Optimize the Strategies in Cervical Low-grade Squamous Intraepithelial Lesions: 5-Aminolevulinic Acid Photodynamic Therapy and CO2 Laser

This prospective single-center non-inferiority trial evaluated a cost-effective hybrid protocol combining low-intensity CO₂ laser ablation (17 W, 2 mm depth) with abbreviated dual-session 5-aminolevulinic acid photodynamic therapy (PDT) for HPV-positive LSIL. 220 patients were allocated by preference to receive either combination therapy (n=110) or standard triple-session PDT monotherapy (n=110). Primary outcomes included histopathological regression and HPV clearance at 3 and 6 months. Combination therapy demonstrated non-inferiority in 3-month (82% vs 81%) and 6-month (87% vs 85%) regression rates (P<0.001), with comparable 6-month HPV clearance (76% vs 74%). Immunological analysis revealed significantly increased CD8+ T-cell infiltration and reduced pro-inflammatory cytokines in both groups. No severe adverse events were reported. This novel approach achieves equivalent clinical outcomes to standard triple-PDT while reducing treatment costs, through synergistic enhancement of antitumor immunity and inflammatory modulation. The results support its potential as a cost-effective alternative for LSIL management, pending multicenter validation of long-term efficacy.