Cervical cancer screening

Author
Brenda E Sirovich, MD, MS Section Editor
Suzanne W Fletcher, MD
Barbara Goff, MD Deputy Editor
Leah K Moynihan, RNC, MSN
H Nancy Sokol, MD

CERVICAL CANCER SCREENING OVERVIEW — The Pap smear is a common test used to screen women for cervical precancer or cancer. However, most abnormal Pap smears are not due to cancer, but rather caused by infection or low estrogen levels.

This topic reviews the anatomy of the cervix, factors that increase a woman’s risk of having cervical precancer or cancer, tests to detect cervical abnormalities, and a description of both normal and abnormal Pap smear results.

The evaluation and treatment of abnormal Pap smears are discussed separately. (See “Patient information: Management of atypical squamous cells (ASC-US and ASC-H) and low grade cervical squamous intraepithelial lesions (LSIL)” and see “Patient information: Management of high grade cervical squamous intraepithelial lesions (HSIL) and glandular abnormalities (AGC)” and see “Patient information: Treatment of abnormal Pap smears”).

ANATOMY OF THE CERVIX — The cervix is located at the lower end of the uterus (show figure 1). The surface of the cervix includes several layers of cells. Squamous cells make up the outer layer of the cervix and vagina.

The cervix also includes glandular (also called columnar) cells, which line the opening in the cervix. The region where the two cell types meet is called the “transformation” zone (show picture 1). The transformation zone is the region most likely to contain abnormal cells.

CERVICAL CANCER SCREENING TESTS — There are several ways to screen for cervical cancer. The traditional screening test is called a Pap smear. However, other methods, including liquid based cytology and HPV testing, are also available.

Test options

Pap smear — The Pap smear (named after Dr. Papanicolaou) is a method of examining cells from the cervix (show figure 1). The test is not painful, although some women find the procedure uncomfortable.

Liquid based cytology — Liquid-based tests (eg, ThinPrep, SurePath) were developed in the hope of improving the accuracy of the Pap smear. However, studies that have compared the traditional Pap smear to liquid based cytology do not prove one test to be more accurate than another.

HPV testing — Human papillomavirus (HPV) is a virus that is responsible for the majority of cases of cervical cancer (see “Human papillomavirus” below). The procedure for HPV testing is identical to that of liquid based cytology testing. If HPV testing is done, it can be performed at the time of a Pap smear or later, using some of the liquid from a liquid based cytology test.

Screening women under age 30 for HPV is not recommended due to the large percentage of women in this age group that have transient (temporary) infections. Women aged 30 and older may elect, after discussion with their health care provider, to be screened for HPV in addition to having Pap smear testing; such women should be screened no more often than every three years.

Who should have a screening test?

Younger women — The first cervical cancer screening test is recommended within three years of first sexual activity or by age 21, whichever comes first. For most women, the test is recommended every one to three years, depending upon the woman’s age and history of abnormal results. For women who have a past history of an abnormal screening test or who have risk factors for cervical cancer, testing is recommended once per year (see “Cervical cancer risk factors” below).

Older women — Most experts feel that women who are at low risk for cervical cancer (eg, no past history of an abnormal test) can stop having cervical cancer screening tests by age 65 to 70 years. However, testing is recommended for women who are 65 years or older who have never been screened.

After hysterectomy — Women who have had a hysterectomy (surgical removal of the uterus and cervix) should not undergo screening for cervical cancer, unless:

The hysterectomy did not include removal of the cervix (eg, if the hysterectomy was “subtotal”)
The hysterectomy was performed because of cervical cancer or precancer
The woman was exposed to diethylstilbesterol (DES) during her mother’s pregnancy.
CERVICAL CANCER RISK FACTORS — The most important risk factor for cervical cancer is infection with the human papillomavirus (HPV). Other factors that increase the risk of cervical cancer include a history of multiple sexual partners, use of tobacco (eg, cigarettes), use of birth control pills, and a weakened immune system (eg, due to HIV infection or certain medications) (show table 1).

Human papillomavirus — Infection of the cervix with certain types of human papillomavirus (HPV) is the most significant risk factor for cervical abnormalities and cancer. Over 100 different types of HPV have been identified, however not all types infect the cervix or cause cancer. Researchers have labeled the HPV types as being high or low risk for causing cervical cancer. HPV types 6 and 11 can cause warts and are low-risk types because they rarely cause cervical cancer; types 16 and 18 are considered high-risk types because they may cause cervical cancer in some women. (See “Patient information: Condyloma (genital warts) in women”).

HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). It is not possible to become infected with HPV by touching an object, such as a toilet seat.

Most people who are infected with HPV have no signs or symptoms. Most HPV infections are temporary and resolve within two years. When the virus persists (in 10 to 20 percent of cases), there is a higher likelihood of developing cervical cell abnormalities and cancer. However, it usually takes many years for HPV infection to cause cervical cancer.

Sexual history — Cervical cancer is more common in women who have had more than one sexual partner or whose partners have more than one sexual partner.

Tobacco use — Smoking cigarettes increases the risk of cervical cancer and precancer by up to seven times that of women who do not smoke. Stopping smoking can decrease this risk. (See “Patient information: Smoking cessation”).

Birth control with estrogen — The risk of developing cervical cancer related to birth control is small, and is related to infection with HPV (show table 1). Thus, women who take a birth control with estrogen but are not infected with HPV have no increased risk of cervical cancer or precancer.

Weakened immune system — Women with a weakened immune system have a significantly increased risk of cancers and precancers of the cervix.

PAP SMEAR RESULTS — The information reported in a Pap smear is described in table 2 (show table 2A-B). Pap smear results may be reported as:

Negative — Pap smears that have no abnormal, precancerous, or cancerous cells are labeled as “Negative for intraepithelial lesion or malignancy”.

Smears that are negative can show other conditions, such as a vaginal infection (Trichomoniasis, yeast, herpes, or bacterial vaginosis) or cellular changes related to vaginal dryness, radiation therapy, or an intrauterine device (IUD) string. In some situations, further testing and/or treatment are needed.

Abnormal results — Cervical cells may appear abnormal for a variety of reasons. For example, a woman may have low estrogen levels or a cervical infection, or she may have a precancerous area or even cervical cancer.

A number of terms are used to describe abnormalities of the cervix, including:

Atypical squamous cells of undetermined significance (ASC-US)
Atypical squamous cells, cannot rule out a high grade lesion (ASC-H)
Low grade squamous intraepithelial cells (LSIL)
High grade squamous intraepithelial cells (HSIL)
Atypical glandular cells (AGC)
Carcinoma in situ (CIS)
Invasive cervical cancer
Follow up testing — A Pap smear is only a screening test. Further testing is needed after an abnormal Pap smear to determine whether cervical cancer or a precancerous cervical lesion is present. The need for further testing is described in detail in a separate topic review. (See “Patient information: Management of atypical squamous cells (ASC-US and ASC-H) and low grade cervical squamous intraepithelial lesions (LSIL)” and see “Patient information: Management of high grade cervical squamous intraepithelial lesions (HSIL) and glandular abnormalities (AGC)”).

CERVICAL CANCER PREVENTION

HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with four types of HPV (types 6, 11, 16, and 18). The vaccine was proven to be safe and effective in several large clinical trials [1,2] . A topic review is available that discusses the HPV vaccine. (See “Patient information: Human papillomavirus (HPV) vaccine”).

Sexual contact — Completely avoiding all sex or sexual contact is an impractical way to prevent infection with HPV. Condoms provide partial protection, but not complete protection because they do not cover all areas of the genitals. Having a limited number of sexual partners may reduce the risk of HPV infection.

Stop smoking — Women who smoke cigarettes are at increased risk of developing cervical cancer [3] . Women who smoke and have an abnormal Pap smear can reduce their risk of cervical cancer by quitting smoking. (See “Patient information: Smoking cessation”).

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)

American Society for Colposcopy and Cervical Pathology
(www.asccp.org)

American Cancer Society
(www.cancer.org, search for HPV)

National HPV and Cervical Cancer Public Education Campaign
Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)

Center for Disease Control and Prevention
(www.cdc.gov/)

American Social Health Association
(http://www.ashastd.org/)

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REFERENCES

1 Koutsky, LA, Ault, KA, Wheeler, CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347:1645.
2 Villa, LL, Costa, RL, Petta, CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 2005; 6:271.
3 Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 2006; 118:1481.
4 Wright, TC Jr, Cox, JT, Massad, LS, et al. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.
5 ACOG Practice Bulletin #66: Management of Abnormal Cervical Cytology and Histology. Obstet Gynecol 2005; 106:645.

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