Beyond cervicovaginal limitations: potential bidirectional interactions between HPV infection and mucosal microbiota from oral, anorectal and penile sites — a mini-review

Most existing studies focusing on human papillomavirus (HPV)-microbiota interactions are confined to the cervicovaginal tract, while mucosal microecological crosstalk at oral, anorectal and penile sites remains insufficiently summarized. This mini-review provides a narrative synthesis of current sequencing and epidemiological evidence regarding potential bidirectional interactions between HPV infection and site-specific mucosal microbiota across extra-cervicovaginal niches in both males and females. Oral HPV reshapes microbial composition in a sex-, race- and population-dependent manner; periodontal dysbiosis, high-risk HPV and Candida albicans jointly form a tripartite oncogenic axis that may contribute to oral squamous cell carcinoma, and periodontal inflammation independently elevates oral HPV susceptibility. Among men who have sex with men, pro-inflammatory anaerobes such as Bacteroides fragilis and Sneathia accumulate in anorectal HPV-related lesions, and concurrent HIV or sexually transmitted bacterial co-infections worsen mucosal dysbiosis and viral persistence. On penile skin, Corynebacterium is associated with a lower prevalence of HPV, whereas anaerobe-dominant community state types increase high-risk HPV risk, with HIV-induced baseline dysbiosis masking HPV-specific penile microbial signatures. Collectively, tissue-specific mucosal dysbiosis may represent an important co-factor linked to persistent HPV infection and subsequent malignant transformation. This review offsets long-standing sex-related and anatomical research bias, clarifies multi-site host-virus-microbe mechanisms, and provides theoretical support for developing microbiota-based biomarkers and microecological interventions to prevent non-cervical HPV-associated malignancies.