IMPORTANCE Persistence of cervical high-risk human papillomavirus (hrHPV) after treatment for cervical intraepithelial neoplasia grade 2 or higher (CIN2+) has not been compared between cryotherapy and loop electrosurgical excision procedure (LEEP) among HIV-positive women. OBJECTIVE To evaluate whether cryotherapy or LEEP is more effective at clearing hrHPV and whether persistent hrHPV is associated with CIN2+ recurrence among HIV-positive women. DESIGN, SETTING, AND PARTICIPANTS This is a secondary analysis of a randomized clinical trial conducted among women with HIV, hrHPV, and CIN2+ in Nairobi, Kenya. From June 2011 to September 2016, 354 HIV-positive women with CIN2+ disease had hrHPV cervical samples collected before and after treatment with cryotherapy or LEEP. Data were analyzed from September 2018 to January 2021. INTERVENTIONS Women were randomized 1:1 to receive cryotherapy or LEEP and were followed up every 6 months for 24 months with hrHPV cervical swab and Papanicolaou test with confirmatory biopsy. MAIN OUTCOMES AND MEASURES The main outcomes of this analysis were hrHPV positivity defined as having 1 of 12 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and disease recurrence defined as CIN grade 2 or higher as determined with cervical biopsy. RESULTS A total of 354 HIV-positive women with CIN2+ were included in the study; mean (SD) age was 37 (8) years in the cryotherapy arm and 38 (9) years in the LEEP arm. Baseline hrHPV prevalence was 90% (160 of 177) in the cryotherapy arm and 94% (166 of 177) in the LEEP arm (P = .24), and the most common hrHPV types detected were 16 (87 of 326 [27%]), 58 (87 of 326 [27%]), 35 (86 of 326 [26%]), 52 (66 of 326 [20%]), and 18 (56 of 325 [17%]). Over 24 months, clearance of hrHPV was significantly higher among those who underwent LEEP compared with cryotherapy (hazard ratio, 1.40; 95% CI, 1.03-1.90; P = .03). In multivariable analysis, hrHPV type-specific persistence at 12-month follow-up was significantly associated with CIN2+ recurrence from 12 months to 24 months (adjusted hazard ratio, 4.70; 95% CI, 2.47-8.95; P < .001). Performance of hrHPV testing at 12 months for recurrent CIN2+ was 93% sensitivity, 46% specificity, 38% positive predictive value, and 95% negative predictive value. CONCLUSIONS AND RELEVANCE In this secondary analysis of a randomized clinical trial, HIV-positive women who received LEEP were more likely to clear hrHPV infection compared with those undergoing cryotherapy, reinforcing the efficacy of LEEP in this population. Persistent hrHPV was significantly associated with recurrent CIN2+, suggesting that LEEP's benefits may be related in part to its ability to clear hrHPV infection. Screening for hrHPV infection after treatment among HIV-positive women may be used to rule out recurrent CIN disease given its high sensitivity and negative predictive value. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01298596.

中文翻译：

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HIV 阳性女性中冷冻疗法与环形电外科切除手术后人乳头瘤病毒的持久性及其与复发性宫颈上皮内瘤变的关联：随机临床试验的二次分析。


重要性尚未在 HIV 阳性女性中比较冷冻疗法和环形电切手术 (LEEP) 治疗 2 级或以上宫颈上皮内瘤变 (CIN2+) 后宫颈高危人乳头瘤病毒 (hrHPV) 的持续性。目的 评估冷冻疗法或 LEEP 在清除 hrHPV 方面是否更有效，以及持续性 hrHPV 是否与 HIV 阳性女性的 CIN2+ 复发相关。设计、环境和参与者 这是对在肯尼亚内罗毕感染 HIV、hrHPV 和 CIN2+ 的女性进行的一项随机临床试验的二次分析。从2011年6月到2016年9月，354名患有CIN2+疾病的HIV阳性女性在接受冷冻疗法或LEEP治疗之前和之后收集了hrHPV宫颈样本。数据分析时间为 2018 年 9 月至 2021 年 1 月。 干预措施 女性以 1:1 的比例随机接受冷冻疗法或 LEEP，并每 6 个月进行一次随访，持续 24 个月，使用 hrHPV 宫颈拭子和巴氏试验并进行验证性活检。主要结果和测量 该分析的主要结果是 hrHPV 阳性，定义为具有 12 种 hrHPV 类型中的一种（16、18、31、33、35、39、45、51、52、56、58、59），以及定义的疾病复发通过宫颈活检确定 CIN 2 级或以上。结果 共有 354 名患有 CIN2+ 的 HIV 阳性女性被纳入研究；冷冻治疗组的平均 (SD) 年龄为 37 (8) 岁，LEEP 组的平均 (SD) 年龄为 38 (9) 岁。冷冻治疗组中的基线 hrHPV 患病率为 90%（177 例中的 160 例），LEEP 组中的基线 hrHPV 患病率为 94%（177 例中的 166 例）（P = .24），检测到的最常见的 hrHPV 类型为 16 种（326 例中的 87 例 [27%] ]）、58 个（326 个中的 87 个 [27%]）、35 个（326 个中的 86 个 [26%]）、52 个（326 个中的 66 个 [20%]）和 18 个（325 个中的 56 个 [17%]）。 24 个月以来，与冷冻疗法相比，接受 LEEP 的患者 hrHPV 清除率显着更高（风险比，1.40；95% CI，1.03-1.90；P = .03）。在多变量分析中，12 个月随访时 hrHPV 类型特异性持续性与 12 个月至 24 个月的 CIN2+ 复发显着相关（调整后风险比，4.70；95% CI，2.47-8.95；P < .001）。 12 个月时 hrHPV 检测复发性 CIN2+ 的敏感性为 93%，特异性为 46%，阳性预测值为 38%，阴性预测值为 95%。结论和相关性 在这项随机临床试验的二次分析中，与接受冷冻治疗的女性相比，接受 LEEP 的 HIV 阳性女性更有可能清除 hrHPV 感染，从而增强了 LEEP 在该人群中的疗效。持续性 hrHPV 与复发性 CIN2+ 显着相关，表明 LEEP 的益处可能部分与其清除 hrHPV 感染的能力有关。鉴于其高敏感性和阴性预测价值，对 HIV 阳性女性治疗后进行 hrHPV 感染筛查可用于排除复发性 CIN 疾病。试验注册 ClinicalTrials.gov 标识符：NCT01298596。