Clinical Efficacy, Safety, and Multi-Omics Insights of Capilliposide Vaginal Gel in CIN with High-Risk HPV: A Prospective, Multicenter Study

Background Cervical intraepithelial neoplasia (CIN) is a precursor of cervical cancer. This prospective, multicenter study evaluated the clinical efficacy, safety, and multi-omics characteristics of Capilliposide vaginal gel (CVG) in women with biopsy-confirmed CIN and high-risk human papillomavirus (HR-HPV) infection. Methods This prospective, multicenter, single-arm study enrolled 81 women with CIN 1/2/3 and HR-HPV infection. In Group 1, participants received CVG intravaginally every other day for 4 weeks to assess preliminary safety. Following the absence of significant adverse events, Group 2 was treated with CVG for 12 weeks to evaluate both safety and efficacy. Vaginal lavage and plasma samples were collected at baseline and 3 months post-treatment for microbiota analysis via 16S rRNA gene sequencing and plasma proteomics. Results Among the 67 participants who completed treatment, CVG was well tolerated, with no grade ≥ 2 or systemic toxicity. Cytological regression to negative for intraepithelial lesion or malignancy occurred in 82% of evaluable participants, and histologic regression was observed in 53.8% of paired biopsies. The overall HR-HPV clearance rates were 72.7% for HPV16 and 60.0% for HPV18. Multi-omics analysis showed a shift to a Lactobacillus-dominant vaginal microbiota and modulation of immune and epithelial repair pathways. Conclusions CVG as a safe, non-invasive, fertility-preserving treatment for CIN with HR-HPV infection, accompanied by changes in the vaginal microbiota and immune-related molecular pathways. Trial registration The trial was retrospectively registered on October 8, 2024, with the International Traditional Medicine Clinical Trial Registry (Registration No. ITMCTR2025002151), and the study has been completed.