Cervical Cancer

Overview

Unlike breast cancer, cervical cancer may not be a female disease you hear about every day. However, both cervical cancer and the virus that causes most cases of cervical cancer—HPV—are prevalent and worth every woman's attention.

Cancer of the cervix is the fourth most common type of cancer found in women worldwide, after breast, lung and colon cancer. In the United States and other developed countries, cervical cancer rates are much lower; in fact, 85 percent of all cases of cervical cancer occur in developing countries.

The American Cancer Society (ACS) estimates there will be about 13,170 cases of invasive cervical cancer in the United States in 2019, and about 4,250 women will die from the disease.

Cervical cancer is a disease in which cancer cells develop in the tissues of the cervix. The cervix, the lower part of the uterus that protrudes into the vagina, connects the body of the uterus to the vagina. Nearly all cases of cervical cancer can be linked to the human papillomavirus (HPV), a sexually transmitted virus.

There are more than 150 types of HPV, and about 40 high-risk types are linked to cervical cancer. Most women who develop cervical cancer have HPV, but only a small number of women infected with HPV develop cervical cancer. Only persistent HPV infections lead to cervical cancer. Additionally, some low-risk types of HPV cause vaginal and vulvar warts. Other HPV strains cause the warts that sometimes develop on the hands or feet.

The normal cervix is a firm muscle that feels much like the tip of your nose, soft but firm. It is reddish pink, and the outside is covered with normal skin cells called squamous cells. Different cells called columnar (or glandular) cells line the cervical canal. Transformation zones (T-zones) are areas in the body where two cell types meet, and one changes to becomes the other. There is a transformation zone at the cervix, the anal canal and on the tonsils. The line where the two cell types meet—called the squamocolumnar junction (SCJ) is part of the T-zone, and the normal change process of one cell type to another creates metaplastic cells. These changing metaplastic cells are at greatest risk and where abnormal cells most commonly develop when high-risk types of HPV persist in them. Through the female lifespan, the SCJ moves further toward the canal of the cervix and eventually up in the canal. In young women, the T-zone is more exposed on the outside of the cervix (teens through 20s), which makes them more susceptible to cervical infections.

To screen for cervical cancer, health care professionals use the Pap and HPV tests. The Pap test looks for abnormal cell changes that may be mild, moderate or severe precancer or cancer. Screening is meant to find precancer cells and treat them before they progress to invasive cancer. Screening is important because the goal is to find precancer and treat it before cancer has occurred. Additionally, if cancer is present, the earlier health care professionals diagnose it, the better the chance for a cure.

The ACS reports that both incidence of and deaths from cervical cancer have declined markedly over the last several decades. This is no doubt due to more frequent detection and treatment of precancerous and cancerous lesions of the cervix from increased Pap test screening.

Because persistent infection with high-risk strains of HPV can lead to cervical cancer, many medical professionals now also test for the HPV virus in addition to using the Pap test. The U.S. Food and Drug Administration (FDA) has approved use of an HPV test for screening women ages 30 and older and, when combined with a Pap test in women of this age group, the HPV test is better at identifying women at risk for developing cervical cancer than the Pap test alone.

Because the FDA has approved some HPV tests for primary HPV testing in women aged 25 and older, your health care professional may not order a Pap test initially. This is because large amounts of data find that the HPV test can identify women who may have disease that was missed by the Pap as well as identify women who have future risk as long as the high-risk type of HPV persists.

The FDA has also approved an HPV vaccine called Gardasil 9 to protect women against nine strains of HPV. These include the two most common high-risk (cancer-causing) types of HPV, strains 16 and 18, and the two most common low-risk types of HPV, 6 and 11, which cause 90 percent of genital warts. It also protects against five other high-risk types: 31, 33, 45, 52 and 58. Together these types cause most cases of cervical cancer, as well as many cancers of the vulva, vagina, anus, penis and throat.

Ideally, girls and boys should receive the HPV vaccine before they become infected with HPV (in other words, before they become sexually active). As such, the vaccine is approved for children as young as nine and is routinely recommended as a series of shots for girls and boys at age 11 or 12.

Health care professionals also recommend the vaccine for females ages 13 to 26 and males ages 13 to 21 who did not receive the vaccine when they were younger. The FDA has approved Gardasil 9 for women and men up to age 45, although health care professional usually don't give it after age 26, because it is unlikely to provide much benefit to older people. This is a decision to be made by the individual and their health care professional.

