Save the cervix: Treatment of primary and recurrent CIN: The role of imiquimod and LLETZ

The aim of this thesis was to investigate whether imiquimod is a viable treatment option in high-grade CIN. We focused on women with residual or recurrent lesions for whom imiquimod may be an alternative for LLETZ treatment, and without its associated long-term effects.
Part one focuses on assessing the applicability of imiquimod in primary CIN lesions. We found that most research has been performed in VIN. In research on imiquimod in CIN, histological regression to ≤CIN 1 was observed in 55% of imiquimod-treated women compared to 29% in the placebo group and 93% in those receiving surgical treatment. Looking at patient preferences, LLETZ was mostly preferred by patients, however also influenced by intentions regarding future pregnancies. However, also in women with wish to conceive, a minimum treatment efficacy of 72% was deemed necessary.
Part 2 focuses on recurrent or residual CIN and the role of imiquimod and LLETZ. In a retrospective database study we established a 61% success rate of a repeated LLETZ procedure and a 34% chance of additional procedures in follow up. A randomized controlled trial in treating women with recurrent or residual CIN(rrCIN) with either LLETZ treatment or imiquimod (TOPIC-2 trial) was stopped after inclusion of 35 patients in the pilot study. The treatment success rate was 33% in the imiquimod group compared to 100% in the LLETZ group (<0.001) according to intention-to-treat analysis, and 23% vs. 100% according to per protocol analysis. HPV clearance was also significantly lower in the imiquimod group compared to the LLETZ group (28% vs. 88%, p<0.001). This pilot study clearly established the futility of imiquimod.
The conclusion of our thesis is that LLETZ treatment should be the standard treatment in women with primary CIN and that imiquimod could be used in a subgroup. For rrCIN LLETZ should be the standard treatment and imiquimod should not be used.