Article Text

Download PDFPDF
  1. Stefania Cortecchia, PhD*,
  2. Giuseppe Galanti, MD*,
  3. Cecilia Sgadari, PhD,
  4. Silvano Costa, MD,
  5. Margherita De Lillo, PhD*,
  6. Licia Caprara, PhD*,
  7. Giovanni Barillari, MD§,
  8. Paolo Monini, PhD,
  9. Roberto Nannini, MD*,
  10. Barbara Ensoli, PhD and
  11. Lauro Bucchi, MD
  1. *Department of Pathology, Health Care District Hospital, Imola, Italy;
  2. National AIDS Center, Istituto Superiore di Sanità, Rome, Italy;
  3. Department of Obstetrics and Gynecology, St. Orsola Hospital, University of Bologna, Bologna, Italy;
  4. §Department of Experimental Medicine, University of Tor Vergata, Rome, Italy; and
  5. Romagna Cancer Registry, IRCCS IRST, Meldola, Forlì, Italy.
  1. Address correspondence and reprint requests to Lauro Bucchi, MD, Romagna Cancer Registry, IRCCS IRST, via Piero Maroncelli 40, 47014 Meldola, Forlì, Italy. E-mail: l.bucchi{at}


Objective The p16Ink4a (p16) tumor-suppressor protein is a biomarker for activated expression of human papillomavirus oncogenes. However, data are insufficient to determine whether p16 overexpression predicts the risk for progression of low-grade cervical intraepithelial neoplasia (CIN). This study was aimed at evaluating the risk for progression to CIN2 or worse during a 3-year follow-up of an unselected series of 739 patients with CIN1 biopsy specimens tested for p16 expression.

Methods Positivity of p16 was defined as a diffuse overexpression in the basal/parabasal cell layers. Selection biases were ruled out using a control group of 523 patients with CIN1 biopsies not tested for p16 expression. Analysis was based on the ratio of progression rates.

Results In the first year of follow-up, the 216 patients (29%) with p16-positive CIN1 had a higher progression rate (12.3%) than did the 523 patients with p16-negative CIN1 (2.2%) (rate ratio, 5.5; 95% confidence interval [CI], 2.59–11.71). In the second and third years, differences were smaller (rate ratio, 1.32 and 1.14, respectively) and not significant. The patients with p16-positive CIN1 also had a lower risk for regression to normal in the first year of follow-up (rate ratio, 0.55; 95% confidence interval, 0.42–0.71) and nonsignificant changes in the second and third years (rate ratio, 0.81 and 0.84, respectively).

Conclusions The patients with p16-positive CIN1 had an increased risk for progression that was concentrated in the first year of follow-up. Immunostaining of p16 could have a role in short-term surveillance of patients with CIN1. Further research should focus on midterm/long-term outcomes of p16-positive CIN1.

  • p16Ink4a
  • Cervical intraepithelial neoplasia
  • Progression
  • Regression

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.


  • Supported by the Italian Ministry of Health (Programma Straordinario di Ricerca Oncologica 2006).

  • The authors declare no conflicts of interest.