If someone is already infected with one of the HPV types in the vaccine, the vaccine will not work against that particular HPV type. It will still work against the remaining types. The vaccine creates antibodies to the HPV types in the vaccine. It does not treat existing infection.

Clinical trials have shown that the HPV vaccine is safe and close to 100 percent effective in preventing HPV strains 16 and 18, which cause 70 percent of cervical cancers. It is also 99 percent effective in preventing HPV strains 6 and 11, which cause about 90 percent of genital warts. The vaccine may come in two or three injections, depending on the age of the person being vaccinated, with patients under 15 years old requiring just two doses and over 15 years old needing three.

The HPV vaccine does not protect against all cancer-causing strains of the HPV virus, so the FDA recommends continued screening with regular Pap and HPV tests appropriate to age, according to published guidelines.

The reason screening is so important for preventing cervical cancer is because the disease usually causes no symptoms in its earliest stages. The detection and treatment of high-grade, severe lesions can prevent progression to invasive cancer. Irregular bleeding, bleeding or pain during sex or vaginal discharge may be symptoms of more advanced disease. If you experience any of these symptoms, you should discuss them with a health care professional.

All women are at risk for cervical cancer, but several factors can increase risk, according to the ACS:

• Persistent infection with high-risk strains of HPV. Most women and men who have been sexually active have been exposed to the HPV virus, which spreads through skin-to-skin contact with an HPV-infected area. However, certain types of sexual behavior increase a woman's risk of getting an HPV infection, such as having sex at an early age, having many sexual partners and having unprotected sex.
  
  Condoms do not completely protect against HPV because the virus spreads via skin-to-skin contact, including the skin in the genital area that may not be covered by a condom. Correct and consistent condom use is still important, however, to protect against AIDS and other sexually transmitted diseases.
• A compromised immune system related to certain illnesses such as human immunodeficiency virus (HIV) infection. Women who are HIV positive are less able to clear HPV or fight cancers like cervical cancer.
• Smoking cigarettes, which exposes the body to cancer-causing chemicals. Women who smoke are about twice as likely to develop cervical cancer. The chemicals produced by tobacco smoke may damage the DNA in cervical cells and make cancer more likely to grow there.
• Infection with chlamydia bacteria, which spreads via sexual contact and may or may not cause symptoms. Researchers don't know exactly why chlamydia infection increases cervical cancer risk, but they think it might be because active immune system cells at the site of a chlamydia infection might damage normal cells and cause them to turn cancerous.
• A diet low in fruits and vegetables. Women who don't eat many fruits and vegetables miss out on protective antioxidants and phytochemicals such as vitamins A, C, E and beta-carotene, all of which have been shown to help prevent cervical cancer and other forms of cancer. Overweight women are also more likely to develop cervical cancer.
• A family history of cervical cancer. If your mother or sister had cervical cancer, you may have a genetic tendency for the disease. This could be because some women are genetically less able to fight off HPV infection than other women.
• Exposure in utero to diethylstilbestrol (DES), a synthetic hormone that was prescribed to pregnant women between 1940 and 1971 to prevent miscarriages. For every 1,000 women whose mothers took DES when they were pregnant, about one develops clear-cell adenocarcinoma (cancer) of the vagina or cervix. For more information on DES exposure, contact the U.S. Centers for Disease Control and Prevention, toll-free: 1-800-CDC-INFO (232-4636), or online at www.cdc.gov.
• Long-term oral contraceptive use (five or more years) may very slightly increase a woman's risk of cancer of the cervix, according to some statistical evidence. However, this risk appears to go back to normal after a woman has been off birth control pills for 10 years. The ACS advises women to discuss the benefits of birth control pills versus this very slight potential risk with their health care professionals.

The death rate from cervical cancer in African-American women is nearly double that of the death rate in Caucasian women. Additionally, Hispanic women develop this cancer nearly twice as often as non-Hispanic Caucasian women. Lack of access to health services (and therefore, less screening), cultural influences and diagnosis of cancer at more advanced stages are all possible reasons for these differences.

Women of all ages are at risk of cervical cancer, but it occurs most often in women 30 and over because they are more likely to have persistent HPV infections. Regardless, it is important that even postmenopausal women continue having regular Pap tests if they still have a cervix. If a woman no longer has a cervix due to a hysterectomy to remove cervical cancer or precancer, she should continue screening with Pap tests and HPV tests. If her cervix was removed during a hysterectomy and there were no signs of cancer and no suspicious Pap tests before the surgery, then she does not need to continue screening. Women over age 65 should stop getting Pap tests if they have had adequate prior screenings: three Pap tests or two Pap tests and one for HPV resulting in negative and no abnormal results in the previous decade.

