HIV+ women have several fold increased risk of invasive cervical cancer and precancerous cervical lesions, relative to the general population, as well as increased prevalence, incidence, and persistence of oncogenic human papillomavirus (oncHPV), the viral cause of cervical cancer. Each of these risks increases with diminishing CD4+. According to data from the Women's Interagency HIV Study (WIHS), the largest prospective US cohort of HIV+ and at-risk HIV- women, a quarter of HIV+ women at each clinic visit have abnormal Pap tests [ie, atypical squamous cells of undetermined significance or more severe (ASC-US+)]. Most of these abnormal Pap tests do not, however, reflect clinically relevant disease; i.e., cervical intraepithelial neoplasia grade 2 or more severe (CIN- 2+) by histology. USPHS guidelines currently recommend aggressive screening of HIV+ women: 2 Pap tests at 6 month intervals in the first year following diagnosis of HIV and, if normal, then on an annual basis. However, WIHS data have shown that HIV+ women with normal Pap tests who additionally co-test oncHPV- have a similar low 5-year risk of CIN-2+ and CIN-3+ as those who are HIV-. Conversely, HIV+ women who tested oncHPV+ despite a normal Pap had a 5-year cumulative risk of CIN-3+ of 4%. In multivariable Cox models, testing positive for non16- oncHPV was associated with a 3-fold increased risk of CIN-3+ relative to oncHPV-, whereas it was 13-fold for HPV16+, and 9-fold for those with LSIL by Pap (a benchmark for immediate colposcopy). Overall, HIV+ women with a normal Pap who test oncHPV- may not require screening for several years, whereas those who are HPV16+ may warrant immediate colposcopy, and those positive for other oncHPV have intermediate risk.
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