The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men

Background: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions (HSIL) in gay and bisexual men (GBM) in Sydney, Australia. Design: Baseline analysis of a 3-year cohort study Methods: The Study of the Prevention of Anal Cancer (SPANC) is natural history study of anal HPV infection in GBM aged ≥35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1), and dual cytology staining of p16 ^{INK 4a} /Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers. Results: The median age of the 617 participants was 49 years (range: 35–79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P<0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4% and 75.4% vs 83.2%, respectively), and improved specificity (68.0% and 69.4% vs 52.4%, respectively) and lower referral rates (47.0% and 45.0% vs 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3% vs 58.2%, P=0.005). Conclusion: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal HSIL with lower referrals in GBM than anal cytology.