Comparison of Treatment of Cervical Intraepithelial Lesions With Imiquimod or LLETZ

Summary

Purpose: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of treatment with LLETZ. LLETZ as standard treatment is possibly associated with premature labour, higher subfertility rate and a higher rate of spontaneous abortion. Since premature delivery is one of the most important causes of perinatal morbidity and mortality, alternative conservative methods for SIL treatment are constantly being evaluated. The immunomodulator imiquimod is one of the main target compounds for treating HSIL. Primary objective: to establish the efficacy of treatment with imiquimod (experimental arm) and compare it to the standard treatment with LLETZ (control arm). Secondary objective: * incidence and severity of the side effects in both groups; * need for treatment with LLETZ two years after primary treatment with imiquimod in the experimental arm or re-treatment with LLETZ two years after primary treatment with LLETZ in the control arm; * modulatory effect of imiquimod on immunoregulatory molecules. Study design: Single-centre randomized controlled intervention trial. Study population: 104 women with HSIL (52 in each arm). Intervention: \- randomization in two arms: 1. Experimental arm (imiquimod): treatment for 16 weeks with 5% imiquimod. 2. Control arm (LLETZ). Successful treatment in the experimental arm is defined as absence of histological HSIL in diagnostic biopsies at 20-week follow-up (4 weeks after treatment completion) and in the control arm successful treatment is defined as absence of cytological HSIL in cytology 6 months after LLETZ (same as in our national guidelines).

Timeline

Start

2018-11-20

Primary completion

2020-04-21

Completion

2023-09-15

Publications

• Background Grimm C, Polterauer S, Natter C, Rahhal J, Hefler L, Tempfer CB, Heinze G, Stary G, Reinthaller A, Speiser P. Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstet Gynecol. 2012 Jul;120(1):152-9. doi: 10.1097/AOG.0b013e31825bc6e8.
• Background de Witte CJ, van de Sande AJ, van Beekhuizen HJ, Koeneman MM, Kruse AJ, Gerestein CG. Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review. Gynecol Oncol. 2015 Nov;139(2):377-84. doi: 10.1016/j.ygyno.2015.08.018. Epub 2015 Aug 31.
• Background Koeneman MM, Kruse AJ, Kooreman LFS, Zur Hausen A, Hopman AHN, Sep SJS, Van Gorp T, Slangen BFM, van Beekhuizen HJ, van de Sande M, Gerestein CG, Nijman HW, Kruitwagen RFPM. TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC trial): study protocol for a randomized controlled trial. BMC Cancer. 2016 Feb 20;16:132. doi: 10.1186/s12885-016-2187-3.
• Background Jancar N, Mihevc Ponikvar B, Tomsic S. Cold-knife conisation and large loop excision of transformation zone significantly increase the risk for spontaneous preterm birth: a population-based cohort study. Eur J Obstet Gynecol Reprod Biol. 2016 Aug;203:245-9. doi: 10.1016/j.ejogrb.2016.06.005. Epub 2016 Jun 20.
• Cokan A, da Silva NCH, Kavalar R, But I, Pakiz M, Andrade de Oliveira S, Dos Santos Gomes FO, da Silva RS, Peixoto CA, Lucena-Silva N. Modulation of sHLA-G, PD-1, and PD-L1 Expression in Cervical Lesions Following Imiquimod Treatment and Its Association with Treatment Success. Cancers (Basel). 2024 Mar 25;16(7):1272. doi: 10.3390/cancers16071272.

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