Oral microbiome differences by race/ethnicity may contribute to differences in oral human papillomavirus (HPV) infection, the precursor to HPV-associated oropharyngeal cancer. Oral HPV is most prevalent among non-Hispanic Black individuals, yet HPV-attributable cancers are more common in non-Hispanic White individuals.

Using the 2009–2012 NHANES data (n = 5,534), our study examined oral microbiome diversity, community-, and taxon-level differences by any oral HPV type and race/ethnicity using oral rinse samples.

Significantly greater alpha diversity was seen among HPV-positive Non-Hispanic Black individuals [Shannon/Inverse Simpson’s Indices (p < 0.001)]. Beta diversity also varied significantly by race/ethnicity and oral HPV status (PERMANOVA, p < 0.001). Microbiome topic modeling identified two microbial communities (topics 13 and 36) depleted in HPV-positive individuals, characterized by reduced Streptococcus, Actinobacillus, and Neisseria (Beta > 0.4), but this pattern was seen only among Non-Hispanic Black individuals. Taxon-level differential abundance analysis identified Sneathia and Odoribacter as enriched in HPV-positive participants (p < 0.01).

These findings suggest a race/ethnicity-linked interplay between oral rinse microbiome samples and oral HPV. Microbial differences by race/ethnicity and oral HPV status may reflect underlying social, environmental, or behavioral factors and highlight the need for longitudinal studies to clarify causal pathways and inform future targeted interventions.