肯尼亚一项随机临床试验：冷冻疗法与环形电切术对伴有 HIV 及高级别宫颈病变的女性宫颈疾病复发的影响。
Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial.
机构信息
Department of Global Health, University of Washington, Seattle.
Department of Epidemiology, University of Washington, Seattle.
出版信息
JAMA. 2019 Oct 22;322(16):1570-1579. doi: 10.1001/jama.2019.14969.
IMPORTANCE
The World Health Organization recommends cryotherapy or loop electrosurgical excision procedure (LEEP) for histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2 or higher regardless of HIV status. Cryotherapy is more feasible in resource-limited settings but may be less effective for women living with HIV.
OBJECTIVE
To evaluate whether cryotherapy or LEEP is a more effective treatment for high-grade cervical lesions among women with HIV.
DESIGN, SETTING, AND PARTICIPANTS: Single-center randomized trial conducted among women with HIV and CIN grade 2 or 3. From June 2011 to September 2016, women with HIV in Kenya underwent cervical screening with Papanicolaou testing and confirmatory biopsy. The final date on which a study procedure was administered was September 7, 2016.
INTERVENTIONS
Women with HIV infection and CIN grade 2 or 3 were randomized 1:1 to receive cryotherapy (n = 200) or LEEP (n = 200) and were followed up every 6 months for 24 months with a Papanicolaou test and confirmatory biopsy.
MAIN OUTCOME AND MEASURES
The primary outcome was disease recurrence, defined as CIN grade 2 or higher on cervical biopsy, during the 24-month follow-up period.
RESULTS
Among 400 women who were randomized (median age, 37.4 [interquartile range, 31.9-43.8] years), 339 (85%) completed the trial. Over 2 years, 60 women (30%) randomized to cryotherapy had recurrent CIN grade 2 or higher vs 37 (19%) in the LEEP group (relative risk, 1.71 [95% CI, 1.12-2.65]; risk difference, 7.9% [95% CI, 1.9%-14.0%]; P = .01). Adverse events occurred in 40 women (45 events, including change in pathology and death due to other causes) in the cryotherapy group and in 30 women (38 events, including change in pathology and unrelated gynecological complications) in the LEEP group.
CONCLUSIONS AND RELEVANCE
In this single-center study of women with HIV infection and CIN grade 2 or 3, treatment with LEEP compared with cryotherapy resulted in a significantly lower rate of cervical neoplasia recurrence over 24 months. Cost-effectiveness analysis is necessary to determine whether the additional benefit of LEEP represents an efficient use of the additional resources that would be required.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01298596.
重要性
世界卫生组织建议对组织学确诊的宫颈上皮内瘤变（CIN）2 级或更高级别，无论 HIV 状况如何，均采用冷冻疗法或环形电切术（LEEP）进行治疗。冷冻疗法在资源有限的环境中更可行，但对 HIV 感染者的疗效可能较差。
目的
评估冷冻疗法或 LEEP 对 HIV 感染者的高级别宫颈病变是否更有效。
设计、地点和参与者：这是一项在肯尼亚开展的单中心随机试验，入组对象为 HIV 感染者和 CIN 2 级或 3 级患者。从 2011 年 6 月至 2016 年 9 月，肯尼亚的 HIV 感染者接受巴氏涂片检查和确认性活检进行宫颈筛查。最后一次进行研究程序的日期为 2016 年 9 月 7 日。
干预措施
HIV 感染且 CIN 2 级或 3 级的患者按 1:1 比例随机分为冷冻组（n = 200）或 LEEP 组（n = 200），并在 24 个月的随访期间每 6 个月接受巴氏涂片检查和确认性活检。
主要结局和测量指标
主要结局是 24 个月随访期间发生的疾病复发，定义为宫颈活检显示 CIN 2 级或更高。
结果
400 名随机分组的患者（中位年龄 37.4 岁[四分位距，31.9-43.8]）中，339 名（85%）完成了试验。在 2 年期间，冷冻组有 60 名（30%）患者发生了 CIN 2 级或更高级别的复发，而 LEEP 组有 37 名（19%）（相对风险，1.71 [95%CI，1.12-2.65]；风险差异，7.9% [95%CI，1.9%-14.0%]；P = .01）。冷冻组有 40 名患者（45 例事件，包括病理学改变和其他原因导致的死亡）和 LEEP 组有 30 名患者（38 例事件，包括病理学改变和无关的妇科并发症）发生了不良事件。
结论和相关性
在这项针对 HIV 感染且 CIN 2 级或 3 级的单中心研究中，与冷冻疗法相比，LEEP 治疗在 24 个月时显著降低了宫颈癌复发率。需要进行成本效益分析来确定 LEEP 的额外益处是否代表对所需额外资源的有效利用。
试验注册
ClinicalTrials.gov 标识符：NCT01298596。
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