The Association Between Human Papillomavirus Type 16 E6 Seroprevalence and Degrees of Anal Disease Among Men With HIV: A Nested Case Control Study

Introduction Human papillomavirus type 16 (HPV16) E6 antibodies may be an early biomarker of anal cancer. We cross-sectionally evaluated when in the course of anal disease, HPV16 antibodies are induced. Methods A nested case-control study of 846 men who have sex with men (MSM) was conducted within a prospective study of men with and without HIV. Cases of anal HPV16 (N=262), biopsy-confirmed high-grade squamous intraepithelial lesion (HSIL;N=140), and anal cancer (N=21) were individually matched to controls (N=423) on HIV status, study-participation duration, and age. Serum samples closest to diagnosis underwent HPV serologic testing; prediagnostic serial samples were tested for anal cancers only. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs). Results HPV16 E6 seroprevalence was non-significantly elevated in anal disease: OR:1.6 (95%CI:0.7-3.6) for HPV16 infection; OR:1.4 (95%CI:0.5-3.8) for HSIL; and OR:1.5 (95%CI:0.3-9.0) for anal cancer. HPV16 E6 seroprevalence was dramatically lower among men with versus without HIV with the same disease stage: 1.5% vs. 11.2% ( P <0.001) for anal HPV16 infection; 4.2% vs. 13.6% ( P =0.043) for HSIL; and 5.6% vs. 66.7% ( P =0.005) for anal cancer. HPV16 E6 seroprevalence was only associated with anal HPV16 among men without HIV (OR:2.9 [95%CI:1.0-8.0]); no significant associations between HPV16 E6 seroprevalence and anal disease were observed among men with HIV. Among the 21 anal cancers, 66.7% (2/3) without HIV and 5.6% (1/18) with HIV were HPV16 E6 seropositive before diagnosis. Conclusions HPV16 E6 antibodies show poor sensitivity for anal cancer and its precursors, particularly among men with HIV.