Discuss your individual screening needs with your health care professional. The guidelines for screening are for the general population. Women who are at risk due to being HIV positive, have history of DES exposure or are immunocompromised are not managed according to the general population guidelines.

The benefits of the Pap test are clear: Because of early detection and treatment of cell changes, over the last 40 years, the death rate for cervical cancer has decreased by more than 50 percent.

Although both the incidence and death rates of cervical cancer are going down, it is still a fairly common cancer in U.S. women, which may be related to the prevalence of infection with HPV. According to the CDC, approximately 79 million people are currently infected with HPV, and up to 14 million new infections occur each year.

Screening and Diagnosis

The Pap and HPV tests are used to screen for cervical cancer. During both tests, an HCP removes cells from the surface of the cervix during a pelvic exam and sends them to a laboratory to be examined. In a Pap test, the lab looks for any cell changes, which can range from mild to moderate or severe precancer or cancer.

The HPV test looks for the virus itself. The test may be used alone or in combination with a Pap test, and the HPV test is better at identifying women at risk for developing cervical cancer than the Pap test alone.

Although uncomfortable, both tests are usually quick and painless.

Screening Guidelines for Cervical Cancer

For many years, ACS, the U.S. Preventive Services Task Force (USPSTF) and the American College of Obstetricians and Gynecologists (ACOG) generally agreed on guidelines for early detection and prevention of cervical cancer. More recently, ACS and USPSTF updated and made changes to their guidelines. Women should speak to their HCP about screening options. The most important thing is to get screened regularly, no matter which test you get.

The recommendations are summarized below:

• Ages 21-24: Pap test every three years. Note: The ACS does not recommend screening until age 25.
• Ages 25-65: There are three options:

• Pap test every three years
• HPV test every five years
• HPV and Pap test together (co-testing) every five years

Women ages 65 and older do not need screening if their prior tests were normal and they're not at high risk for cervical cancer.

Screening Test Results

An abnormal Pap test result doesn't necessarily mean you have cervical cancer. It indicates there are cell changes in the cervix that if left untreated, may lead to cervical cancer.

While the Pap test cannot confirm an HPV infection, it can show cell changes caused by an infection with HPV.

Pap test classifications include:

• Normal — no signs of precancerous changes, cancer or other significant abnormalities
• Unclear (AS-CUS) — cell changes that look abnormal, but it's inconclusive whether they're a result of HPV or other causes such as hormonal changes or an infection; an HPV test is often performed as a follow-up
• Abnormal — cell changes caused by HPV but are not necessarily cancer; further testing is necessary

Like an abnormal Pap test, a positive HPV test does not mean you have cervical cancer. It means that you have the virus that can lead to cervical cancer. A positive test may mean follow-up tests, such as a colposcopy to view the cervix in a greater detail, or a "watch and wait" approach.

To help improve the reliability of your screening, schedule your appointment two weeks after your last period and refrain from having sex, douching, or using tampons, vaginal creams, suppositories, medicines, sprays or powders within 48 hours of the test.

Treatment

Treatment is determined based on location of abnormal cells, colposcopy results, plans for future children and the stage of disease, which can range from stage 0 (also called carcinoma in situ) to stage 4, where the cancer has spread (metastasized) to other parts of the body.

There are several treatment approaches available, and they can be used alone or in various combinations.

Surgery

Surgery is an option for removing both precancer cells and cancer. Procedures to treat precancer include:

• Ablation— the use of cold temperatures or a laser to destroy precancer cells. This may include cryosurgery or laser ablation.
• Conization — the surgical removal of a cone-shaped portion of the cervix. This can be both a diagnostic tool and a treatment. There are three types of conization:

• LEEP — uses a thin wire heated by electricity
• Cold knife — uses a surgical blade
• Laser conization — uses a laser

Procedures to treat invasive cervical cancer:

• Hysterectomy — There are several different types of hysterectomy, but they all involve the removal of the uterus and cervix.

• Simple hysterectomy — removes the uterus and cervix but leaves the ovaries in place. This can be performed vaginally, abdominally, laparoscopically (using a tiny camera placed inside the abdomen through small incisions) or with a robot-assisted laparoscopy
• Radical hysterectomy — removes the uterus and cervix as well as surrounding tissues and is performed through a large incision in the abdomen.

