Five-year prospective evaluation of cytology, HPV testing, and biomarkers for detection of anal precancer in HIV+ MSM.

Background: Human papillomavirus (HPV)-related biomarkers have shown good cross-sectional performance for anal precancer detection in HIV-positive (HIV+) men who have sex with men (MSM). However, the long-term performance and risk stratification of these biomarkers are unknown. Here, we prospectively evaluated high-risk (HR) HPV DNA, HPV16/18 genotyping, HPV E6/E7 mRNA, and p16/Ki-67 dual stain in a population of HIV+ MSM.

Methods: We enrolled 363 HIV+ MSM between 2009-2010 with passive follow-up through 2015. All had anal cytology and high-resolution anoscopy at baseline. For each biomarker, we calculated the baseline sensitivity and specificity for a combined endpoint of high grade squamous intraepithelial lesion (HSIL) and anal intraepithelial neoplasia grade 2 or more severe diagnoses (HSIL/AIN2+), and we estimated the 2- and 5-year cumulative risks of HSIL/AIN2+ using logistic and Cox regression models.

Results: One hundred twenty-nine men were diagnosed with HSIL/AIN2+ during the study. HR-HPV testing had the highest positivity and sensitivity, but the lowest specificity of all assays. HPV16/18 and HPV E6/E7 mRNA had high specificity, but lower sensitivity. Two- and 5-year risks of HSIL/AIN2+ were highest for testing HPV16/18- or HPV E6/E7 mRNA-positive, followed by dual stain-positive. Testing HR-HPV- or dual stain-negative had the lowest 2- and 5-year risks of HSIL/AIN2+.

Conclusions: HPV-related biomarkers provide long-term risk stratification for anal precancers. HR-HPV- and dual stain-negativity indicate low risk of HSIL/AIN2+ for at least 2 years compared with negative anal cytology; however, the high positivity of HR-HPV in HIV+ MSM may limit its utility for surveillance and management in this population.