Topical imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia lesions (TOPIC-2): A randomised controlled trial

Anna J M van de Sande; Romy van Baars; Margot M Koeneman; Cornelis G Gerestein; Arnold-Jan Kruse; Edith M G van Esch; Peggy J de Vos van Steenwijk; Caroline L P Muntinga; Sten P Willemsen; Helena C van Doorn; Folkert J van Kemenade; Helene J van Beekhuizen

doi:10.1111/1471-0528.17808

Topical imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia lesions (TOPIC-2): A randomised controlled trial

BJOG. 2024 Mar 31. doi: 10.1111/1471-0528.17808. Online ahead of print.

Authors

Affiliations

¹ Department of Gynaecological Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, the Netherlands.
² Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, the Netherlands.
³ Division of Imaging and Oncology, Department of Gynaecological Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands.
⁴ Department of Obstetrics and Gynaecology, Isala Clinics, Zwolle, the Netherlands.
⁵ Department of Obstetrics and Gynaecology, Catharina Cancer Institute, Catharina Hospital, Eindhoven, the Netherlands.
⁶ GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
⁷ Department of Epidemiology, Erasmus MC University Medical Centre, Rotterdam, the Netherlands.
⁸ Department of Pathology, Erasmus University Medical Centre, Rotterdam, the Netherlands.

PMID: 38556619
DOI: 10.1111/1471-0528.17808

Abstract

Objective: To 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).

Design: Randomised controlled non-inferiority trial.

Setting: One academic and one regional hospital in the Netherlands.

Population: Thirty-five women with rrCIN were included in the study between May 2016 and May 2021.

Methods: Women 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 measures: The 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.

Results: Treatment 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.

Conclusions: This 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.

Keywords: cervical dysplasia; cervical intraepithelial neoplasia; efficacy; high‐grade squamous intraepithelial lesion; human papillomavirus; imiquimod; large loop excision of the transformation zone; prevention of cervical cancer; quality of life; transformation zone.