Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
Am J Obstet Gynecol. 2017 Aug;217(2):183.e1-183.e11. doi: 10.1016/j.ajog.2017.03.022. Epub 2017 Mar 31.
Mortality associated with cervical cancer is a public health concern for women, particularly in HIV-seropositive women in resource-limited countries. HIV-seropositive women are at a higher risk of high-grade cervical precancer, which can eventually progress to invasive carcinoma as compared to HIV-seronegative women. It is imperative to identify effective treatment methods for high-grade cervical precursors among HIV-seropositive women.
Randomized controlled trial data are needed comparing cryotherapy vs loop electrosurgical excision procedure treatment efficacy in HIV-seropositive women. Our primary aim was to compare the difference in the efficacy of loop electrosurgical excision procedure vs cryotherapy for the treatment of high-grade cervical intraepithelial neoplasia (grade ≥2) among HIV-seropositive women by conducting a randomized clinical trial.
HIV-seropositive women (n = 166) aged 18-65 years with histology-proven cervical intraepithelial neoplasia grade ≥2 were randomized (1:1) to cryotherapy or loop electrosurgical excision procedure treatment at a government hospital in Johannesburg. Treatment efficacy was compared using 6- and 12-month cumulative incidence posttreatment of: (1) cervical intraepithelial neoplasia grade ≥2; (2) secondary endpoints of histologic cervical intraepithelial neoplasia grade ≥3 and grade ≥1; and (3) high-grade and low-grade cervical cytology. The study was registered (ClinicalTrials.govNCT01723956).
From January 2010 through August 2014, 166 participants were randomized (86 loop electrosurgical excision procedure; 80 cryotherapy). Cumulative cervical intraepithelial neoplasia grade ≥2 incidence was higher for cryotherapy (24.3%; 95% confidence interval, 16.1-35.8) than loop electrosurgical excision procedure at 6 months (10.8%; 95% confidence interval, 5.7-19.8) (P = .02), although by 12 months, the difference was not significant (27.2%; 95% confidence interval, 18.5-38.9 vs 18.5%; 95% confidence interval, 11.6-28.8, P = .21). Cumulative cervical intraepithelial neoplasia grade ≥1 incidence for cryotherapy (89.2%; 95% confidence interval, 80.9-94.9) did not differ from loop electrosurgical excision procedure (78.3%; 95% confidence interval, 68.9-86.4) at 6 months (P = .06); cumulative cervical intraepithelial neoplasia grade ≥1 incidence by 12 months was higher for cryotherapy (98.5%; 95% confidence interval, 92.7-99.8) than loop electrosurgical excision procedure (89.8%; 95% confidence interval, 82.1-95.2) (P = .02). Cumulative high-grade cytology incidence was higher for cryotherapy (41.9%) than loop electrosurgical excision procedure at 6 months (18.1%, P < .01) and 12 months (44.8% vs 19.4%, P < .001). Cumulative incidence of low-grade cytology or greater in cryotherapy (90.5%) did not differ from loop electrosurgical excision procedure at 6 months (80.7%, P = .08); by 12 months, cumulative incidence of low-grade cytology or greater was higher in cryotherapy (100%) than loop electrosurgical excision procedure (94.8%, P = .03). No serious adverse effects were recorded.
Although rates of cumulative cervical intraepithelial neoplasia grade ≥2 were lower after loop electrosurgical excision procedure than cryotherapy treatment at 6 months, both treatments appeared effective in reducing cervical intraepithelial neoplasia grade ≥2 by >70% by 12 months. The difference in cumulative cervical intraepithelial neoplasia grade ≥2 incidence between the 2 treatment methods by 12 months was not statistically significant. Relatively high cervical intraepithelial neoplasia grade ≥2 recurrence rates, indicating treatment failure, were observed in both treatment arms by 12 months. A different treatment protocol should be considered to optimally treat cervical intraepithelial neoplasia grade ≥2 in HIV-seropositive women.
宫颈癌相关死亡率是妇女健康的一个公共卫生关注点，尤其是在资源有限国家的 HIV 阳性妇女中。与 HIV 阴性妇女相比，HIV 阳性妇女患有高级别宫颈上皮内瘤变的风险更高，后者最终可能进展为浸润性癌。因此，迫切需要为 HIV 阳性妇女找到高级别宫颈前体病变的有效治疗方法。
需要随机对照试验数据来比较冷冻疗法与环形电切术治疗 HIV 阳性妇女的疗效。我们的主要目的是通过一项随机临床试验比较环形电切术与冷冻疗法治疗 HIV 阳性妇女高级别宫颈上皮内瘤变（≥2 级）的疗效差异。
18-65 岁患有组织学证实的≥2 级宫颈上皮内瘤变的 HIV 阳性妇女（n=166）按 1:1 比例随机（1:1）分为冷冻疗法或环形电切术治疗组，在约翰内斯堡的一家政府医院进行治疗。治疗 6 个月和 12 个月后，采用以下累积发生率来比较治疗效果：（1）宫颈上皮内瘤变≥2 级；（2）次要终点组织学宫颈上皮内瘤变≥3 级和≥1 级；（3）高级别和低级别宫颈细胞学。该研究已在 ClinicalTrials.gov 注册（NCT01723956）。
2010 年 1 月至 2014 年 8 月期间，166 名参与者被随机分配（86 名接受环形电切术治疗；80 名接受冷冻疗法治疗）。冷冻疗法组的 6 个月时累积宫颈上皮内瘤变≥2 级发生率（24.3%；95%置信区间，16.1-35.8）高于环形电切术组（10.8%；95%置信区间，5.7-19.8）（P=.02），但 12 个月时差异无统计学意义（27.2%；95%置信区间，18.5-38.9 vs 18.5%；95%置信区间，11.6-28.8，P=.21）。冷冻疗法组的 6 个月时累积宫颈上皮内瘤变≥1 级发生率（89.2%；95%置信区间，80.9-94.9）与环形电切术组（78.3%；95%置信区间，68.9-86.4）差异无统计学意义（P=.06）；12 个月时累积宫颈上皮内瘤变≥1 级发生率，冷冻疗法组更高（98.5%；95%置信区间，92.7-99.8），环形电切术组较低（89.8%；95%置信区间，82.1-95.2）（P=.02）。冷冻疗法组 6 个月时的高级别细胞学累积发生率（41.9%）高于环形电切术组（18.1%，P<.01）和 12 个月时（44.8% vs 19.4%，P<.001）。冷冻疗法组 6 个月时累积低级别细胞学或更高级别发生率（90.5%）与环形电切术组（80.7%）差异无统计学意义（P=.08）；12 个月时，冷冻疗法组的累积低级别细胞学或更高级别发生率（100%）高于环形电切术组（94.8%）（P=.03）。未记录到严重不良事件。
尽管 6 个月时环形电切术组的累积宫颈上皮内瘤变≥2 级发生率低于冷冻疗法组，但两种治疗方法在 12 个月时均显示出降低≥2 级宫颈上皮内瘤变的有效性，超过 70%。12 个月时两种治疗方法之间累积宫颈上皮内瘤变≥2 级发生率的差异无统计学意义。12 个月时，两种治疗组的高级别宫颈上皮内瘤变≥2 级复发率均较高，表明治疗失败。对于 HIV 阳性妇女的高级别宫颈上皮内瘤变，应考虑采用不同的治疗方案以达到最佳疗效。
