[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. 目的： 评估氨酮戊酸己酯光动力疗法（HAL-PDT）用于子宫颈上皮内瘤变2级（CIN2）的疗效及安全性。 方法： 研究数据来源于本研究团队于2020年10月至2023年7月开展的国际多中心、随机、双盲、安慰剂对照Ⅲ期临床试验（APRICITY研究），病历资料来源于全球7个国家的61个医疗中心。对其中组织病理学确诊的CIN2患者进行亚组分析。受试者按2∶1比例随机分配至HAL-PDT组［5%盐酸氨酮戊酸己酯软膏和发光二极管（LED）光源装置］或安慰剂组（安慰剂软膏和不产生光照的装置）。主要疗效指标为首次治疗后6个月的应答率。次要疗效指标包括组织学缓解率、高危型人乳头状瘤病毒（HR-HPV）转阴率。安全性评价指标为治疗相关不良事件（TRAE）发生率。 结果： 研究共纳入CIN2患者182例（HAL-PDT组120例、安慰剂组62例），两组受试者基线特征分别比较，差异均无统计学意义（P均>0.05）。HAL-PDT组6个月应答率（49.2%，59/120）和组织学缓解率（57.5%，69/120），均显著高于安慰剂组［分别为22.6%（14/62）、30.6%（19/62），P均=0.001］。HAL-PDT组6个月阴道镜下病灶清除率高于安慰剂组［分别为60.6%（60/99）、32.7%（17/52），P=0.001］。HAL-PDT组疾病进展风险呈下降趋势（RR=0.55，95%CI为0.29~1.06；P=0.068）。按年龄、HR-HPV感染状态、所在国家或地区和病变面积分层分析结果显示，应答率、组织学缓解率结果均一致支持HAL-PDT组获益。随访至12个月，HAL-PDT组HR-HPV转阴率显著提高：任何HR-HPV亚型转阴率为45.9%，HPV16转阴率为58.8%，HPV16/18转阴率为55.4%。HAL-PDT组与安慰剂组TRAE发生率差异无统计学意义［分别为31.1%（37/119）、25.8%（16/62），P=0.496］。HAL-PDT组最常报告的TRAE为阴道分泌物增多、腹痛和外阴阴道疼痛，均为轻度且具有自限性。 结论： HAL-PDT治疗CIN2患者显示出良好的疗效和安全性，可为有生育需求或希望保留子宫颈结构和功能的患者提供一种非手术治疗选择。.