Page 139 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Imiquimod: physicians’ awareness, attitudes and experiences
Indeed, several respondents stressed the need for additional evidence regarding treatment efficacy, side effects, and long-term outcomes, and stated that they would only use imiquimod to treat VAIN and CIN when it was incorporated in the treatment guidelines.
An important limitation to the clinical application of imiquimod may be the high rate of side
effects of vaginal imiquimod therapy. All trials on vaginal imiquimod treatment and the current
study show high rates of side effects. These consist mainly of vaginal discharge, flu-like symptoms
and vulvar pain or pruritus, which were reported in up to 32%, 93% and 93% respectively in
previous trials on vaginal imiquimod for CIN lesions.[11, 12] Vulvar erosion or ulceration was seen
in up to 33% of patients treated with vaginal imiquimod. Flu-like symptoms and vulvar pain or
pruritus are not common side effects of LLETZ treatment, which is more common associated
with prolonged vaginal bleeding and vaginal discharge. An observational study in 185 patients
who underwent LLETZ treatment showed that 40% of women experienced moderate to severe
discharge and 50% experienced moderate to severe bleeding. Bleeding persisted for more than
two weeks in approximately 40% of women.[15] Intervention for postoperative hemorrhage is
rare: 7 cases (1.3%) were reported in a retrospective cohort study among 557 patients.[16] Indeed, 7 several respondents in the current study who had not used vaginal imiquimod expressed their
concern about its potential side effects. When choosing imiquimod therapy for VAIN or CIN, the side effects of standard treatment modalities should outweigh the side effects of imiquimod therapy, making imiquimod an acceptable treatment alternative. As such, imiquimod treatment may have to be limited to those patients who cannot be optimally treated by standard treatment modalities or in whom surgery is to be avoided. The latter group will consist mainly of younger patients with high-grade CIN and a future pregnancy wish. In order to reduce overtreatment, observation according to the ASCCP guideline should be considered first.[4] Imiquimod could be an alternative if treatment is preferred or upon disease persistence. This conclusion was clearly shared by the respondents in the current study who had used imiquimod to treat VAIN or CIN: they only used this treatment for VAIN lesions that could not be optimally treated by laser ablation or surgery, recurrent VAIN or CIN lesions, and patients with CIN lesions who had a future pregnancy wish and who would be at risk of premature birth if they underwent LLETZ treatment. Interestingly, the majority of our respondents underestimated the risk of premature birth in subsequent pregnancies. Moreover, a significant number stated that they do not discuss this risk with patients before LLETZ treatment. More widespread awareness of this risk could increase the clinical application of imiquimod after confirmation of its treatment modality and inclusion in treatment guidelines.
Treatment experiences in Dutch clinical practice were generally good. Off-label clinical application of imiquimod in VAIN and CIN was performed by a limited number of respondents, of whom the majority experienced successful treatment outcomes. Interestingly, our study also showed that there was a high rate of treatment discontinuation due to side effects. The incidence seems higher than that reported in previous trials, in which treatment discontinuation was very low. This discrepancy may reflect a better dosing regimen and response to side effects (with medication and dosing changes) in the clinical trials that arose from increased experience with this therapy. Quality of life studies or patient preference studies concerning vaginal imiquimod therapy are
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