AIDS INFORMATION NEWSLETTER Michael Howe, MSLS, Editor AIDS Information Center VA Medical Center, San Francisco (415) 221-4810 ext 3305 March 22, 1996 Opportunistic Infections (Part XXII) Cervical Cancer (Excerpt from: Centers for Disease Control and Prevention. 1993 Revised Classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992;41(No.RR-17):[Inclusive page numbers].) Several studies have found an increased prevalence of cervical dysplasia, a precursor lesion for cervical cancer, among HIV- infected women (60, 61). In a study of 310 HIV-infected women attending methadone maintenance and sexually transmitted disease clinics in New York City and Newark, New Jersey, cervical dysplasia was confirmed by biopsy and/or colposcopy in approximately 22%, a prevalence rate 10 times greater than that found among women attending family planning clinics in the United States (Wright TC, personal communication; 62). Several studies have documented that a higher prevalence of cervical dysplasia among HIV-infected women is associated with greater immunosuppression (Wright TC, personal communication; 61,63). In addition, HIV infection may adversely affect the clinical course and treatment of cervical dysplasia and cancer (64-69). Invasive cervical cancer is a more appropriate AIDS-indicator disease than is either cervical dysplasia or carcinoma in situ because these latter cervical lesions are common and frequently do not progress to invasive disease (70). Also, cervical dysplasia or carcinoma in situ among women with severe cervicovaginal infections, which are common in HIV-infected women, can be difficult to diagnose. In contrast, the diagnosis of invasive cervical cancer is generally unequivocal. Invasive cervical cancer is preventable by the proper recognition and treatment of cervical dysplasia. Thus, the occurrence of invasive cervical cancer among all women--including those who are HIV-infected--represents missed opportunities for disease prevention. The addition of invasive cervical cancer to the list of AIDS-indicator diseases emphasizes the importance of integrating gynecologic care into medical services for HIV-infected women. References 60. Laga M, Icenogle JP, Marsella R, et al. Genital papillomavirus infection and cervical dysplasia--opportunistic complications of HIV infection. Int J Cancer 1992;50:45-8. 61. Schafer A, Friedmann W, Mielke M, Schwartlander B, Koch MA. The increased frequency of cervical dysplasia-neoplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression. Am J Obstet Gynecol 1991;164:593-9. 62. Sadeghi SB, Sadeghi A, Robboy SJ. Prevalence of dysplasia and cancer of the cervix in a nationwide Planned Parenthood population. Cancer 1988;61:2359-61. 63. Feingold AR, Vermund SH, Burk RD, et al. Cervical cytologic abnormalities and papillomavirus in women infected with human immunodeficiency virus. J Acquir Immune Defic Syndr 1990;3:896-903. 64. Maiman M, Fruchter RG, Serur E, Remy JC, Feuer G, Boyce J. man immunodeficiency virus infection and cervical neoplasia. Gynecol Oncol 1990;38:377-82. 65. Klein RS, Adachi A, Fleming I, Ho GYF, Burk R. A prospective study of genital neoplasia and human papillomavirus (HPV) in HIV-infected women (abstract). Vol.1. Presented at the VIII International Conference on AIDS/III STD World Congress, Amsterdam, The Netherlands, July 19-24, 1992. 66. Fruchter R, Maiman M, Serur E, Cuthill S. Cervical intraepithelial neoplasia in HIV infected women (abstract). Vol.1. Presented at the VIII International Conference on AIDS/III STD World Congress, Amsterdam, The Netherlands, July 19-24, 1992. 67. Richart RM, Wright TC. Controversies and the management of low-grade cervical intraepithelial neoplasia. Cancer (in press). 68. Rellihan MA, Dooley DP, Burke TW, Berkland ME, Longfield RN. Rapidly progressing cervical cancer in a patient with human immunodeficiency virus infection. Gynecol Oncol 1990; 36:435-8. 69. Schwartz LB, Carcangiu ML, Bradham L, Schwartz PE. Rapidly progressive squamous carcinoma of the cervix coexisting with human immunodeficiency virus infection: clinical opinion. Gynecol Oncol 1991;41:255-8. 