Page 208 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 11
The role of imiquimod treatment in non-invasive management of high-grade CIN
A second strategy towards non-invasive treatment of high-grade CIN is the application of non- surgical treatment modalities. One non-surgical treatment modality is included in the Dutch treatment guideline for CIN: imiquimod, a cream with antiviral and antitumor properties. However, evidence regarding treatment efficacy and clinical applicability is scarce and clinical application is very limited. The studies in this thesis provide additional evidence on the desirability and clinical applicability of imiquimod as a treatment modality for high-grade CIN. First, we identified reasons for the currently limited application: this seemed to be the result of a lack of awareness among physicians, but also a perceived lack of evidence regarding treatment efficacy and a high rate of side effects. Subsequently, a patient preference study was conducted to assess the desirability of imiquimod treatment among women. This study indicated a subgroup of women with a future pregnancy wish as potential candidates for imiquimod treatment. These results show that there seems to be an area of indication for imiquimod in treatment of high- grade CIN, but additional evidence on treatment efficacy and side effects is necessary. The TOPIC3 study was designed to provide this evidence. The inclusions of this study have been completed and the results are expected in the spring of 2019. Upon confirmation of its efficacy and tolerability, the results of this study may increase the clinical application of imiquimod as an alternative to LLETZ, with the aim to reduce future premature birth as a side effect of surgical treatment.
Target groups
The results of this thesis are relevant for gynaecologists, pharmacists, high-grade CIN patients and research groups in the areas of prognostic biomarkers and imiquimod treatment of high-grade CIN. Application and development of prognostic biomarkers may improve individual patient counseling and management, reducing overtreatment of high-grade CIN. When the TOPIC-3 study confirms the clinical applicability of imiquimod as a treatment modality for high-grade CIN, it can be offered to women as an alternative to surgical treatment. Both strategies contribute to a reduction of surgical side effects, with the risk of future preterm birth as the most important.
Activities and innovation
We have provided a first overview of all previously studied prognostic biomarkers in high- grade CIN and further investigated two promising markers. These results can function as a tool for future biomarker research. For these studies, we collaborated with our colleagues at the Stavanger University Hospital in Norway, where a database and biopsy material is available from a cohort of women with high-grade CIN who were left untreated for a mean of 16 weeks. We developed a first prediction model for spontaneous regression of CIN2 and identified for the first time prognostic biomarkers for hrHPV positive CIN2, which may aid physicians in a more individual patient management. For these studies, we collaborated with the department of Clinical Epidemiology and Medical Technology Assessment of the Maastricht University. To assess the clinical applicability of imiquimod treatment, we not only started a clinical study on treatment efficacy and side effects of imiquimod in high-grade CIN, but we also performed an inventory among gynecologists and a patient preference study to assess the support among these
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