The Association Between Human Papillomavirus Type 16 E6 Seroprevalence and Degrees of Anal Disease Among Men With...

IntroductionHuman 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.MethodsA 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).ResultsHPV16 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.ConclusionsHPV16 E6 antibodies show poor sensitivity for anal cancer and its precursors, particularly among men with HIV.