70. Richart RM. Cervical intraepithelial neoplasia: a review. In: Sommers SC, ed. Pathology annual, 1973. New York:Appleton-Century- Crofts, 1973:301-28. Invasive Cervical Cancer CDC Training Bulletin Excerpt Question: Now that invasive cervical cancer has been added to the list of indicator illnesses for AIDS, can CDC recommend how often women who are HIV+ should have a pap smear? Answer: Recommendations for the medical management of HIV-infected women is not dependent on the addition of diseases, such as invasive cervical cancer, to the CDC AIDS case surveillance definition. The 1993 expanded AIDS case definition did not result in the reporting of many AIDS cases among women with a presenting diagnosis of invasive cervical cancer. PCP is still the leading AIDS-defining diagnosis among women reported with AIDS through June 1993. The November 30, 1990, edition of the MMWR contained a 1988 consensus recommendation from several organizations concerning how frequently women with and at risk for HIV infection should have Pap smears. Although personal physicians must make this decision based on risk factors for cervical cancer, the recommendation states that HIV-infected women should have a Pap smear annually. The American College of Obstetrics and Gynecology reiterated this information in their 1992 recommendations. (Centers for Disease Control and Prevention. Training Bulletin #62. August 23, 1993.) Cervical Cancer Screening for Women Who Attend STD Clinics or Who Have a History of STDs (Centers for Disease Control and Prevention. 1993 Sexually Transmitted Diseases Treatment Guidelines. 1993 Sept;42(No. RR- 14):[pages inclusive].) Women who have a history of STDs are at increased risk for cervical cancer, and women attending STD clinics may have additional characteristics that place them at even higher risk. Prevalence studies have found that precursor lesions for cervical cancer occur approximately five times more often among women attending STD clinics than among women attending family planning clinics. The Pap smear (cervical smear) is an effective and relatively low-cost screening test for invasive cervical cancer and squamous intraepithelial lesions (SIL)*, the precursors of cervical cancer. The screening guidelines of both the American college of Obstetricians and Gynecologists and the American Cancer Society recommend annual Pap smears for sexually active women. Although these guidelines take the position that Pap smears can be obtained less frequently in some situations, women who attend STD clinics or who have a history of STDs should be screened annually because of their increased risk for cervical cancer. Moreover, reports from STD clinics indicate that many women do not understand the purpose or importance of Pap smears, and many women who have had a pelvic examination believe they have had a Pap smear when they actually have not. Recommendations Whenever a woman has a pelvic examination for STD screening, the health-care provider should inquire about the result of her last Pap smear and should discuss the following information with the patient: o Purpose and importance of the Pap smear, o Whether a Pap smear was obtained during the clinic visit, o Need for a Pap smear each year, o Names of local providers or referral clinics that can obtain Pap smears and adequately follow up results (if a Pap smear was not obtained during this examination). If a woman has not had a Pap smear during the previous 12 months, a Pap smear should be obtained as part of the routine pelvic examination in most situations. Health-care providers should be aware that, after a pelvic examination, many women may believe they had a Pap smear when they actually have not, and therefore may report they have had a recent Pap sear. In STD clinics, a Pap smear should be obtained during the routine clinical evaluation of women who have not had a documented normal smear within the past 12 months. A woman may benefit from receiving printed information about Pap smears and a report containing a statement that a Pap smear was obtained during her clinic visit. Whenever possible, a copy of the Pap smear result should be sent to the patient for her records. FOLLOW-UP If a Pap smear shows severe inflammation with reactive cellular changes, the women should be advised to have another Pap smear within 3 months. If possible, underlying infection should be treated before the repeat Pap smear is obtained. If a Pap smear shows either SIL (or equivalent) or atypical squamous cells of undetermined significance (ASCUS), the woman should be notified promptly and appropriate follow-up initiated. Appropriate follow-up of Pap smears showing a high-grade SIL (or