Prognostic value of p16-INK4A protein in women with negative or CIN1 histology result: a follow-up study

Int J Cancer. 2014 Feb 15;134(4):897-904. doi: 10.1002/ijc.28407. Epub 2013 Aug 29.

Abstract

P16-INK4A overexpression has been proposed as a prognostic marker to manage the follow up of women with positive cytology and/or HPV test but without high-grade cervical intraepithelial neoplasia (CIN2+). This study measures the relative risk (RR) of CIN2+ of p16 positive versus negative in these women. All the women referred to colposcopy from October 2008 to September 2010 with negative or CIN1 colposcopy-guided biopsy were included in the study; women surgically treated or having a CIN2-3 were excluded. All baseline biopsies were dyed with hematoxylin and eosin and p16. Women were followed up according to screening protocols, with cytology or colposcopy at 6 or 12 months. CIN2/3 RRs and 95% confidence intervals (95%CI) were computed. Of 442 eligible women, 369 (83.5%) had at least one follow-up episode. At baseline, 113 (30.6%) were CIN1, 248 (67.2%) negative, and 8 (2.2%) inadequate histology; 293 (79.4%) were p16-negative, 64 (17.3%) p16 positive and 12 (3.2%) not valid. During follow up, we found ten CIN2 and three CIN3; of these, six were p16 positive (sensitivity 46%, 95% CI 19-75). The absolute risk among p16 positives was 9.4/100 compared to 1.7/100 of the p16 negatives (RR 5.5; 95% CI 1.7-17.4). The risk was also higher for CIN1 than for histologically negative women (RR 4.4; 95% CI 1.3-14.3). The RR for p16 in CIN1 did not change (RR 5.2; 95% CI 0.6-47.5). P16 overexpression is a good candidate for modulating follow-up intensity after a negative colposcopy but is limited by its low prospective sensitivity.

Keywords: cervical cancer; cervical intraepithelial neoplasia; cohort study; colposcopy; p16; prognostic value; screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / virology
  • Adult
  • Biomarkers, Tumor / metabolism*
  • Carcinoma in Situ / epidemiology
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma in Situ / virology
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Cervical Intraepithelial Neoplasia / epidemiology
  • Cervical Intraepithelial Neoplasia / metabolism
  • Cervical Intraepithelial Neoplasia / pathology*
  • Colposcopy
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Papillomaviridae / pathogenicity
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Prognosis
  • Sensitivity and Specificity
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16