.
Even someone without any risk factors can get cervical cancer. Timely screening and early detection are our best weapons in reducing the number of new cases of cervical cancer.
How can I prevent cervical cancer?
There are several things women can do to decrease the risk of getting cervical cancer. This includes:
- Have regular screenings: The drastic drop in cervical cancer cases and deaths in the United States has been because of HPV and Pap testing. Screening will be discussed more in the next section.
- Get vaccinated:
- Three vaccines, called Gardasil, Gardasil 9, and Ceravix have been developed. Currently, only Gardasil 9 is available in the US.
- The HPV vaccine is recommended for all individuals aged 12-26. The US FDA has approved the vaccine for use up to age 45, however, not all insurance companies cover the HPV vaccine for individuals over the age of 26.
- These vaccines have been demonstrated to be effective in preventing infection with some strains of HPV if they are given before a person is exposed to HPV. Even if you already have HPV, you can still be vaccinated. The vaccine can protect you from other types of HPV
- In addition to cervical cancer, HPV is also a cause of vulvar, vaginal, penile, and anal cancers and some head & neck cancers. It also causes genital warts and leads to abnormal Pap test results that result in further testing or treatment.
- Don't start smoking, and if you are already a smoker, it is time to quit. Smoking has been shown to decrease the immune system’s ability to clear an HPV infection.
- Women can limit their numbers of sexual partners, and delay the onset of sexual activity to reduce risk, as more partners can increase the likelihood of infection.
- Condom and/or dental dam (barrier method) use may decrease areas that are exposed but cannot prevent exposure entirely.
What screening tests are used for cervical cancer?
Cervical cancer is considered a preventable disease. It usually takes a very long time for pre-cancerous lesions to progress to invasive cancers. Effective screening programs in the United States have led to the drastic decline in the numbers of cervical cancer deaths in the last 50 years. For women who do develop cervical cancer in developed nations, 60% of them either have never been screened or haven't been screened in the last five years. The importance of regular cervical cancer screening cannot be overstated.
The mainstay of cervical cancer screening has been the Pap test. Pap is short for Papanicolaou, the inventor of the test, who published a breakthrough paper in 1941. A Pap test is easily performed in your provider's office. During a pelvic examination, your provider uses a wooden spatula and/or a brush to get samples of cervical cells. These cells are placed on a slide, or in a liquid preservative, and sent to a laboratory where an expert in examining cells under a microscope can look for cancerous changes. Many women find the exam uncomfortable, but rarely painful. Depending on the results of the test, your provider may need to perform further examinations.
Although the Pap test is highly effective, it isn't a perfect test. Sometimes, the test may miss cells that have the potential to become an invasive cancer. The test shouldn't be performed when you are menstruating. And, even if the collection goes perfectly, even the best laboratories can miss abnormal cells. This is why women need to have the tests performed on a regular basis.
Recently, the screening recommendations were changed to focus more on HPV testing. HPV testing can theoretically find the vast majority of women who are at risk for developing cervical cancer by identifying those with high-risk HPV infections. There are over 100 subtypes of HPV and certain types are more likely to lead to cervical cancer. The DNA of cervical cells can be tested to identify the presence of high-risk types of HPV. The HPV DNA test can be used for follow-up testing of women with abnormalities identified on a pap test.
The American Cancer Society recommends the following guidelines for cervical cancer screening:
- All women should begin cervical cancer screening at age 25.
- Women between the ages of 25 and 65 should have:
- Primary HPV testing every 5 years. This test is not yet available at many centers/practices.
- If this test is not available, you should be screened with co-testing, which is a combination of an HPV and Pap test. This should be done every 5 years.
- If HPV testing is not available, then a Pap test alone should be performed every three years.
- Women over age 65 who have had regular cervical screenings that were normal should not be screened for cervical cancer.
- Women who have been diagnosed with cervical pre-cancer should continue to be screened until they meet one of the following criteria over the previous 10 years:
- 2 negative, consecutive HPV tests.
- Or 2 negative, consecutive co-tests.
- Or 3 negative, consecutive pap tests in the last 3-5 years.
- Women who have had their uterus and cervix removed in a hysterectomy and have no history of cervical cancer or pre-cancer should not be screened.
- Women who have had the HPV vaccine should still follow the screening recommendations for their age group.
- While the ACS does not recommend cervical cancer screening every year, women should still see their provider for a well-woman checkup.
