Page 21 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman
P. 21

A last limitation of clinical application could be unwillingness of women to receive imiquimod 1 treatment. Indeed, although imiquimod treatment could potentially prevent side effects of
surgical treatment, the treatment modality has several important downsides. First, treatment
efficacy does not compare to the efficacy of LLETZ treatment. Second, imiquimod treatment is
more labor intensive and time consuming for patients than surgical treatment. Last, side effects of imiquimod treatment were very common and sometimes severe: almost all women treated with imiquimod experienced at least one side effect, among which were vulvar pain or pruritus, headache, myalgia, flu-like symptoms and vulvar erythema, erosion, edema or ulceration. Severe vulvar pain or pruritus was reported by 7% of women and severe flu-like symptoms by 13%. These treatment characteristics may influence the willingness of women to receive imiquimod treatment as an alternative to surgical treatment. It seems likely that imiquimod treatment will not be preferred by all women with high-grade CIN. Rather, those women with a future pregnancy desire may consider imiquimod treatment to prevent future obstetric complications. In the era of personalized medicine and shared-decision-making, patient preferences are considered increasingly important.[50] It is therefore essential to understand patient preferences with regard to the choice between imiquimod or surgery of high-grade CIN. A patient preference study could clarify which women would prefer imiquimod treatment instead of surgery, and at what terms.[51] Based on the above, additional evidence is necessary to assess the clinical applicability of imiquimod as a treatment modality for high-grade CIN, in the fields of treatment efficacy, physician awareness and attitudes, and patient preferences.
Aims of the current thesis
The aims of the studies described in this thesis are:
1. Assessment of clinical and molecular biomarkers as predictors of spontaneous regression of high-grade CIN lesions.
For this purpose, we first summarized the complex interaction between the immune system, viral factors and functional cellular mechanisms that determine the natural history of CIN lesions and conducted a review on prognostic biomarkers in high-grade CIN. This review is presented in chapter 2. Several biomarkers were identified that are associated with the natural history of high- grade CIN or can be regarded as promising in this regard. We further evaluated the prognostic properties of two of these biomarkers (HLA alleles and the chromosomal 3q26 locus). Chapter 3 describes the prognostic properties of HLA alleles in the natural history of high-grade CIN. Chapter 4 describes the prognostic properties of the chromosomal 3q26 locus in the natural history of high-grade CIN. Additionally, we aimed to identify biomarkers for the prediction of disease outcome in CIN2, to improve counseling of these patients for conservative management. Chapter 5 describes the development a prediction model for disease outcome of CIN 2. This prediction model is based on simple clinical parameters, reflecting patient and lesion characteristics, in order to provide with a widely applicable prediction model. After the development of this model, the hrHPV based screening method was implemented. As a consequence, nearly all CIN2 lesions are now hrHPV positive. We therefore aimed to identify prognostic factors in this subgroup of lesions as well, as described in chapter 6.
Introduction
 19

























































































   19   20   21   22   23