Prognostic factors for spontaneous regression of high-risk human papillomavirus-positive cervical intra-epithelial neoplasia grade 2

INTRODUCTION: Since the implementation of human papillomavirus (HPV)-based screening for cervical cancer, the majority of cervical intra-epithelial neoplasia grade 2 (CIN2) lesions are high-risk (hr)HPV positive. Evidence on prognostic factors in hrHPV-positive CIN2 is lacking, hampering the individual counseling of women undergoing observation as routine management. The aim of this study is to identify prognostic factors for the spontaneous regression of hrHPV-positive CIN2.

METHODS: A retrospective cohort study was conducted at the Maastricht University Medical Center, the Netherlands. Women with hrHPV-positive CIN2 who underwent observation between January 1, 2000 and April 30, 2013 were included. Regression was defined as Pap 1/2 cytology (normal or atypical squamous cells of undetermined significance (ASCUS) cytology) or ≤CIN1 histology at the 24 month follow-up and no diagnosis of ≥CIN2 before the 24 month follow-up visit. Potential prognostic factors (HPV-16/18, p16 staining, KI67 staining, age, smoking status, last Pap smear result, multiple CIN2 lesions, oral contraception use, and parity) were assessed using logistic regression analysis.

RESULTS: A total of 56 women were included in the study, of which 34 (61%) showed spontaneous regression of their lesion. Of all studied potential prognostic factors, only not smoking and nulliparity were significantly associated with disease regression (OR 3.84, 95% CI 1.04 to 14.21, and OR 5.00, 95% CI 1.32 to 19.00, respectively, in the univariate analysis). Both effects remained significant after correction for age and HPV-16/18 in a multivariable regression analysis. In women who smoked, disease regression occurred in 10 of 22 women (46%), compared with 16 of 21 women (76%) who did not smoke. In parous women, regression occurred in 12 of 27 women (44%), compared with 16 of 20 nulliparous women (80%).

DISCUSSION: Smoking status and parity may influence the likelihood of disease regression in hrHPV-positive CIN2. These factors could be considered in individual patient counseling regarding the choice between immediate treatment or conservative management.