Page 217 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

In 2017, a new national screening program for cervical cancer was introduced, based on primary HPV screening instead of primary cytological screening. As a consequence, most newly diagnosed CIN lesions are now high-risk (hr)HPV positive. The prediction model described in the previous chapter was developed in a population of both hrHPV-positive and –negative women, potentially making it less applicable in a population of exclusively hrHPV positive women with CIN2. Therefore, we aimed to identify prognostic factors for disease outcome in this subgroup of women, in chapter 6. We analyzed 9 potential prognostic factors in 56 women with hrHPV positive CIN2: HPV16/18 status, p16 staining, KI67 staining, age, smoking status, last PAP smear result, multiple CIN2 lesions, oral contraception use and parity. Not smoking and nulliparity were identified as significant prognostic factors for disease regression. These factors should be considered in individual patient counseling regarding the choice between immediate treatment or conservative management.
Assessment of clinical applicability of imiquimod cream as a non-surgical treatment modality for high-grade CIN
In order to assess clinical applicability of imiquimod in CIN, we first evaluated the knowledge, experiences and attitudes of physicians regarding imiquimod treatment of high grade CIN and the preferences of women with high grade CIN for either surgical or imiquimod treatment. As described in chapter 7, we sent a 37-item questionnaire to all Dutch gynecologists who regularly perform colposcopies. Of the 77 respondents, 58% were aware of imiquimod for treating CIN. Only five respondents had used imiquimod to treat CIN and reported generally successful treatment outcomes but frequent side effects. Among all respondents, 96% stated that they would consider using imiquimod to treat high-grade CIN in selected patients, but only upon additional evidence and inclusion into treatment guidelines. Patient preferences were assessed in chapter 8. A discrete choice experiment (DCE) was conducted among 100 women with abnormal cervical cytology in five hospitals in the Netherlands. Participants were asked to choose between imiquimod treatment or standard surgical treatment in nine separate scenarios, in which the treatment characteristics of both modalities were varied. The DCE showed that most women prefer LLETZ treatment over imiquimod. As expected, the choice for imiquimod treatment was influenced by a future pregnancy desire. Additionally, subgroup analyses revealed women with a future pregnancy desire accept a lower treatment efficacy of imiquimod than women without this desire, but a minimum treatment efficacy of 72% is still required. We concluded that imiquimod treatment does not seem appropriate for all women with high-grade CIN, but rather for a subgroup of women with a future pregnancy desire, in order to prevent surgical treatment with a risk of premature birth in subsequent pregnancy.
The current recommendation in the Dutch guideline on imiquimod treatment of CIN is based on one RCT. The implementation of a new treatment modality requires robust evidence of its efficacy. Indeed, our survey among gynecologists showed that additional evidence is wanted. For this reason, we designed the TOPIC trial, as described in chapter 9a. This was an RCT, designed to assess short and long-term efficacy of imiquimod treatment in high-grade CIN, as well as side effects and quality of life associated with the treatment modality. The study included three arms:
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