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.
*Department of Pathology, Health Care District Hospital, Imola, Italy; †National AIDS Center, Istituto Superiore di Sanità, Rome, Italy; ‡Department of Obstetrics and Gynecology, St. Orsola Hospital, University of Bologna, Bologna, Italy; §Department of Experimental Medicine, University of Tor Vergata, Rome, Italy; and ∥Romagna Cancer Registry, IRCCS IRST, Meldola, Forlì, Italy.
Address correspondence and reprint requests to Lauro Bucchi, MD, Romagna Cancer Registry, IRCCS IRST, via Piero Maroncelli 40, 47014 Meldola, Forlì, Italy. E-mail: email@example.com.
Supported by the Italian Ministry of Health (Programma Straordinario di Ricerca Oncologica 2006).
The authors declare no conflicts of interest.
Received June 8, 2013
Accepted August 4, 2013