Comparative Efficacy of Treatment Methods and Risk Factors for Treatment Failure in High-Grade Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis

Background: High-grade vaginal intraepithelial neoplasia (VaIN 2+) is a rare condition with limited evidence to guide optimal management. This study aimed to evaluate the efficacy of various treatment strategies and identify clinical risk factors associated with treatment failure. Methods: A systematic literature search in PubMed, Scopus, Web of Science, and Cochrane databases was performed following PRISMA guidelines. The meta-analysis included 15 retrospective studies including patients treated for VaIN 2+. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for treatment modalities (laser ablation, surgical excision, topical therapy) and clinical risk factors (prior hysterectomy, multifocality, immunosuppression, HPV16 infection and history of cervical intraepithelial neoplasia (CIN)). Results: Immunosuppression was significantly associated with a higher risk of treatment failure (RR = 2.01; 95% CI 1.12–3.60; p = 0.030). Topical therapies were found to have a significantly higher risk of treatment failure compared to laser ablation (RR = 1.92; 95% CI 1.34–2.92; p = 0.009). No statistically significant difference in recurrence risk was found between laser ablation and surgical excision, and between surgical excision and topical therapy. Factors such as prior hysterectomy, multifocality, and history of CIN did not show a statistically significant association with recurrence in the pooled models. Conclusions: Immunosuppression is a critical risk factor for VaIN 2+ recurrence, highlighting the need for individualized management and closer surveillance in this population. Surgical and ablative methods appear superior to topical agents in controlling high-grade disease. Given the retrospective nature of current data, standardized prospective studies are required to refine treatment algorithms.