• Trachelectomy — removes the cervix and upper part of the vagina but leaves the uterus intact. This allows women a chance to carry a pregnancy to full-term.
• Pelvic exenteration — used in cases of recurrent cervical cancer, this procedure removes the uterus, cervix, surrounding tissues, lymph nodes and any areas the cancer may have spread to, which can include the bladder, rectum, vagina or part of the colon.

Radiation Therapy

Radiation therapy uses radiation to kill cancer cells. This can be used as the primary treatment or in combination with other treatments. The types of radiation therapy are:

• External beam radiation — This approach is similar to an X-ray, but with much stronger doses of radiation involved. The radiation comes from a machine outside of the body. This method is often combined with chemotherapy.
• Brachytherapy (internal radiation therapy) — Brachytherapy puts the radiation source close to or actually in the cancer with a device that is placed in the vagina or cervix, giving the radiation a short distance to travel. There is both low-dose and high-dose brachytherapy. Low-dose brachytherapy is an in-patient procedure that is administered over the course of a few days. High-dose brachytherapy is an outpatient treatment, administered over several treatments that are usually spread a week or more apart.

Chemotherapy

Chemotherapy is a treatment that uses cancer-fighting medications that fight cancer. They can be administered intravenously (IV) or by mouth and are often given in cycles. Because the medication enters the bloodstream, it can kill cancer in most parts of the body. Radiation treatment and chemotherapy are often used together, as chemotherapy can improve the effectiveness of radiation treatment.

Targeted Therapy

Bevacizumab is a drug that stops tumors from being able to form new blood vessels that provide nutrients to the tumor. By blocking these nutrients, the drug inhibits the growth of the tumor. Bevacizumab may be used along with chemotherapy.

Immunotherapy

Immunotherapy uses a person's natural immune system to fight disease by stimulating the immune system to allow it to efficiently fight cancer cells. Pembrolizumab is a type of immunotherapy that has been shown to be effective in fighting certain types of cervical cancer that recur after chemotherapy or have metastasized (spread to other parts of the body).

Prevention

Most women who develop invasive cervical cancer have not had regular cervical cancer screening. Getting regular screening tests to look for the presence of HPV and identify precancerous changes early, along with HPV vaccination, can prevent cervical cancer.

Reducing or eliminating risk factors can also help prevent cervical cancer:

• Limit exposure to HPV. HPV is very common, so if you're sexually active, there's a good chance you'll be exposed at some point. However, having fewer sexual partners and choosing partners who have had fewer sexual partners can help decrease your chances of exposure.
• Use condoms to protect yourself from sexually transmitted diseases. Note: While condom use will decrease the risk of HPV infection, it can't prevent it entirely.
• Don't smoke cigarettes.

Questions to Ask

The following questions will help guide you to having a useful discussion about cervical cancer with your HCP.

1. What should I do before getting a Pap or HPV test to make sure the test is as accurate as possible?
2. How will I be informed of my test results?
3. If I have abnormal cells on a Pap test or a positive HPV test, what are the next steps?
4. I was diagnosed with HPV. How often do I need follow-up exams?
5. I'm afraid to find out I may have cancer, so I'm afraid to have a pelvic exam, Pap test, or HPV test. What should I do?
6. What is a colposcopy and why do you recommend it? Will it hurt?
7. Can cervical cancer be cured? Can it come back after it's been treated?
8. What experience do you have treating cervical cancer? Have you had specialty training in gynecological oncology?
9. Will I have to be checked for cancer for the rest of my life?
10. What are the risks that my daughter will get cervical cancer, too?

Organizations and Support

For information and support on coping with Cervical Cancer, please see the recommended organizations, books and Spanish-language resources listed below.

American Cancer Society (ACS)
Website: https://www.cancer.org
Address: 250 Williams Street
Atlanta, GA 30303
Hotline: 1-800-ACS-2345 (1-800-227-2345)
Phone: 404-315-1123

American Institute for Cancer Research
Website: https://www.aicr.org
Address: 1759 R Street, NW
Washington, DC 20009
Hotline: 1-800-843-8114
Phone: 202-328-7744
Email: aicrweb@aicr.org

Association of Cancer Online Resources, Inc.
Website: https://www.acor.org
Address: 173 Duane Street, Suite 3A
New York, NY 10013
Phone: 212-226-5525

Cancer Care, Inc.
Website: https://www.cancercare.org
Address: 275 Seventh Ave., Floor 22
New York, NY 10001
Hotline: 1-800-813-HOPE (1-800-813-4673)
Phone: 212-712-8400
Email: info@cancercare.org