Women who are at high risk for cervical cancer may need to be screened more often. Women at high risk might include those with HIV infection, organ transplant, or in-utero exposure to the drug DES. They should talk with their doctor or nurse for specific recommendations.
What are the signs of cervical cancer?
The early stages of cervical cancer usually do not have any symptoms. This is why it is important to have screening Pap tests. As a tumor grows in size, it can produce a variety of symptoms including:
- Abnormal bleeding (including bleeding after sexual intercourse, in between periods, heavier/longer lasting menstrual bleeding, or bleeding after menopause).
- Abnormal vaginal discharge (may be foul-smelling).
- Pelvic or back pain.
- Pain with urination.
- Blood in the stool or urine.
- Pain during sex.
Many of these symptoms are non-specific and can represent a variety of different conditions. If you have any of these symptoms, talk with your healthcare provider.
How is cervical cancer diagnosed?
The most common reason for your provider to pursue the diagnosis of cervical cancer is if you have an abnormal HPV and/or Pap test. Remember these tests are screening tests, not diagnostic. Further testing after an abnormal result is needed.
Pap tests help find pre-cancerous lesions in your cervix. A pre-cancerous lesion means that there are abnormal appearing cells, but they haven't invaded past a tissue barrier in your cervix; thus a pre-cancerous lesion cannot spread or harm you. However, if left untreated, a pre-cancerous lesion can evolve into invasive cancer. Pap tests are reported as no abnormal cells, atypical (abnormal) cells of undetermined significance, low-grade abnormal cells, or high-grade abnormal cells. Depending on your specific case, your provider will decide how to proceed.
- A report of no abnormal cells equates to a negative test, meaning you simply need to have the next screening per the screening guidelines.
- Atypical cells of undetermined significance can be handled in three different ways:
- Repeat HPV/Pap test in 4-6 months,
- Colposcopy: Colposcopy is a procedure done during a pelvic exam with the aid of a colposcope, which is like a microscope. By using acetic acid on the cervix and examining it with a colposcope, your provider can look for abnormal areas of your cervix. Colposcopy is uncomfortable, but not painful, and can be done in your gynecologist's office.
- A biopsy is the only way to know for sure if you have cancer. It allows your provider to get cells that can be examined under a microscope. Once the tissue is removed, a pathologist will examine the specimen. A biopsy can be completed in conjunction with colposcopy.
Your provider will decide how to proceed with the workup of a Pap test showing abnormal cells of undetermined significance, depending on the details of your case. If repeat Pap tests are not normal, then you will be referred for colposcopy. If you test positive for HPV, you will be referred for colposcopy. Generally, most patients with low grade abnormal cells, or high grade abnormal cells will be immediately referred for colposcopy. If you are pregnant, an adolescent, HIV positive, or post-menopausal, your provider may have slightly different recommendations. In some cases, the Pap test will have cells that look abnormal but could have come from higher in your uterus. There is a chance that if this happens, you will need to have your uterine lining sampled. Talk to your provider about your Pap test results, and the next steps after an abnormal Pap.
If you are having symptoms (bleeding/discharge) from cervical cancer, then the tumor can probably be seen during a pelvic exam. Any time your provider can see a cervical tumor on a pelvic exam, it will be biopsied. When abnormal appearing tissue is noticed during a colposcopy, it will be biopsied as well. There are a few different ways to do a biopsy:
- A punch biopsy may be used to remove a small section of the cervix.
- LEEP (loop electrosurgical excision procedure) is another method to do a biopsy where a thin slice of the cervix is removed.
- Conization or cone biopsy may be performed. A cone biopsy removes a thicker section of the cervix and allows the pathologist to see if cancerous cells have invaded through the cervix. The cone biopsy has the added value of sometimes being able to cure a pre-cancerous lesion that is localized to a small area.
Other tests that may be performed as part of a diagnostic workup include blood tests, liver function tests, and HIV testing.
How is cervical cancer staged?
After these tests are performed, a stage is determined to help decide the treatment plan. The stage of cancer, or the extent of disease, is based on information gathered through the various tests done as the diagnosis and workup of the cancer is being performed.
Cancer staging assists the provider in making decisions about treatment and plan of care. Cervical cancer is staged using the FIGO system (International Federation of Gynecologists and Obstetricians) and the TNM system (also called tumor - node - metastasis system). Cervical cancer stages range from I-IV. Generally, the higher the stage, the more serious the cancer. The staging system is very complex and is provided at the end of this article for your reference. Your stage is reported on your pathology report – you may want to ask for a copy of this report for your personal files. The staging system is provided in the appendix for review.
