Neuraminidase-Associated Vaginal Dysbiosis Correlates with HPV Infection Across Oncogenic Risk Subtypes

Human papillomavirus (HPV) infection is a major cause of cervical cancer, and increasing evidence suggests that cervicovaginal microbial dysbiosis may influence HPV susceptibility. This study evaluated the association between microbial enzymatic markers and HPV infection across different risk subtypes.

A cross-sectional analysis was conducted in 43,426 women undergoing HPV screening. HPV status and subtype classification (high-, possible-, and low-risk) were determined using standardized genotyping. Clinical and laboratory parameters including age, white blood cells (WBC), red blood cells (RBC), vaginal pH, leukocyte esterase, fungal infection, Trichomonas vaginalis, and microbial enzymatic markers (neuraminidase [NEU], N-acetylglucosaminidase [NAG], β-glucuronidase [GUS], and H₂O₂), were analysed.

HPV positivity was identified in 20.6% of participants. Neuraminidase emerged as the most consistent independent predictor across all HPV categories (adjusted OR range: 1.437-1.828; p<0.001), indicating a strong association between anaerobic bacterial activity and HPV infection. Age was uniformly associated with increased HPV risk across all models (adjusted OR ≈ 1.014-1.018 per year; p < 0.001). Fungal infection demonstrated a significant protective association (adjusted OR range: 0.636-0.778). Leukocyte esterase and WBC showed selective associations, particularly with high-risk HPV. In contrast, vaginal pH, T. vaginalis, and NAG lost significance after adjustment, suggesting confounding effects. Model explanatory power was modest (pseudo-R²: 0.010-0.016).

Neuraminidase-associated vaginal dysbiosis is strongly associated with HPV infection across multiple risk subtypes. These findings highlight the potential role of microbial functional biomarkers in understanding cervicovaginal dysbiosis and HPV susceptibility, particularly in populations vulnerable to microbial imbalance and secondary infections.