Page 209 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

groups for this treatment modality. This is important in the context of personalized medicine and shared decision-making. The patient preference study was performed in collaboration with the Clinical Epidemiology and Medical Technology Assessment of the Maastricht University. The TOPIC3 study is a national multicenter study, in which we collaborate with the Erasmus MC and the Catharina Ziekenhuis Eindhoven. To generate awareness of our study results, all studies were submitted to international scientific journals and many have been presented at international congresses.
Schedule and implementation
This thesis provides evidence and tools for non-invasive management strategies in high- grade CIN, focusing on the prediction of spontaneous regression with prognostic biomarkers and immunotherapy with imiquimod. The results of this thesis could lead to the following implementations and future research opportunities.
- We recommend further research on prognostic biomarkers in high-grade CIN. This should be conducted according to the PROBE criteria for biomarker research, in order to improve interpretation, comparison and pooling of study outcomes. We believe that studies should aim for the development of biomarker panels or prediction models, in order to increase prognostic properties. Ideally, given the distinct difference in natural history of CIN2 and CIN3 lesions, prognostic markers should be studied in these groups separately.
- The prediction model and individual prognostic markers for spontaneous regression of CIN2 can be applied in clinical care, to improve individual patient counseling with regard to their chances of spontaneous regression. Furthermore, prognostic factors that can be influenced should be more actively addressed with patients. The results of our studies once again show the important effect of smoking. We therefore advocate that smoking cessation programs should be offered to smoking women with CIN2/3.
- The results of the inventory among gynecologists and the patient preference study, which show support for imiquimod as a treatment modality for high-grade CIN upon confirmation of its efficacy, serve as a justification for the performance of the TOPIC3 study and, hopefully, future clinical implementation of this treatment modality in specific patient groups.
- The TOPIC3 study will clarify the clinical applicability of imiquimod cream as a treatment modality for high-grade CIN. It will provide additional evidence on short- and long-term treatment efficacy, side effects and quality of life of imiquimod treatment. Upon the establishment of adequate treatment efficacy and clinical applicability, the results could support physicians and patients in a choice for imiquimod as treatment for high-grade CIN.
- A second aim of the TOPIC3 study is the identification of predictive markers for adequate treatment outcome. This could enable selection of women in whom an adequate response to imiquimod treatment is expected. To this aim, the biological mechanisms behind imiquimod-associated clearance of high-grade CIN should be further elucidated. An intended study by the authors on cervical TLR expression and the immune response to imiquimod in high-grade CIN could contribute to this issue.
- Other indications for imiquimod treatment of high-grade CIN may be large lesions requiring 207
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