How is cervical cancer treated?
Women who have pre-cancerous lesions on biopsy after colposcopy have a few different options with how to proceed. You may decide on a specific option depending on whether or not you plan to have children in the future, your current health status and life expectancy, and your concerns about the future and the possibility of having cancer come back. You should talk to your provider about your fears, concerns and preferences.
If you have low-grade lesions, you may choose to not have any further treatment, especially if the biopsy removed the entire lesion. If you decide to do this, you will need more frequent pelvic exams and Pap tests. Talk with your healthcare provider about how often you will need to have these exams.
There are several ways to remove pre-cancerous lesions without removing the entire uterus (and thus preserving your ability to have a baby in the future). Options include:
- Cryosurgery (freezing off the abnormal lesion).
- LEEP (the same type of electrosurgical procedure used for biopsies).
- Conization (the thicker type of biopsy that gets tissue under the surface).
- Laser cell removal.
Women who do not have any plans to have children in the future and are particularly worried about their chances of getting invasive cancer may elect to have a hysterectomy (a surgery that removes your uterus and cervix). This procedure is more invasive than any of the previously mentioned treatment modalities but can provide peace of mind to women who do not want to have children.
Surgery is generally used in early-stage cervical cancers. The goal of surgery is to remove as much disease as possible. However, it usually isn't used unless all of the cancer can be removed at the time of surgery. Cancers that have a high chance of already spreading to the lymph nodes are not treated with surgery (lymph nodes are small, pea-sized pieces of tissue that filter and clean lymph, a liquid waste product).
There are a few different types of surgeries that can be performed. The type of surgery depends on the stage of the tumor. Surgical procedures for cervical cancer include:
- Trachelectomy- Removal of the cervix, upper vagina, and tissue surrounding the cervix. Pelvic lymph nodes may also be removed.
- Hysterectomy- Removal of the uterus and cervix. Pelvic lymph nodes may also be removed. Depending on the amount of disease, your provider may have to remove tissues around the uterus, as well as part of the vagina and the fallopian tubes.
One of the benefits of surgery in young women is that sometimes their ovaries can be left. This keeps them from going through menopause at an early age. Higher stage disease is usually treated with radiation and chemotherapy, but sometimes surgery is used if cervical cancer comes back after it has already been treated.
A pelvic exenteration is reserved for recurrent cervical cancers. A pelvic exenteration is a major surgery in which the uterus, cervix, fallopian tubes, ovaries, vagina, bladder, rectum, and part of the colon are removed.
Radiation therapy has been shown to be very effective in treating cervical cancer. Radiation therapy uses high energy x-rays to kill cancer cells. Radiation therapy is another option besides surgery for early-stage cervical cancer. Surgery and radiation have been shown to be equivalent treatments for early-stage cervical cancers. Advanced stage cervical cancer is also treated with radiation. Radiation also helps to avoid surgery in patients who are too ill to risk having anesthesia. Radiation has the benefit of being able to treat all of the disease in the radiation field, so that lymph nodes can be treated as well as the primary tumor in the course of the same treatment.
Radiation therapy for cervical cancer either comes from an external source (outside of the patient, known as external beam radiation) or an internal source (inside the patient, known as brachytherapy). The duration of your treatment will be determined by your treatment team. The treatment takes just a few minutes and is painless.
The type of radiation therapy used depends on the stage of your tumor. In all cervical cancers above stage IB, the standard approach with radiation therapy is to use external beam radiation coupled with internal brachytherapy. Brachytherapy (also called intracavitary irradiation) allows your radiation oncologist to "boost" the radiation dose to the tumor site. This provides an added impact to the tumor while sparing your normal tissues. This is done by inserting a hollow, metal tube with two egg-shaped cartridges into your vagina. Then, a small radioactive source is placed in the tube and cartridges. A computer has calculated how long the source needs to be there, but usually, for what is called low dose rate (LDR) brachytherapy, you will need to have the source in for a few days. This procedure is done in the hospital because for those few days you have to stay in bed.
Another type of brachytherapy, called high dose rate (HDR) brachytherapy, uses more powerful sources that only stay in for a few minutes. Although this option usually sounds more appealing to patients, there is debate as to which type is more effective and some institutions favor one over the other. Talk to your care provider about your options and their opinions as to HDR versus LDR for cervical cancer treatment.
Another use of radiation is in palliative care. In patients with very advanced cases of cervical cancer, the goal of treatment is to ease pain or symptoms, rather than trying to cure their disease.
