Page 133 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Imiquimod: physicians’ awareness, attitudes and experiences
Introduction
Imiquimod is a toll-like receptor antagonist that has antiviral and antitumor properties. Imiquimod cream is currently registered for the topical treatment of certain types of basal cell carcinoma, actinic keratosis, and genital warts. It is also an effective treatment modality for HPV- induced vulvar intraepithelial neoplasia (VIN).[1] Indeed, imiquimod therapy is being applied in VIN in order to reduce potentially mutilating effects of surgical therapy and is recommended in current treatment guidelines.[2, 3]
Imiquimod has also been studied as a treatment modality for HPV-induced vaginal intraepithelial
neoplasia (VAIN) and cervical intraepithelial neoplasia (CIN), in order to reduce the side effects
and challenges associated with the standard treatment modalities for these conditions. At
present, advised treatment modalities for high-grade CIN include ablation or excision of the transformation zone or hysterectomy in selected patients with recurrent or persistent high-
grade CIN.[4] When treatment is indicated, this is usually performed by large loop excision of the transformation zone (LLETZ). LLETZ associates with moderately severe short-term side effects, 7 including prolonged bleeding and vaginal discharge. An important long-term side effect of LLETZ
treatment is a twofold increase in the risk of premature birth in subsequent pregnancies.[5, 6] For this reason, management by observation is recommended for young women with either CIN2 or CIN3 and adequate colposcopy.[4] The preferred treatment modalities for VAIN are surgical excision and laser ablation. However, VAIN treatment can be challenging as the lesions can be large and scattered. As a result, the rates of residual and recurrent VAIN after primary treatment are high.[7, 8]
Treatment efficacy of imiquimod in VAIN and CIN has been examined in several studies.[9-13] Although the patient populations and outcome measures in these studies were heterogeneous, the results were generally promising. One of these studies was a randomized controlled trial (RCT): it showed that in 22 out of 30 (73%) patients with high-grade CIN, imiquimod treatment caused histological regression to CIN 1 or less. However, side effects of vaginal application of imiquimod were common.[11]
Imiquimod is not currently registered for the treatment of VAIN and CIN and is not part of treatment guidelines. Additional studies on treatment efficacy and clinical applicability are currently conducted, but awareness and attitudes of physicians regarding imiquimod treatment for VAIN and CIN are unknown. In both research and clinical implementation of a new treatment modality, awareness and attitudes of physicians towards the treatment modality may be important factors for success. Additionally, knowledge on current off-label clinical experiences may provide valuable additional information on the clinical applicability of imiquimod in VAIN and CIN and perceived treatment indications.
This study aims to assess awareness, attitudes and current clinical experience of gynecologists with regard to imiquimod treatment of VAIN and CIN.
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