Department of Obstetrics and Gynecology, Erasmus Medical Center Cancer Institute, Post box 2040, 3000, CA, Rotterdam, The Netherlands.
Department of Obstetrics and Gynecology, Maastricht University Medical Center, Maastricht, The Netherlands.
BMC Cancer. 2018 Jun 15;18(1):655. doi: 10.1186/s12885-018-4510-7.
Cervical dysplasia (cervical intraepithelial neoplasia (CIN)) is caused by Human Papillomavirus (HPV) and is most common in women of reproductive age. Current treatment of moderate to severe CIN is surgical. This procedure has potential complications, such as haemorrhage, infection and preterm birth in subsequent pregnancies. Moreover, 15% of women treated for high grade CIN develop residual/recurrent CIN or cervical cancer after surgical excision. Finally, 75-100% of patients with a residual and recurrent CIN 2-3 lesion are still HPV positive. They could possibly benefit from an alternative medical treatment, which aims to eliminate HPV. The primary study objective is to evaluate the effectivity of imiquimod 5% cream compared to treatment with Large Loop Excision of the Transformation Zone (LLETZ) for recurrent/residual CIN.
METHODS/DESIGN: This study is a multicentre, non-inferiority randomized single blinded study. The study population consists of female patients with histological proven residual/recurrent CIN after previous surgical treatment. Four hundred thirty-three patients will be included in the Netherlands. The first 35 patients will be included in a pilot study to prove non-futility. Included patients will be randomized to receive either 5% imiquimod cream or LLETZ treatment. Imiquimod will be inserted three times a week intravaginally for a period of 16 weeks using a vaginal applicator. Ten weeks after the end of imiquimod treatment a biopsy will be taken for treatment response. In case of progressive or stable disease a LLETZ will be performed. At 12 and 24 months after the start of treatment cytology will be taken for follow up. The LLETZ group will be treated according to the current guidelines. Throughout the study, HPV typing and quality of life will be tested.
Repeated LLETZ in women with residual/recurrent CIN lesions has complications. We would like to possibly offer alternative treatment in a selected group to avoid these risks. Moreover, we monitor treatment efficacy, side effects and long-term recurrence rates.
Medical Ethical Committee approval number: NL 53792.078.15. Affiliation: Erasmus Medical Center. Registration number ClinicalTrials.gov : NCT02669459 , date of registration: 27th January 2016.
宫颈发育不良（宫颈上皮内瘤变（CIN））由人乳头瘤病毒（HPV）引起，在育龄妇女中最为常见。目前对中重度 CIN 的治疗是手术。该手术有潜在的并发症，如出血、感染和随后妊娠的早产。此外，15%的高级别 CIN 手术后治疗的女性在手术切除后仍有残留/复发的 CIN 或宫颈癌。最后，75-100%的 CIN 2-3 病变残留和复发的患者仍为 HPV 阳性。他们可能受益于另一种旨在消除 HPV 的药物治疗。主要研究目的是评估咪喹莫特 5%乳膏与大环形电切术（LLETZ）治疗复发/残留 CIN 的疗效。
方法/设计：这是一项多中心、非劣效性随机单盲研究。研究人群为既往手术治疗后组织学证实有残留/复发 CIN 的女性患者。荷兰将纳入 433 例患者。前 35 例患者将纳入一项先导研究以证明无无效性。纳入的患者将随机接受咪喹莫特乳膏或 LLETZ 治疗。咪喹莫特每周三次阴道内插入，使用阴道给药器，持续 16 周。咪喹莫特治疗结束后 10 周进行活检以评估治疗反应。如果疾病进展或稳定，将进行 LLETZ。治疗开始后 12 和 24 个月取细胞学进行随访。LLETZ 组将根据现行指南进行治疗。在整个研究过程中，将检测 HPV 分型和生活质量。
在有残留/复发 CIN 病变的妇女中重复 LLETZ 有并发症。我们希望在选定的患者群体中提供替代治疗，以避免这些风险。此外，我们监测治疗效果、副作用和长期复发率。
医学伦理委员会批准号：NL 53792.078.15。隶属单位：伊拉斯谟医学中心。注册号：ClinicalTrials.gov：NCT02669459，注册日期：2016 年 1 月 27 日。
