Cervical dysplasia and cancer are associated with human papillomavirus (HPV), a sexually transmitted virus. Carcinogenic strains of HPV, in conjunction with other factors, may cause dysplasia and cancer not only of the cervix, but also of the vulva, vagina, anus, and oropharynx. HIV-infected women have a higher prevalence of HPV infection than do HIV-uninfected women, and a higher prevalence of oncogenic HPV types. They are about 10 times more likely to develop cervical dysplasia, or squamous intraepithelial lesions (SIL), precursors to cervical cancer. Unfortunately, they also have a higher risk of invasive cervical cancer and tend to have more aggressive forms of cervical cancer and poorer responses to treatment. Invasive cervical cancer is an AIDS-defining illness.
The risk of high-grade cervical lesions appears to be higher for women with advanced immunodeficiency than for women with preserved CD4 cell counts. Other risk factors for dysplasia and cervical cancer include African-American ethnicity, a history of smoking, younger age at onset of sexual intercourse, and multiple sex partners. Effective antiretroviral therapy (ART) with immune reconstitution has not been shown to prevent the progression of dysplasia.
Screening for cervical dysplasia and appropriate intervention in women with high-grade dysplasia are effective in preventing cervical cancer. Frequent monitoring and careful follow-up in women with low-grade lesions are essential for preventing progression to invasive disease. Papanicolaou (Pap) testing should be performed routinely for all HIV-infected women, with testing initiated at the time of HIV diagnosis, repeated 6 months after the first test, then performed annually thereafter if the results are normal. (See chapter Initial and Interim Laboratory and Other Tests.)
Risk factors for candidiasis include diabetes mellitus and the use of oral contraceptives, corticosteroids, or antibiotics.
Because the risk of anal dysplasia also is increased among HIV-infected women (in some studies, rates of anal dysplasia were higher than rates of cervical dysplasia), many experts recommend concurrent screening for anal dysplasia. For further information, see chapter Anal Dysplasia.
For information on prevention of HPV infection, see "Prevention," below.
Patients with cervical dysplasia or early cervical cancer usually are asymptomatic and disease will not be diagnosed unless screening is performed. Genital condylomata (warts) indicate infection with HPV and typically are associated with low-risk types of HPV; however, a mixture of HPV types may be present, and women with genital warts may have concurrent dysplasia.
The classic symptom of early invasive cervical neoplasia is intermittent, painless bleeding between menstrual periods, which may present initially as postcoital spotting. Late symptoms of invasive cervical carcinoma include flank and leg pain, dysuria, hematuria, rectal bleeding, and obstipation.
Ask all female patients about risk factors for, previous history of, and preventive measures against cervical dysplasia and cancer, including the following:
Perform a focused examination of the abdomen and pelvis. Examine the external genital and perianal region. Perform speculum and bimanual examinations to evaluate the vagina and cervix. Look for lesions, masses, warts, and cervical inflammation or discharge, as well as exophytic or ulcerative cervical lesions with or without bleeding. Note that simple visual examination may not reveal abnormalities.
HIV-infected women have an increased risk of cervical dysplasia with progression to cervical cancer. If abnormalities of cervical disease are suspected, an appropriate evaluation should be performed. Because most women with cervical dysplasia have no symptoms, routine screening should be performed for all women.
Perform screening Pap test for all HIV-infected women. The initial test should be conducted at the time of HIV diagnosis, a second (if the first is normal) should be performed 6 months later. Screening should be repeated annually thereafter if all results are normal. (For HIV-uninfected women, recent guidelines from the American Congress of Obstetricians and Gynecologists recommend increasing the screening interval to 3 years if both Pap and HPV test results are negative; this screening strategy has not been shown to be safe and effective for HIV-infected women and is not recommended). If a Pap result is abnormal, see below. Also consider screening for anal dysplasia with an anal Pap test (see chapter Anal Dysplasia).
Cervical (and anal) cytology is graded using the Bethesda 2001 system (see "References," below), which categorizes disease in increasing order of severity as follows:
Other abnormalities may be noted, including the following:
If ASCUS is present without inflammation or suspected neoplastic process, several options for management exist.
Women with abnormalities suggestive of high-grade dysplasia should be referred for colposcopy.
Women with LSIL should be referred for colposcopy and directed biopsy.
Women with HSIL are at high risk of high-grade intraepithelial neoplasia or cervical cancer and should undergo colposcopy with endocervical assessment and directed biopsy as soon as possible. Refer to an oncology specialist for treatment.
Because of the high rate of significant lesions in patients with AGS, colposcopy with endocervical sampling is recommended for all subcategories, including AIS. In women over age 35, endometrial sampling is recommended in addition to colposcopy and endocervical sampling. Refer to an appropriate specialist for evaluation.
The optimal management of precancerous cervical lesions has not been identified clearly for all classes of SIL. Consult with an HIV-experienced gynecologist, oncologist, or other dysplasia specialist.
Latex or plastic barriers may block transmission of HPV in areas covered by these barriers, but infection may occur through bodily contact outside the area covered by the barriers. Nonetheless, their use is recommended to prevent transmission or acquisition of HPV.
Two vaccines have been approved by the U.S. Food and Drug Administration for the prevention of certain HPV strains in women:
Gardasil also has been approved for use with males of age 9-26 for prevention of genital warts; no data are available to evaluate efficacy in preventing cervical dysplasia or cancer in female partners.
These vaccines are not effective against HPV types other than those covered by the vaccine, and they may not be protective against a covered type to which a patient has been exposed previously.
The HPV vaccines have not been thoroughly studied in HIV-infected persons and thus are not specifically recommended for such patients; studies to evaluate efficacy, safety, immunogenicity, and tolerability are under way. The vaccines are not contraindicated for HIV-infected persons, and many clinicians do provide them. There are no data on the efficacy of the vaccines in preventing anal HPV; studies are under way.