Prevalence of and Risk Factors for Anal High-grade Squamous Intraepithelial Lesions in Women Living with Human Immunodeficiency Virus

Abstract

Background Women living with human immunodeficiency virus (WLHIV) have disproportionately high rates of squamous cell carcinoma of the anus compared with the general population of women. Anal high-grade squamous intraepithelial lesions (HSILs) precede anal cancer, and accurate studies of HSIL prevalence among WLHIV in the United States are lacking. Methods The AIDS Malignancy Consortium 084 study was a multicenter national trial to evaluate the prevalence of and risk factors for anal HSIL in a US cohort. Eligible participants were WLHIV aged ≥18 years with no history of anal HSIL. Study participants had an examination including collection of cervical/vaginal and anal specimens, followed by high-resolution anoscopy with biopsy. Results We enrolled 256 women with evaluable anal pathology. The mean age was 49.4 years, 64% women were non-Hispanic black, 67% were former or current smokers, and 56% reported ever having anal sex with a man. The median CD4 T-cell count was 664 cells/μL. The prevalence of anal histologic HSIL (hHSIL) was 27% (95% confidence interval [CI], 22%–33%). There was a strong concordance (240/254) between local and consensus pathologists for hHSIL vs less than hHSIL (κ = 0.86 [95% CI, .79–.93]). Current CD4 count of ≤200 cells/μL was the strongest predictor of consensus anal hHSIL diagnosis (adjusted odds ratio [aOR], 10.34 [95% CI, 3.47–30.87]). History of anoreceptive intercourse was also associated with hHSIL (aOR, 2.44 [95% CI, 1.22–4.76]). Conclusions The prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy.

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia, and anal cancer in people living with HIV: a systematic review and meta-analysis

“…Among studies evaluating HSIL-AIN2+, one (4%) used cytology alone to diagnose HSIL+; 11 (48%) conducted HRA-directed biopsy on visible lesions, 8 (35%) conducted HRA among individuals with abnormal cytology with biopsies taken from visible lesions, and three (13%) studies took biopsies from individuals with both HRA-abnormal and normal findings. The highest scoring studies (≥5 on Newcastle-Ottawa scale, n=11) (30,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53) included random biopsy of normal quadrants and/or an independent verification of histology (Appendix, page 32-33). Restricting analyses to these studies did not change the estimates, although there was weak evidence that ART was associated with lower risk of HSIL-AIN2+.…”

“…All other authors declare no competing interests. (22, 23, 30-32, 34-36, 38, 41-43, 85-101) N populations 29 18 17 6 8 4 N PLHIV 7750 5311 4487 1107 2505 1745 ASCUS-AIN1+ prevalence (26-28, 32-35, 102-126) N populations 37 28 20 10 11 2 N PLHIV 8790 6782 5342 1720 2198 351 HSIL-AIN2+ prevalence (30,31,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(127)(128)(129)(130)(131)(132)(133)(134)(135)(136)(137) N populations 23 15 16 6 5 7…”

A 12-year retrospective evaluation of anal pre-cancerous lesions and cancer in people living with HIV-1 infection in the Southeastern U.S

“…HIV-infected men accounted for 96.0% of HSIL and 100% of AC cases in this study, while the study cohort consisted of 23% women. Recent studies among women living with HIV in US have reported the prevalence of anal HSIL to be 27% [ 19 ]. Our previous findings indicated that HIV-infected men had 7.9 times higher risk of incident anal HSIL (432 per 100,000 person-years), compared with HIV-infected women (55 per 100,000 person-years) [ 18 ].…”

“…Only 23.3% of AC patients had median CD4 counts ≥500 (cells/μL) (Table 1 ) suggesting that a large proportion did not have optimal immune status prior to cancer diagnosis. Lower CD4 count (≤200 cells/μL) is known to be a key factor in anal HSIL and cancer development [ 19 , 25 ]. While CD4+ could be a proxy for HIV status or treatment effect, there are no standard guidelines for anal HSIL treatment so that could not be assessed in the current study.…”

Brief Report: Recurrence of Anal High-Grade Squamous Intraepithelial Lesions Among Women Living With HIV

“…Notably, a recent national AIDS Malignancy Consortium (AMC084) trial study revealed that 28% of WLHIV have HSIL. 3 HSIL treatment using ablative therapies (i.e., infrared coagulation [IRC], electrocautery), topical treatments (i.e., 5% imiquimod or 5% fluorouracil cream) and continued surveillance, where HSIL recurrence may prompt further treatment, could prevent progression to SCCA. 4 Yet, to the best of our knowledge, recurrence rates (treatment effectiveness measure) among WLHIV remain unknown.…”