[Efficacy and safety of hexaminolevulinate photodynamic therapy for CIN2]

Objective: To evaluate the efficacy and safety of hexaminolevulinate photodynamic therapy (HAL-PDT) for the treatment of cervical intraepithelial neoplasia 2 (CIN2). Methods: Data of this study were derived from an international multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical trial (the APRICITY study) conducted between October 2020 and July 2023, with medical records obtained from 61 medical centers across 7 countries. A subgroup analysis was performed in patients with histologically confirmed CIN2 from this trial. Participants were randomly assigned in a 2∶1 ratio to the HAL-PDT group [5% hexaminolevulinate ointment and a light-emitting diode (LED) light source device] or the placebo group (placebo ointment with a non-illuminating device). The primary endpoint was the response rate at 6 months after the initial treatment. Secondary endpoints included histological regression rate, high-risk human papillomavirus (HR-HPV) clearance rate. Safety endpoints included treatment-related adverse events (TRAEs). Results: A total of 182 patients with CIN2 were included (120 in the HAL-PDT group, 62 in the placebo group). Baseline characteristics were balanced between the two groups (all P>0.05). At 6 months, the response rate [49.2% (59/120) vs 22.6% (14/62), P=0.001] and histological regression rates [57.5% (69/120) vs 30.6% (19/62), P=0.001] in the HAL-PDT group were significantly higher than those in the placebo group. The colposcopic lesion clearance rate at 6 months was also higher in the HAL-PDT group than in the placebo group [60.6% (60/99) vs 32.7% (17/52), P=0.001]. The risk of disease progression was lower in the HAL-PDT group (RR=0.55, 95%CI:0.29-1.06; P=0.068). Analyses stratified by age, HR-HPV infection status, region, and lesion size consistently demonstrated benefit in the HAL-PDT group regarding response and histological regression rates. At the 12-month follow-up, HR-HPV clearance rates in the HAL-PDT group were significantly improved, reaching 45.9% for any HR-HPV subtype, 58.8% for HPV 16, and 55.4% for HPV 16/18. There was no statistically significant difference in the incidence of TRAEs between the two groups [31.1% (37/119) vs 25.8% (16/62), P=0.496]. The most commonly reported adverse events in the HAL-PDT group were increased vaginal discharge, abdominal pain, and vulvovaginal pain, all of which were mild and self-limiting. Conclusion: HAL-PDT demonstrated favorable efficacy and safety in patients with CIN2, providing a non-surgical treatment alternative for patients seeking fertility preservation and the maintenance of cervical integrity.