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

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.

Comparing Anal Cancer Screening Algorithms Using Cytology and HPV DNA Testing in Three High-risk Populations

Background Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. This study compares the screening performance of anal cytology to hrHPV DNA testing and two novel cytology/hrHPV cotesting algorithms among three high-risk populations. Methods Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1,837 participants comprising 1,504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women. Screening performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between four strategies with distinct HRA referral thresholds: cytology (ASCUS); hrHPV testing (any hrHPV+); algorithm A (benign cytology/HPV16/18+ or ASCUS/hrHPV+); and algorithm B (benign or ASCUS cytology/hrHPV+). Results Histological HSIL/cancer was detected in 756 (41%) participants. Cytology alone had the lowest sensitivity (0.76-0.89) but the highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For HIV-infected women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies and subgroups (range 0.16-0.36). Conclusions Screening algorithms that incoporate cytology and hrHPV testing significantly increased sensitivity and further decreased specificity to detect anal precancer/cancer among high-risk populations.