equivalent) on Pap smears should always include referral to a health-care provider who has the capacity to provide a colposcopic examination of the lower genital tract and, if indicated, colposcopically directed biopsies. Because clinical follow-up of abnormal Pap smears with colposcopy and biopsy is beyond the scope of many public clinics, including most STD clinics, in most situations women with Pap smears demonstrating these abnormalities will need to be referred to other local providers or clinics. Women with either a low-grade SIL or ASCUS also need similar follow-up, although some experts believe that, in some situations, a repeat Pap smear may be a satisfactory alternative to referral for colposcopy and biopsy. OTHER MANAGEMENT CONSIDERATIONS Other considerations in performing Pap smears are the following: o The Pap smear is not an effective screening test for STDs; o If a woman in menstruating, a Pap smear should be postponed and the woman should be advised to have a Pap smear at the earliest opportunity; o If a woman has an obvious severe cervicitis, the Pap smear may be deferred until after antibiotic therapy has been completed to obtain an optimum smear; o A woman with external genital warts does not require Pap smears more frequently than a woman without warts, unless otherwise indicated. SPECIAL CONSIDERATIONS PREGNANCY Women who are pregnant should have a Pap smear as part of routine prenatal care. A cytobrush may be used for obtaining Pap smears from pregnant women, although care should be taken not to disrupt the mucous plug. HIV INFECTION Recent studies have documented an increased prevalence of SIL among women infected with HIV. Also, HIV may hasten the progression of precursor lesions to invasive cervical cancer; however, evidence supporting such a progression is limited. The following provisional recommendations for pap smear screening among HIV-infected women are based partially on consultation with experts in the care and management of cervical cancer and HIV infection among women. These provisional recommendations may be altered in the future as more information regarding cervical disease among HIV-infected women becomes available: o Women who are HIV-infected should be advised to have a comprehensive gynecologic examination, including a Pap smear, as part of their initial medical evaluation. o If initial Pap smear results are within normal limits, at least one additional Pap smear should be obtained in approximately 6 months to rule out the possibility of false- negative results on the initial Pap smear. If the repeat Pap smear is normal, HIV-infected women should be advised to have a Pap smear obtained annually. o If the initial or follow-up Pap smear shows severe inflammation with reactive squamous cellular changes, another Pap smear should be collected within 3 months. o If the initial or follow-up Pap smear shows SIL (or equivalent) or ASCUS, the woman should be referred for a colposcopic examination of the lower genital tract and, if indicated, colposcopically directed biopsies. HIV infection is not an indication for colposcopy among women with normal Pap smears. *The 1988 Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses introduced the new terms low-grade squamous intraepithelial lesion (SIL) and high-grade SIL. Low-grad SIL encompasses cellular changes associated with HPV and mild dysplasia/cervical intraepithelial neoplasia 1 (CIN 1). High- grade SIL includes moderate dysplasia/CIN 2, severe dysplasia/CIN 3, and carcinoma in situ (CIS)/CIN 3 (16). [Note: For an overview of the management of HIV disease in women, see: Wofsy CB. Padian NS. Cohen JB. et al. Management of HIV Disease in Women. In: Volberding P. Jacobson MA., eds. AIDS Clinical Care 1992. New York: Marcel Dekker, Inc., 1992:301-328.] Editor's Note More information about women and HIV infection is included in the AIDS Information Newsletter series, Women and HIV Infection. This twenty-five part series was transmitted between June 3, 1994 and May 5, 1995 to all VA medical centers. The series (as well as other newsletter series) is available on the internet. Internet Access The AIDS Information Newsletter is emailed directly to the National Institute of Allergy and Infectious Diseases gopher site (gopher.niaid.nih.gov). Menu path is: 2. AIDS Related Information; 11. VA AIDS Information Newsletter. URL is: gopher://gopher.niaid.nih.gov/11/aids/vaain