Page 101 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman
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Introduction
High-grade cervical intraepithelial neoplasia (CIN 2-3, High-Grade Squamous Intraepithelial
Lesion, HSIL) is considered to be the precursor of cervical carcinoma. However, not all high-grade
CIN lesions will develop into cervical cancer; indeed, prospective follow-up studies show that a substantial subset of high-grade CIN lesions will regress spontaneously without treatment [1, 2].
Treatment guidelines have historically advised surgical treatment of high-grade CIN (CIN 2-3),
most commonly by large loop excision of the transformation zone (LLETZ). Since a substantial percentage of high-grade CIN lesions show spontaneous regression, this standardized treatment
policy leads to overtreatment and unnecessary complications as a result of surgical excision.
The most serious long-term complication of LLETZ is an increased risk of premature birth in subsequent pregnancies, most probably as a result of cervical insufficiency [3, 4]. Since CIN 2 has a 5 higher spontaneous regression rate than CIN 3, overtreatment is most profound for CIN 2 lesions
[5]. For this reason, conservative management of CIN 2 for young women was previously proposed by other authors [6]. International guidelines also advocate conservative treatment of younger women with CIN 2 [7, 8]. As a result, LLETZ rates have decreased in patients with CIN 2 histology preceded by low-grade abnormal cytology [9].
Ideally, those lesions that will regress spontaneously should be differentiated from those that will not, allowing for watchful waiting instead of invasive treatment in the subgroup of patients in which spontaneous regression is expected. Prediction of the individual probability of regression of high-grade CIN is essential for this strategy. Conventional histopathological assessment is unfit for this purpose. Several patient and biopsy characteristics and immunological or histological biomarkers have been identified that correlate with prognosis in high-grade CIN, but no biomarker or biomarker profile has yet reached clinical applicability [10]. This study aims to develop a widely applicable prediction model for spontaneous regression of CIN 2 lesions based on patient and lesion characteristics, as these are simple and readily available clinical parameters.
Methods
Setting
This registration-based retrospective cohort study was conducted at the Maastricht University Medical Center, Maastricht, the Netherlands. Approval for this study was obtained from the Medical Ethics Committee of Maastricht University Medical Center (approval number: METC 15- 4-174; September 2, 2015).
Population
Patients with a diagnosis of CIN 2 from a diagnostic biopsy obtained during a colposcopy who received observational management (including cytological follow-up) between January 1, 2000 and April 30, 2013 were retrospectively identified and assessed for eligibility. According to the colposcopy protocol, biopsies were taken from each suspicious lesion. The histopathological assessment of cervical biopsies was performed according to national guidelines, based on the World Health Organization criteria, with p16 staining in case of an inconclusive diagnosis based
A prediction model for CIN2 prognosis
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