Article Text

Download PDFPDF
Prognostic factors for spontaneous regression of high-risk human papillomavirus-positive cervical intra-epithelial neoplasia grade 2
  1. Margot M Koeneman1,2,
  2. Natasja Hendriks1,2,
  3. Loes FS Kooreman2,3,
  4. Bjorn Winkens4,5,
  5. Roy FPM Kruitwagen1,2 and
  6. Arnold J Kruse1,2,6
  1. 1 Department of Obstetrics and Gynecology, Maastricht University Medical Center, Maastricht, The Netherlands
  2. 2 GROW – School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
  3. 3 Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
  4. 4 Department of Methodology and Statistics, Maastricht University, Maastricht, The Netherlands
  5. 5 CAPRI – School for Care and Public health Research Institute, Maastricht University, Maastricht, The Netherlands
  6. 6 Department of Obstetrics and Gynecology, Isala Clinics, Zwolle, The Netherlands
  1. Correspondence to Dr Margot M Koeneman, Obstetrics and Gynecology, Maastricht University Medical Center, Maastricht 6227 HX, The Netherlands; margot.koeneman{at}


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.

  • CIN2
  • high-risk hpv
  • parity
  • prognosis
  • regression
  • smoking

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors All authors contributed to either study conception, design, data collection and processing, analyses, interpretation and/or the drafting/correcting of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data are available upon reasonable request.