PMC

Infection with certain types of human papillomavirus (HPV) has been identified as a cause of cervical intraepithelial neoplasia and cervical cancer and possibly of other neoplasias of the lower genital tract in women. One of the risk factors for HPV infection and subsequent neoplasia and cancer of the lower genital tract is impaired cell-mediated immunity. Large observational studies involving HIV-positive women have shown a strong and consistent relation between coinfection with HIV and HPV and cervical intraepithelial neoplasia (CIN).,, It is therefore important for clinicians to screen patients who are HIV-positive women routinely for lower genital tract neoplasias and invasive cancer ().

HIV-positive women have significantly higher rates of CIN than do HIV-negative women., In one study, 7% of nearly 400 HIV-positive women had high-grade CIN, as compared with only 1% of 307 HIV-negative control subjects (p < 0.001). In another study, CIN was detected by cytological examination in 42% of 273 HIV-positive women and 8% of 161 HIV-negative women; half of the cases found in the HIV-positive group were high-grade lesions. Furthermore, it has been shown that HIV infection is a strong risk factor for cervical cancer,, independent of the usual demographic and behavioural risk factors for cervical cancer (). HIV-positive women with severe immunosuppression (defined as CD4+ cell count below 200 х 10⁶/L) are at greatest risk of CIN.,, Other risk factors in this cohort of women are age over 34 years, previous treatment of CIN and history of external genital warts.,,

Various strategies have been recommended to manage CIN in HIV-positive women (). In HIV-negative women, conservative therapies such as cryotherapy for low-grade CIN and loop electrosurgical excision for high-grade CIN are highly successful treatments, with over 80% cure rates. However, they are considerably less effective among HIV-positive patients. Rates of treatment failure within 3 years after treatment of CIN in this patient group have ranged from 38% to 62%, as compared with 18% among HIV-negative women.,, Recurrence rates have been particularly high, reaching 87% in one study involving HIV-positive women who had CD4+ cell counts of less than 200 х 10⁶/L. In a pilot study of adjunctive, self-administered maintenance therapy with intravaginal 5-fluorouracil (5-FU) cream after excisional treatment for high-grade CIN in HIV-positive women, the recurrence rate in the treatment group was nearly half that in the group not given the 5-FU cream (28% v. 47%). Although the side effects known to occur with intravaginal 5-FU therapy (e.g., vaginal erosions, adenosis and bloody discharge) were not encountered in this pilot study, our experience with this therapy suggests that this outcome was unusual.

The appropriate approach for screening and treating lower genital tract neoplasias in HIV-positive women is subject to debate. This is because of an incomplete understanding of their natural history in this patient population, especially with the advent of HAART. As has been suggested above, it is unclear whether HIV-positive women are truly at increased risk for invasive cervical cancer, although they clearly have a considerably higher prevalence of CIN than their HIV-negative counterparts. Cervical cytological examination to detect precancerous lesions is the most often used screening method among women, including those with HIV infection. Currently, the CDC and the US Public Health Service recommend that women undergo 2 Pap tests, 6 months apart, following the initial diagnosis of HIV infection (); if the results of both tests are negative, annual Pap tests are considered sufficient for routine screening., This strategy offers quality-adjusted life-expectancy benefits at a cost comparable to that of other clinical preventive interventions.