Management of Cervical Neoplasia in Human Immunodeficiency Virus-Infected Women

The existence of cervical neoplasia in women with human immunodeficiency virus (HIV) represents one of the most serious challenges in the oncologic care of immunosuppressed patients. While the development of most cancers in the immunosuppressed patient can be attributed solely to immune deficiency, the relationship between squamous cell neoplasia of the cervix and HIV is quite unique because of common sexual behavioral risk factors. Screening strategies in HIV-positive women must take into account the high prevalence of cervical dysplasia in this subgroup as well as the limitations of cytologic screening. Cervical dysplasia in HIV-positive women may be of higher grade than in HIVnegative patients, with more extensive involvement of the lower genital tract with HPV-associated lesions. The presence and severity of cervical neoplasia in HIV-positive women correlate with both quantitative and qualitative Tcell function. Standard therapies for preinvasive cervical disease have yielded suboptimal results with high recurrence rates. While poor treatment results of standard ablative and excisional therapies warrant unique therapeutic strategies, one must recognize that close surveillance and repetitive treatment have been successful in preventing progressive neoplasia and invasive cervical carcinoma. The disease characteristics of invasive cervical carcinoma may take a more aggressive clinical course in HIV-infected women. HIVpositive women with cervical cancer have higher recurrence and death rates with shorter intervals to recurrence and death than do HIV-negative control subjects. CD4 status does influence subsequent outcome. In general, the same principles that guide the oncologic management of cervical cancer in immunocompetent patients should be applied. However, extremely close monitoring for both therapeutic efficacy and unusual toxicity must be instituted. [Monogr Natl Cancer Inst 1998;23:43‐49] Human immunodeficiency virus (HIV) infection continues to be a national and international health problem of epidemic proportions. Despite the fact that new acquired immunodeficiency syndrome (AIDS) cases increased by less than 5% for the fifth year in a row, a number well below the rate of increase in the epidemic’s first decade, the incidence of AIDS cases among women continues to increase, particularly in minority women. Approximately 19% of new adult and adolescent cases of AIDS in the United States last year were in women, and women represent the subgroup with the greatest rate of increase compared with any other defined population in North America. As with cervical neoplasia, HIV infection is largely a disease of women in their reproductive years, with the incidence of both diseases significantly higher in women of color. The existence of cervical neoplasia in women infected with HIV represents one of the most serious challenges in the oncologic care of immunosuppressed patients. While the development of most illnesses and cancers in HIV-infected patients can largely be attributed to immune deficiency, the relationship between cervical neoplasia and HIV infection is quite unique. Both cervical carcinoma and HIV infection are, in part, sexually transmitted diseases, with oncogenic types of human papillomavirus (HPV) infection the implicated viral carcinogen associated with cervical cancer. Therefore, an association between cervical cancer and HIV can be anticipated not only on the basis of immunosuppression but also because of shared common sexual behavioral risk factors. Thus, while immunosuppressed women, such as renal transplant patients receiving highly immunosuppressive drugs, are known to be at high risk for lower genital tract neoplasia, immunodeficient HIV-infected women are perhaps the highest risk subgroup that we know of. While these factors likely play the major role in the pathogenesis of cervical neoplasia in HIV-infected women, direct interactions between HIV and HPV at the molecular level, the effects of HIV on the local mucosal immune response, enhancement of HPV regulatory expression by the HIV-1 tat protein, and HIV-induced perturbations of paracrine or autocrine factors that influence HPV gene expression must also be considered.