Page 155 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Patient preferences in treatment of high-grade CIN
Introduction
High-grade cervical intraepithelial neoplasia (CIN) is a relatively common condition and is considered to be the precursor of cervical cancer. It is usually caused by Human Papillomavirus (HPV)-infection of the uterine cervix.[1] Currently, the gold-standard treatment for high-grade CIN is surgical excision, which is usually performed by large loop excision of the transformation zone (LLETZ). Common side effects of LLETZ are postoperative haemorrhage and vaginal discharge. More importantly, LLETZ is associated with potentially serious long-term side effects. An approximately twofold increase in premature birth is seen in pregnancies after a LLETZ procedure.[2, 3] Recent evidence also suggests an increase in subfertility after LLETZ. A case- control study showed that women with a history of cervical treatment for CIN are at increased risk of subfertility defined as a time to conception of more than 12 months.[4]
Imiquimod cream (Aldara) has been studied as a non-invasive pharmacological treatment alternative in order to reduce pregnancy-related side effects of LLETZ.[5-7] Imiquimod is a toll-like
receptor antagonist with antiviral and antitumor properties. It is not currently registered for the
treatment of high-grade CIN and is not part of treatment guidelines, but it is widely used in HPV-
related vulvar intraepithelial neoplasia (VIN) with good results.[7] The rationale of imiquimod
treatment of HPV-induced lesions is to enhance the antiviral immunity of those who are unable
to clear HPV naturally. 8
Treatment efficacy of imiquimod in high-grade CIN has been studied in one randomized controlled trial RCT and shows promising results: treatment efficacy was reported in 73% of subjects compared to 39% in the placebo group.[5] In comparison, treatment efficacy of LLETZ treatment is higher, with 95% of patients being adequately treated.[8] Vaginal imiquimod can be self-administered by patients, but the treatment is time-consuming and side effects are common. Frequently reported side effects include vaginal pruritus and/or pain, vaginal discharge, and flu-like symptoms.[5, 9] Imiquimod, therefore, does not seem to qualify as a replacement for surgical treatment in all women. Nevertheless, subgroups may be identified for which imiquimod treatment does provide a good alternative. Our previous study has shown that gynecologists consider women who desire a future pregnancy and women with recurrent lesions as potential candidates for imiquimod treatment.[10]
The choice for either surgical treatment or pharmacological treatment with imiquimod for high- grade CIN is likely to be preference-sensitive. However, patients’ preferences for these treatment modalities are currently unknown. Knowledge of patients’ preferences and explanations for their preference may further aid the identification of subgroups of women for whom imiquimod treatment can be considered a good alternative to LLETZ treatment. The current study investigated patients’ preferences for either imiquimod or LLETZ in the treatment of high-grade CIN by means of a discrete choice experiment.
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