title: Follow-up study of patients with cervical intraepithelial neoplasia grade 1 overexpressing p16Ink4a.
abstract: OBJECTIVE
  The p16 (p16(Ink4a)) 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.
authors.affiliation: *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.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cortecchia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Galanti
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sgadari
authors.forename: Silvano
authors.initials: S
authors.lastname: Costa
authors.forename: Margherita
authors.initials: M
authors.lastname: De Lillo
authors.forename: Licia
authors.initials: L
authors.lastname: Caprara
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barillari
authors.forename: Paolo
authors.initials: P
authors.lastname: Monini
authors.forename: Roberto
authors.initials: R
authors.lastname: Nannini
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.forename: Lauro
authors.initials: L
authors.lastname: Bucchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology