Genome-Wide Association Study of Persistent Anal Human Papillomavirus Infection Among HIV-Positive Males in Taizhou,...

The determinants of persistent human papillomavirus (HPV) infection remain largely unknown, and existing studies have predominantly focused on the female population. Individual genetic background may influence the persistence of HPV infection, we the evidence overall and among human immunodeficiency virus (HIV)-positive males are very limited. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with anal HPV persistence, based on a cohort designed to study the natural history of anal HPV infection among HIV-positive males in Taizhou, China from 2016 to 2022. A total of 322 HIV-positive males with anal HPV infection, with a mean age of 43.0 (standard deviation [SD]: 13.8) years, were included in this GWAS. The median follow-up time was 1.8 (interquartile range [IQR]: 1.5-2.0) years. The persistence of any type of HPV infection was 53.4%. After adjusting for age and sexual orientation, there were 2 SNPs with p < 1 × 10^-5 and 24 SNPs with p < 1 × 10^-4. The most closely associated with HPV persistence in additive models were rs7359031 (LOC105370461, odds ratio [OR]_T/C = 0.36, 95% confidence interval [CI]: 0.24-0.56; p = 6.67 × 10^-6) located at 14q21.1, and rs11046048 (PYROXD1, OR_C/A = 0.41, 95% CI: 0.28-0.60; p = 7.80 × 10^-6) located at 12p12.1. Other SNPs were mainly located at 6q23.3 (HBS1L-MYB) and 6p21.33 (CCHCR1, PSORS1C3). LOC105370461, PYROXD1, HBS1L-MYB, CCHCR1, and PSORS1C3 may be susceptible genes for HPV persistence. We appeal further studies to validate these associations and examine the underlying mechanisms.