Cancer Information and Counseling Line (CICL)
Address: AMC Cancer Research Center
1600 Pierce Street
Denver, CO 80214
Hotline: 1-800-525-3777
Email: contactus@amc.org

Corporate Angel Network
Website: https://www.corpangelnetwork.org
Address: Westchester County Airport
One Loop Road
White Plains, NY 10604
Hotline: 1-866-328-1313
Phone: 914-328-1313
Email: info@corpangelnetwork.org

Foundation for Women's Cancer
Website: https://www.foundationforwomenscancer.org
Address: 230 W. Monroe, Suite 710
Chicago, IL 60606
Phone: 312-578-1439
Email: FWCinfo@sgo.org

Gathering Place
Website: https://www.touchedbycancer.org
Address: The Arnold & Sydell Miller Family Campus 23300 Commerce Park
Beachwood, OH 44122
Phone: 216-595-9546
Email: info@touchedbycancer.org

Mautner Project - The National Lesbian Health Organization
Website: https://www.mautnerproject.org
Address: 1875 Connecticut Ave., NW Suite 710
Washington, DC 20009
Hotline: 1-866-MAUTNER (1-866-628-8637)
Phone: 202-332-5536
Email: info@mautnerproject.org

Memorial Sloan-Kettering Cancer Center, New York
Website: https://www.mskcc.org
Address: 1275 York Ave
New York, NY 10065
Phone: 212-639-2000
Email: publicaffairs@mskcc.org

National Cancer Institute (NCI)
Website: https://www.nci.nih.gov
Address: NCI Public Inquiries Office
6116 Executive Boulevard, Room 3036A
Bethesda, MD 20892
Hotline: 1-800-4-CANCER (1-800-422-6237)
Phone: TTY: 1-800-332-8615

National Cervical Cancer Coalition (NCCC)
Website: https://www.nccc-online.org
Address: 6520 Platt Ave., #693
West Hills, CA 91307
Hotline: 1-800-685-5531
Phone: 818-909-3849
Email: info@nccc-online.org

National Coalition for Cancer Survivorship (NCCS)
Website: https://www.canceradvocacy.org
Address: 1010 Wayne Ave., Suite 770
Silver Spring, MD 20910
Hotline: 1-877-NCCS-YES (1-877-622-7937)
Phone: 301-650-9127
Email: info@canceradvocacy.org

National Comprehensive Cancer Network
Website: https://www.nccn.org
Address: 275 Commerce Dr, Suite 300
Fort Washington, PA 19034
Phone: 215-690-0300

Native American Cancer Research
Website: https://www.natamcancer.org
Address: 3022 South Nova Rd.
Pine, CO 80470-7830
Phone: 303-838-9359
Email: info@natamcancer.net

Prevent Cancer Foundation
Website: https://www.preventcancer.org
Address: 1600 Duke Street, Suite 500
Alexandria, VA 22314
Hotline: 1-800-227-2732
Phone: 703-836-4412

Women's Cancer Resource Center
Website: https://www.wcrc.org
Address: 5741 Telegraph Avenue
Oakland, CA 94609
Hotline: 1-888-421-7900
Phone: 510-420-7900
Email: info@wcrc.org

Books

Johns Hopkins Patients' Guide to Cervical Cancer
by Colleen McCormick, Robert Giuntoli

A Gynecologist's Second Opinion: The Questions & Answers You Need to Take Charge of Your Health
by William H. Parker, Rachel L. Parker

Intimacy After Cancer: A Woman's Guide
by Dr. Sally Kydd, Dana Rowett

The HPV Vaccine Controversy: Sex, Cancer, God, and Politics: A Guide for Parents, Women, Men, and Teenagers
by Shobha S. Krishnan

Spanish-language resources

National Cancer Institute
Website: https://cancernet.nci.nih.gov/sp_menu.htm
Hotline: 1-800-422-6237
Email: nciespanol@mail.nih.gov

H. Lee Moffitt Cancer Center & Research Institute
Website: https://moffitt.org/cancers/cervical-cancer/?lang=sp
Address: 12902 Magnolia Drive
Tampa, FL 33612
Hotline: 1-888-663-3488
Phone: 813-745-4673

Medline Plus: Cervical Cancer
Website: https://www.nlm.nih.gov/medlineplus/spanish/cervicalcancer.html
Address: Customer Service
US National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
Email: custserv@nlm.nih.gov