title: An evaluation of p16(INK4a) expression in cervical intraepithelial neoplasia specimens, including women with HIV-1.
abstract: Although several studies have evaluated the role of p16(INK4a) as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16(INK4a) in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16(INK4a) as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16(INK4a) was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16(INK4a) expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16(INK4a) in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16(INK4a) under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16(INK4a) expression in CIN 2-3.
authors.affiliation: Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. nicol@ioc.fiocruz.br
authors.forename: Alcina F
authors.initials: AF
authors.lastname: Nicol
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Golub
authors.forename: José R Lapa
authors.initials: JR
authors.lastname: e Silva
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Cunha
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Amaro-Filho
authors.forename: Nathalia S
authors.initials: NS
authors.lastname: Oliveira
authors.forename: Willker
authors.initials: W
authors.lastname: Menezes
authors.forename: Cecília Viana
authors.initials: CV
authors.lastname: Andrade
authors.forename: Fabio
authors.initials: F
authors.lastname: Russomano
authors.forename: Aparecida
authors.initials: A
authors.lastname: Tristão
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Ruth Khalili
authors.initials: RK
authors.lastname: Friedman
authors.forename: Marcia P
authors.initials: MP
authors.lastname: Oliveira
authors.forename: Andrea
authors.initials: A
authors.lastname: Pires
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications; D015497:HIV-1; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16