Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM

Abstract

Men who have sex with men (MSM) harbor the highest risk for anal carcinoma, mainly caused by Human Papillomavirus (HPV). The use of HPV-related biomarkers in the screening for this neoplasia is still debated. We assessed the association between high-risk (hr)HPV DNA, HPV16/18 DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 with cytological abnormalities (any grade) and high-grade intraepithelial lesions (HSIL) in HIV-uninfected and HIV-infected MSM. Overall, 150 cytological samples in PreservCyt (Hologic), with a negative to HSIL report, were analyzed for hrHPV DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 using the Linear Array (Roche), Aptima (Hologic), and CINtec® PLUS (Roche) assays. In HIV-infected MSM, positivity for all the biomarkers significantly increased with the cytological grade. In both populations, the association of hrHPV E6/E7 mRNA and p16/Ki-67 positivity with HPV16 did not differ significantly compared to hrHPVs other than HPV16. In HIV-uninfected MSM, the odds of having an HSIL increased approximately six times for the p16/Ki-67 positive cases. In HIV-infected individuals, all the biomarkers showed a significant association with HSIL, except for hrHPV DNA, with the strongest association observed for p16/Ki-67. The odds of HSIL increased almost 21 times in those positive for this biomarker. Our results encourage further investigation on the use of p16/Ki-67 dual staining in anal cancer screening for HIV-uninfected and HIV-infected MSM.