Page 138 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 7
a larger patient population, 74 respondents (96%) stated that they would consider applying imiquimod in high-grade CIN. Thirteen respondents also commented on this question. Several respondents stressed that it is important that additional high-quality evidence of treatment efficacy becomes available; they also emphasized the need for additional research on the long- term effects, recurrence rates, and cost-effectiveness of imiquimod therapy for VAIN and CIN. Two respondents stated that imiquimod treatment would have to be incorporated in national guidelines on treatment of VAIN and CIN before they would apply it. One respondent commented that he/she would consider applying imiquimod in CIN 2 but not in CIN 3. Several respondents were concerned about the clinical applicability of imiquimod in CIN: they questioned whether the treatment would be tolerable for patients due to the common side effects, relatively long treatment duration, and practicalities such as the mode of application. One respondent stated that patient perspectives regarding imiquimod treatment for gynecological conditions should be researched further. Most respondents (n = 72, 94%) stated that they would consider participating in a RCT on the treatment efficacy of imiquimod in high-grade CIN.
Discussion
The current study shows that there is limited awareness among gynecologists in the Netherlands regarding investigational treatment of VAIN and CIN with imiquimod; this was especially true for CIN. A small number of respondents had used imiquimod as an off-label treatment for VAIN and CIN. The main reasons for their off-label application of imiquimod were recurrence of VAIN and CIN lesions, VAIN lesions that could not otherwise be optimally treated, and to avoid surgical treatment in patients with CIN who had a future pregnancy wish. The respondents reported good treatment efficacy but also stated that the side effects of imiquimod therapy were common. Nevertheless, all gynecologists who had treated patients with imiquimod stated that they would use this treatment modality again in the future. The attitude of gynecologists regarding imiquimod as a potential treatment of high-grade CIN is generally positive: a vast majority of participating gynecologists are willing to apply imiquimod for high-grade CIN, but recommend additional trials and subsequent inclusion of this therapy in CIN guidelines.
The limited awareness and clinical application of imiquimod in VAIN and CIN may be explained by the relative paucity of evidence regarding the efficacy of imiquimod treatment in VAIN and CIN and the fact that imiquimod treatment is not currently part of treatment guidelines. There are only three studies on the efficacy of imiquimod treatment in VAIN, and two of these focused on only or mainly low-grade lesions.[9, 13] The remaining study focused only on patients with high-grade lesions, but the patient population was small: disease regression was observed in six of the seven patients.[10] There are also only three studies on the efficacy of imiquimod in CIN. One of these was a recent RCT that showed 22 out of 30 (73%) patients with high-grade CIN exhibited disease regression after treatment.[11] The two other studies focused on different outcome measures or had a heterogeneous patient population.[12, 13] Large-scale RCTs that confirm treatment efficacy and assess disease recurrence over the long term are lacking. Additional evidence may lead to inclusion of imiquimod in treatment guidelines, leading to increased awareness and clinical application.
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