Human papillomavirus 68 subtypes among people with human immunodeficiency virus and implications for anal screening

Human papillomavirus (HPV) infection is a key risk factor for anal cancer. While HPV16’s carcinogenic role is well established, the contribution of other high-prevalence genotypes in people with HIV (PWH), such as HPV68 is less defined. This study examines the prevalence of HPV68 subtypes, their oncogene expression, and association with histologically confirmed high-grade squamous intraepithelial lesions (HSIL). Two hundred PWH with abnormal anal cytology underwent HPV genotyping and mRNA analysis for the E6/E7 oncogenes of HPV16 and HPV68. Statistical analyses evaluated associations between HPV genotypes, oncogene expression, and HSIL. The cohort had a median age of 50 (IQR, 43-57) years, with 83% male participants and 93.9% virologically suppressed. HSIL was confirmed by histology in 25% of participants. HPV68 (28.5%) and HPV16 (24.5%) were the most prevalent genotypes, with HPV68a detected in 65.3% of HPV68-positive cases. Among HSIL cases, HPV16 (42%) and HPV68 (34%) were most common. HPV68a was significantly associated with HSIL in participants without HPV16. mRNA expression levels of E6 and E7 from HPV68a were significantly higher in the HSIL group (142.0 vs 12.9, p = 0.007 and 82.5 vs 9.1, p = 0.014, respectively). Differences remained significant after adjusting for the number of HPV genotypes and HPV16. These findings suggest that HPV68a drives anal HSIL and warrants inclusion in screening and vaccination for high-risk groups. Human papillomavirus (HPV) is a common virus that can lead to anal cancer. While HPV16 is already known to cause this cancer, less is known about the role of other HPV types. In this study, we screened the HPV types present in 200 people living with HIV who had abnormal anal cytology test results. We found that HPV68, particularly a form known as HPV68a, was common and associated with early tissue changes linked to anal cancer. These findings suggest that HPV68a may be important to consider in future screening programmes and vaccine development to better protect people living with HIV. This could improve the prevention and early detection of anal cancer in people at higher risk. Bello-Perez, et al. investigate the role of HPV68 in the development of anal high-grade squamous intraepithelial lesions (HSIL) among people living with HIV. Findings demonstrate an association between the HPV68a subtype and HSIL, which may have implications for future screening strategies and vaccination protocols.