In any setting, radiation is often combined with chemotherapy, and, depending on your case, your provider will decide with you on the best possible treatment arrangement for your lifestyle and wishes.
Despite the fact that tumors are removed by surgery or treated with radiation, there is always a risk of recurrence because there may be microscopic cancer cells left in the body. In order to decrease the risk of a recurrence (the cancer coming back), you may be offered chemotherapy.
Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. Most patients in good medical condition and receiving radiation for stage IIA or higher cervical cancer will be offered chemotherapy in addition to their radiation. It may even be offered for earlier stage cases depending on the patient and her disease. There have been many studies that demonstrate the usefulness of adding chemotherapy to radiation in terms of decreasing mortality from cervical cancer.
There are many different chemotherapy drugs, and they are often given in combinations for a series of months. Depending on the type of chemotherapy regimen you receive, you may get medication every week or every few weeks. The most commonly used regimens (combinations) use a drug called cisplatin combined with another medication, typically etoposide, paclitaxel, topotecan, carboplatin and/or bevacizumab. Pembrolizumab, albumin-bound paclitaxel, docetaxel, fluorouracil, gemcitabine, ifosfamide, irinotecan, mitomycin, pemetrexed, and vinorelbine may be used as second-line therapy after recurrence. In some cases where the tumor has certain genetic mutations, larotrectinib or entrectinib may be used. Your tumor will be tested for these mutations.
There are advantages and disadvantages to each of the different regimens that your health care provider will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your providers to come up with the best regimen for your lifestyle.
There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.
Follow-up Care and Survivorship
Once you have been treated for cervical cancer, you need to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The longer you are free of disease, the less often you will have to go for checkups. Your provider will tell you when they want follow-up visits, Pap tests, and/ or scans depending on your case. Your provider will also do pelvic exams regularly during your office visits. It is very important that you let your provider know about any symptoms you are experiencing and that you keep all of your follow-up appointments.
Fear of recurrence, relationships and sexual health, the financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by cervical cancer survivors. Your healthcare team can identify resources for support and management of these challenges faced during and after cancer.
Cancer survivorship is a relatively new focus of oncology care. With nearly 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.
Resources for More Information
National Cervical Cancer Coalition
Provides education about HPV and cervical cancer, support through a "pals" program that links a woman with another woman who has a similar diagnosis.
Foundation for Women’s Cancers
The Foundation offers comprehensive information by cancer type that can help guide you through your diagnosis and treatment. They also offer the ‘Sisterhood of Survivorship’ to connect with others facing similar challenges.
Hope for Two
Dedicated to providing women diagnosed with cancer while pregnant with information, support, and hope.
Appendix: FIGO Surgical Staging of Cervical Cancer (2018)
Cervical carcinoma confined to the cervix (extension to corpus should be disregarded)
Invasive carcinoma diagnosed only by microscopy. Stromal invasion with a maximum depth of ≤5.0mm
Measured stromal invasion of ≤3.0mm or less in-depth
Measured stromal invasion >3.0mm and ≤5.0mm
Invasive carcinoma with measured deepest invasion >5 mm (greater than stage IA); lesion limited to the cervix uteri with size measured by maximum tumor diameter.
Invasive carcinoma >5mm depth of stromal invasion and ≤2cm in greatest dimension
Invasive carcinoma >2cm and ≤ 4cm in greatest dimension
Invasive carcinoma >4cm in greatest dimension
Cervical carcinoma invading beyond the uterus but not extended onto the lower third of the vagina or to the pelvic wall
Involvement limited to the upper two-thirds of the vagina without parametrial invasion.
Invasive carcinoma ≤4cm in greatest dimension
Invasive carcinoma >4cm in greatest dimension
Parametrial invasion but not up to the pelvic wall
The carcinoma involves the lower third of the vagina and/or extends to the pelvic wall and/or causes hydronephrosis or non-functioning kidney and/or involves pelvic and/or paraaortic lymph nodes
Tumor involving the lower third of the vagina but no extension to the pelvic wall
Carcinoma involves the lower third of the vagina, with no extension to the pelvic wall
Involvement of pelvic and/or paraaortic lymph nodes (including micrometastases), irrespective of tumor size and extent (with r and p notations).
Pelvic lymph node metastasis only
Paraaortic lymph node metastasis only
The carcinoma has extended beyond the true pelvis or has involved (biopsy-proven) the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to stage IV
Spread of the growth to adjacent organs
Spread to distant organs
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