title: Prognostic value of p16-INK4A protein in women with negative or CIN1 histology result: a follow-up study.
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.
authors.affiliation: Lega Italiana per la Lotta ai Tumori, Provincial Section of Latina, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pacchiarotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrari
authors.forename: Paola
authors.initials: P
authors.lastname: Bellardini
authors.forename: Francesco
authors.initials: F
authors.lastname: Chini
authors.forename: Guido
authors.initials: G
authors.lastname: Collina
authors.forename: Paolo
authors.initials: P
authors.lastname: Dalla Palma
authors.forename: Bruno
authors.initials: B
authors.lastname: Ghiringhello
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Maccallini
authors.forename: Fabio
authors.initials: F
authors.lastname: Musolino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Negri
authors.forename: Roberto
authors.initials: R
authors.lastname: Pisa
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sabatucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Giorgi Rossi
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D003127:Colposcopy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D011379:Prognosis; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: cervical cancer; cervical intraepithelial neoplasia; cohort study; colposcopy; p16; prognostic value; screening