Penile Human Papillomavirus Prevalence and Genotype Co-Detection Patterns in US Men: A Nationally Representative...

Human papillomavirus (HPV) surveillance often treats genotypes as independent events. However, shared host, behavioral, biological, and assay-related factors may produce non-independent genotype co-detection patterns. We quantified the burden and observed co-detection patterns of penile HPV in a nationally representative sample of US men to establish a descriptive reference for future surveillance. We analyzed men aged 18-59 years participating in the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Penile swabs were assayed using the Roche Linear Array. We estimated the population prevalence of multi-type burden, phenotype mixing (phylogenetic and carcinogenic), and co-detection estimates (observed-to-expected [O/E] ratios) for the most commonly observed genotype dyads and triads. Among 3374 men, the survey-weighted prevalence of any penile HPV was 44.1% (95% CI, 40.5-47.7). Co-detection was frequent. Among HPV-positive men, 46.0% (43.0-49.0) harbored genotypes from two or more alpha species groups. For common genotype dyads, co-detection consistently exceeded independence expectations (O/E range 1.84-4.11). The largest dyad O/E ratio was observed for HPV53 and HPV62 (O/E 4.11 [95% CI, 2.76-6.12]). Triad co-detection exceeded marginal-independence expectations, with O/E ratios reaching 27.53 for the combination of HPV6, HPV53, and HPV62. Among selected common dyads and triads, penile HPV co-detection in US men exceeded marginal-prevalence independence expectations. These reference estimates provide a descriptive baseline for future studies of changing genotype co-detection patterns.