Efficacy and safety of photodynamic therapy for vaginal intraepithelial neoplasia: A systematic review and meta-analysis

• Systematic reviews and meta-analyses confirm that5-aminolevulinic acid photodynamic therapy (ALA-PDT) is effective in treating vaginal intraepithelial neoplasia (VaIN), with a lesion clearance rate of 77.8%–95.2%. • ALA-PDT can efficiently clear high-risk HPV (12-month clearance rate of 85.7%) and has mild adverse reactions, significantly reducing the risk of recurrence of VaIN. • Compared to CO₂ laser, ALA-PDT better preserves vaginal structure and function, making it particularly suitable for elderly and multifocal VaIN patients and those with fertility preservation needs. • This research systematically reviews clinical outcome data on 5-aminolevulinic acid photodynamic therapy ALA-PDT for VaIN. Based on this review, it provides evidence-based guidance for selecting minimally invasive treatment options for VaIN. Vaginal Intraepithelial Neoplasia (VaIN) is a precancerous condition that can progress to vaginal cancer if untreated. Photodynamic Therapy (PDT), recognized for its minimally invasive nature and favorable side effect profile, is increasingly employed for VaIN treatment; however, comprehensive evidence synthesis on its efficacy and safety remains limited. This study aims to comprehensively evaluate the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in treating VaIN. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies evaluating PDT efficacy in VaIN. Primary outcomes were complete response (CR) rate and HPV clearance rate; secondary outcomes included recurrence rate and adverse events (AE). Meta-analysis was performed using Stata 18.0. Nine trials (421 patients) were included. Pooled outcomes: 6-month CR:87% (95% CI: 78%-94%), 12-month CR:84% (95% CI:76%-91%); 6-month HPV clearance:61% (95% CI:55%-66%), 12-month:73% (95% CI:67%-78%); 6-month HPV16/18 clearance:71% (95% CI:61%-80%), 12-month:76% (95% CI:63%-88%); 6-month recurrence:4% (95% CI:2%-8%), 12-month:7% (95% CI:0%-24%); AEs: Increased vaginal discharge (20%, 95% CI: 8%-36%), itching (25%, 95% CI: 1%-62%), burning sensation (23%, 95% CI: 1%-57%), abdominal pain (7%, 95% CI: 0%-21%), and mild vaginal bleeding (0%, 95% CI: 0%-3%). No serious AEs. ALA-PDT demonstrates high efficacy and favorable safety in treating VaIN. However, as current evidence primarily stems from single-arm studies, future high-quality multicenter randomized controlled trials are essential to confirm these findings and directly compare ALA-PDT with standard therapies.