The Role of Enterococcus faecium in the Synergistic Clearance of High‐Risk HPV : A Clinical Study on Cervicovaginal Microbiota Regulation

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) is defined as the principal cause of cervical cancer. Given the important role of cervicovaginal microbiota in HPV acquisition and disease progression, this study aims to evaluate the clinical efficacy of the probiotic Enterococcus faecium (E. faecium) in synergistically promoting clearance of persistent HR-HPV infection. METHODS: We conducted a prospective clinical study involving 365 female patients with persistent HR-HPV infection. Following necessary anti-infective treatment, participants were allocated by their preference to one of three groups: an intervention group receiving E. faecium supplementation (n = 124), a regular follow-up group (n = 120), or a blank control group (n = 121). Their HR-HPV status and microecological parameters were assessed at 0, 6, and 12 months. Additionally, 24 participants were selected for 16S rRNA sequencing to analyze changes in the cervicovaginal microbiota composition during the follow-up period. RESULTS: Supplementation with E. faecium resulted in a significantly higher HPV clearance rate compared to the regular follow-up and control groups (55.65% vs. 29.17% vs. 13.22%, p < 0.001). Multivariate analysis confirmed that smoking (OR = 0.110, 95% CI 0.014-0.857, p = 0.035) and duration of persistent HPV infection (OR = 0.872, 95% CI 0.794-0.958, p = 0.004) were independent factors affecting HPV clearance. In the experimental group, the ecological shift was evidenced by a marked increase in the abundance of Lactobacillus (from 54.01% to 75.65%) and a significant reduction in several pathobionts, including Atopobium, Prevotella, and Staphylococcus (p < 0.001). Importantly, the abundance of Lactobacillus was substantially higher in HPV-negative individuals than in those with persistent infection (93.78% vs. 29.96%, p < 0.001). CONCLUSION: Our findings indicate that in women with persistent HR-HPV infection, E. faecium supplementation was associated with higher rates of HPV negativity and a shift toward a Lactobacilli-dominated vaginal microbiota, although causal relationships and underlying mechanisms require further investigation.