Page 117 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Introduction
High-grade cervical intraepithelial neoplasia (CIN 2-3) is caused by cervical infection with Human Papillomavirus (HPV) and is the precursor of cervical carcinoma. However, not all CIN lesions progress to cervical cancer. A significant subset of lesions regresses spontaneously without treatment.[1, 2] This is especially true for CIN2: studies have shown a spontaneous regression rate of up to 74% after 12 months follow-up.[3-6]
Most high-grade lesions, including CIN2, are treated by surgical excision, which is most commonly performed by large loop excision of the transformation zone (LLETZ). Given the rate
of spontaneous regression, this leads to significant overtreatment. This may result in unnecessary
side effects, such as continued bleeding, vaginal discharge and more importantly, a risk of premature birth in subsequent pregnancies.[7, 8] For this reason, international guidelines now 6 advice upon conservative management of younger women with CIN2.[9]
Ideally, the natural prognosis of an individual lesion would be predictable, to allow for selection of those women in whom spontaneous regression is to be expected. This would enable a more individualized management of CIN2. To this aim, several studies aimed to identify prognostic (bio) markers or prediction models for the natural history of CIN lesions. However, most studies were performed in mixed populations of CIN1/2 and CIN2/3 lesions and not exclusively CIN2 lesions.[6, 10-13] Those studies that did evaluate prognostic markers in exclusively CIN2, included both HPV positive and negative lesions.[4, 14-16] Since most screening programs for cervical cancer have recently switched to an HPV based approach, the majority of newly diagnosed CIN2 lesions will be high-risk (hr)HPV positive. As hrHPV in itself is considered to be a prognostic marker in CIN, this may alter the effect of other predictive markers on disease outcome in a population that is exclusively hrHPV positive.
Evidence on prognostic markers in exclusively hrHPV positive CIN2 is lacking, which hampers adequate counseling of patients with such lesions. For this reason, we designed the current study, which aims to identify prognostic factors for disease regression in hrHPV positive CIN2.
Materials and 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 were extracted from an existing database of a previous study by the authors.[17] In the previous study, patients were included with a biopsy proven CIN2 lesion who received observational management between January 1, 2000, and April 30, 2013. For the current study,
Prognostic factors for hrHPV positive CIN2
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