Page 163 - 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
treatment. The only RCT on imiquimod treatment of high-grade CIN showed a treatment success rate of 73% (defined as histologic regression to CIN 1 or less after 20 weeks from the beginning of treatment). Complete histologic regression was seen in 47% of patients.[5] Assuming a high risk of side effects and a low risk of subfertility and premature birth in clinical practice, our study showed that a treatment efficacy of 95% for imiquimod treatment is generally desired for women to derive a higher benefit from imiquimod treatment than from LLETZ treatment. This supports our notion that imiquimod therapy will not develop as a treatment alternative for the general population of women with high-grade CIN. However, we also showed that women who planned a future pregnancy would possibly accept a lower treatment success rate if the risk of subfertility and premature birth was low. In that case, a treatment success rate of 72% would result in women preferring imiquimod over LLETZ treatment. Additional evidence on the long-term treatment efficacy of imiquimod treatment should clarify whether a treatment success rate of at least 72% is actually achievable. Ideally, the individual probability of treatment success should be predictable. A combination of patient characteristics and biomarkers reflecting host, viral, and cellular factors may provide a model to make the individual response to imiquimod predictable.[16] Patients with higher chances of treatment success could then be identified and counselled based on the results of this study.
An important strength of this study includes the innovative aspect of the study subject: this is
the first study on patient preferences regarding the treatment of CIN. It provides the physician 8 with information on relevant attributes in the choice between imiquimod and LLETZ treatment
and on subgroups for who a new treatment modality might be indicated. Another strength is
the relatively large patient population, which is twice the size of the calculated sample size. The
moderate response rate of 56% can be considered a limitation of this study. Patients received
the questionnaire by mail and were asked to complete it before the colposcopy to prevent
biased results due to experiences during the colposcopy. Patients who had not completed the questionnaire at the time of the colposcopy could therefore not be included. Nevertheless, the
effect of a potential sampling or response bias as a result of low response rates seems limited in
other types of surveys.[17] Moreover, the study population is diverse with regard to age and future pregnancy plans, which are characteristics that could be expected to influence their treatment preference. Another potential limitation is the inclusion of the risk of subfertility as a treatment characteristic. A meta-analysis was published after the start of our DCE that concluded that there
is no evidence suggesting that treatment for CIN adversely affects fertility.[18] It must be noted,
however, that the results of this meta-analysis concerning time to conceive (subfertility) were
based on three studies, of which two were more than 20 years old. The only recent study indicates
a higher incidence of subfertility in women after LLETZ treatment.[4] Consequently, it cannot be
ruled out that the risk of subfertility is higher after LLETZ treatment.
In conclusion, women generally have a preference for LLETZ treatment of high-grade CIN. A preference for imiquimod treatment is influenced by the desire for a future pregnancy, in which case lower treatment success rates might be more acceptable as long as the risk of premature birth and subfertility are low. Additional evidence is necessary to confirm the safety and applicability of imiquimod treatment of high-grade CIN and should clarify the actual levels of treatment success and side effects.
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