ObjectiveTo investigate the efficacy of imiquimod in women with residual or recurrent cervical intraepithelial neoplasia (rrCIN), compared with large loop excision of the transformation zone (LLETZ).DesignRandomised controlled non‐inferiority trial.SettingOne academic and one regional hospital in the Netherlands.PopulationThirty‐five women with rrCIN were included in the study between May 2016 and May 2021.MethodsWomen were randomised to receive treatment with 5% imiquimod cream (12.5 mg) intravaginally (three times a week for a duration of 16 weeks) or a LLETZ procedure (standard treatment).Main outcome measuresThe primary outcome was reduction to normal cytology at 6 months after starting treatment. Secondary outcomes were clearance of high‐risk human papilloma virus (hr‐HPV) in both groups and reduction to ≤CIN1 in the imiquimod group. Side effects were monitored.ResultsTreatment success was 33% (6/18) in the imiquimod group versus 100% (16/16) in the LLETZ group (P < 0.001), whereas HPV clearance was 22% (4/18) in the imiquimod group versus 88% (14/16) in the LLETZ group (P < 0.001). After the randomisation of 35 women, the futility of treatment with imiquimod was proven and the trial was prematurely finished. In the follow‐up period, three patients remained without additional treatment, whereas all other patients underwent LLETZ, conisation or hysterectomy. In the LLETZ group none of the patients received additional treatment during 2 years of follow‐up.ConclusionsThis is the first randomised controlled trial to show that topical imiquimod has a significantly lower success rate in terms of reduction to normal cytology and hr‐HPV clearance, compared with LLETZ, in women with rrCIN. Additionally, imiquimod has numerous side effects and after using imiquimod most women with rrCIN still required additional surgical treatment.

中文翻译：

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局部咪喹莫特治疗残留或复发性宫颈上皮内瘤变病变（TOPIC-2）：一项随机对照试验

目的探讨咪喹莫特与变性区大环切除术（LLETZ）相比，对残留或复发性宫颈上皮内瘤变（rrCIN）女性的疗效。设计随机对照非劣效性试验。设置荷兰一家学术医院和一家地区医院。人口30 ‐2016 年 5 月至 2021 年 5 月期间，五名患有 rrCIN 的女性被纳入研究。方法女性被随机分配接受阴道内注射 5% 咪喹莫特乳膏（12.5 毫克）治疗（每周 3 次，持续 16 周）或 LLETZ 手术（标准治疗）。主要结局指标主要结局是开始治疗后 6 个月时细胞学降至正常。次要结果是两组的高危人乳头状瘤病毒（hr-HPV）均被清除，咪喹莫特组的CIN1降低至≤CIN1。监测副作用。结果咪喹莫特组的治疗成功率为 33% (6/18)，而 LLETZ 组的治疗成功率为 100% (16/16)（磷< 0.001)，而咪喹莫特组的 HPV 清除率为 22% (4/18)，而 LLETZ 组的 HPV 清除率为 88% (14/16)（磷< 0.001）。对 35 名女性进行随机分组后，证明咪喹莫特治疗无效，试验提前结束。在随访期间，三名患者未接受额外治疗，而所有其他患者均接受了 LLETZ、锥切术或子宫切除术。在 LLETZ 组中，没有患者在 2 年随访期间接受额外治疗。结论这是第一个随机对照试验，表明局部咪喹莫特在细胞学恢复正常和 hr-HPV 清除方面的成功率显着较低，与 LLETZ 相比，在患有 rrCIN 的女性中。此外，咪喹莫特有许多副作用，使用咪喹莫特后，大多数患有 rrCIN 的女性仍然需要额外的手术治疗。