Pap Smear

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INTRODUCTION — 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.

ANATOMY OF THE CERVIX — The cervix is located at the lower end of the uterus.

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. The transformation zone is the region most likely to contain abnormal cells.

  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.

•  Pap smear — The Pap smear (named after Dr. Papanicolaou) is a method of examining cells from the cervix. To perform the test, a healthcare provider uses an instrument (speculum) to view the cervix, which is located at the lower end of the uterus. The provider sweeps the surface of the cervix and inner cervix (called the endocervical canal) with a small spatula and a soft brush to collect cervical cells. This is not painful, although some women find the procedure uncomfortable. The brush or spatula is smeared onto a glass slide, sprayed with a fixative, and then sent to a laboratory for evaluation.

• 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.With liquid based cytology, the brush and/or spatula is placed into a vial containing a liquid preservative. The vial is sent to a laboratory for evaluation.

• HPV testing — Human papillomavirus (HPV) is a virus that is responsible for the majority of cases of cervical cancer. 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.

WHO SHOULD HAVE A SCREENING TEST?

Younger women — The first 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.

  Older women — Most experts feel that women who are at low risk for cervical cancer (eg, no past history of an abnormal test) can discontinue 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 SCREENING ACCURACY — Most cervical cancer screening tests can accurately identify women with abnormal cervical cells. However, the test is not perfect, and it misses between 5 and 25 percent of women with abnormalities. These women are said to have a false negative result. There are several important points to consider when discussing false negative results:

Many false negative results are the result of difficulty in collecting a sufficient number of cervical cells, not errors in reading the smear. It may be difficult to collect cervical cells if the cervix is hard to find during a pelvic examination, if the abnormal area is very small or high up inside the cervix, if only a few cervical cells are obtained, if the specimen dries too quickly, if the patient douches or has sexual intercourse before the examination, or if the woman is bleeding or has an infection at the time of the test.

If a woman has a normal result three years in a row, then it is unlikely that an abnormality has been missed. The frequency of screening for cervical cancer can then be spread out. If a new abnormality develops in a woman who is only tested every three years, it is likely to be found before it becomes serious because it takes years for a new abnormality to develop into a high-grade precancer or cervical cancer.

It usually takes many years for precancerous cervical cells to progress to cancer, and progression to cancer does not always occur; many precancerous abnormalities actually regress - that is, they return to normal on their own.

RISK FACTORS FOR CERVICAL CANCER — 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).

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.

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 rare in women who have never had sexual intercourse. Cervical cancer is more common in women who have had more than one sexual partner or whose partners have more than one sexual partner. Other risk factors include: HIV infection, sexual intercourse before age 17, or a history of sexually transmitted diseases (eg, genital herpes or Chlamydia).

Tobacco use — Smoking cigarettes increases the risk of cervical cancer and precancer by up to seven times that of women who do not smoke. This is believed to occur because cancer-causing products from tobacco are secreted into the cervical mucous. Stopping smoking can decrease this risk.

   Birth control with estrogen — Woman who use a birth control method that contain estrogen (eg, pills, patch) have a slightly higher risk of cervical precancers and cancers compared to women who do not take them. The risk of cervical cancer related to birth control is small, and is related to infection with HPV. Thus, women who take a birth control with estrogen but are not infected with HPV have no increased risk of cervical cancer or precancer.

The reason that oral contraceptives increase the risk of cervical cancer is not clear. Higher levels of estrogen may causes changes in the cervix that increase the growth of cells that develop as a result of the HPV infection.

However, birth control with estrogen has a number of benefits, including a reduced risk of ovarian and uterine cancer and decreased pain and bleeding with menstrual periods.

   Weakened immune system — Normally, the immune system works to protect the body from illness and infection, including the infection caused by human papillomavirus. Women with a weakened immune system have a significantly increased risk of cancers and precancers of the cervix.

A number of factors can weaken the immune system, including HIV infection, prolonged use of steroids (eg, prednisone), and use of medications to prevent rejection after organ transplantation.

PAP SMEAR RESULTS — 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.

• 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 medical terms are used to describe abnormalities of the cervix, including:

1. Atypical squamous cells of undetermined significance (ASC-US)
2. Atypical squamous cells, cannot rule out a high grade lesion (ASC-H)
3. Low grade squamous intraepithelial cells (LSIL)
4. High grade squamous intraepithelial cells (HSIL)
5. Atypical glandular cells (AGC)
6. Carcinoma in situ (CIS)
7. 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.

PREVENTING CERVICAL CANCER

HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with some types of HPV (types 6, 11, 16, and 18). The vaccine was proven to be safe and effective in several large clinical trials.

Sexual contact — Lifetime avoidance of 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.

Smoking cessation — Women who smoke cigarettes are at increased risk of developing cervical cancer. Cigarette smoking and HPV infection increase the risk of developing high-grade lesions. The risk of cervical cancer is increased two- to four-fold among cigarette smokers compared to nonsmokers.

Women who smoke and have an abnormal Pap smear can reduce their risk of cervical cancer by quitting smoking.