Comparative Efficacy and Safety of Different 5-Aminolevulinic Acid Concentrations in Photodynamic Therapy for hrHPV-Related CIN2 with p16 Positivity: A Multicenter Randomized Controlled Trial

Persistent infection with high-risk HPV (hrHPV) is the primary cause of cervical cancer. Timely treatment of high-grade cervical intraepithelial neoplasia (CIN2/3) is essential to prevent cancer occurrence. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a minimally invasive treatment for CIN, preserving cervical structure and function. 119 patients were randomly assigned to placebo, ALA 500mg, or ALA 750mg groups. Each participant received six local treatments with ALA or placebo and red light exposure at 7-14 day intervals. Outcomes were evaluated at 24 weeks via hrHPV testing, cytology, colposcopy, and biopsy. At 24 weeks, ALA 500mg (90%, P=0.022) and 750mg (95%, P<0.001) groups showed significantly higher lesion regression rates than the placebo group (69.2%). HrHPV clearance rates were also higher in both ALA groups (67.5% vs 33.3%, P<0.001). ALA-PDT is a safe and effective treatment for hrHPV-related CIN2 with p16 positivity, with similar efficacy at both 500mg and 750mg concentrations.