title: Human papillomavirus, Epstein-Barr virus, and methylation status of p16ink4ain penile cancer.
abstract: Little is known about penile carcinogenesis. The aim of this study was to evaluate the prevalence of HPV and EBV, and the methylation status of p16ink4ain penile cancer samples, and to contribute to the understanding of the mechanisms responsible for penile cancer development. HPV DNA was detected in 63.6% of 122 cases, with HPV16 being the most prevalent type. EBV DNA was detected in 47.7%, with EBV-1 being the most prevalent type. HPV/EBV co-infections were found in 27.3% of the cases. Hypermethylation in p16ink4awas detected in 64.5% of 110 tested cases. An association between the absence of HPV absence and p16ink4ahypermethylation was also found. Death and/or progressive disease was associated with grade (P = 0.001), T stage (P < 0.0001), and N stage (P < 0.0001). In the multivariable model, grade and N stage were independent risk factors for disease-free survival (P = 0.008 and P < 0.001, respectively). Patients without viral infection had a median age significantly lower than that of the HPV-infected patients. We suggest at least two pathways for penile carcinogenesis, one HPV-independent linked to epigenetic events, probably via p16ink4ainactivation; and another, dependent on HPV infection.
authors.affiliation: From the Department of Microbiology and Parasitology Biomedical Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Larissa Alves
authors.initials: LA
authors.lastname: Afonso
authors.affiliation: From the Department of Microbiology and Parasitology Biomedical Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Fernanda Nahoum
authors.initials: FN
authors.lastname: Carestiato
authors.affiliation: Departments of Urology, Brazilian National Cancer Institute and Hospital Mário Kröeff, Rio de Janeiro, Brazil.
authors.forename: Antonio Augusto
authors.identifier: 0000-0002-6497-511X
authors.initials: AA
authors.lastname: Ornellas
authors.affiliation: Circulating Biomarkers Laboratory, Department of Pathology, Rio de Janeiro, Brazil.|Programa de Pós-Graduação em Ciências Médicas (PGCM), Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Ornellas
authors.affiliation: From the Department of Microbiology and Parasitology Biomedical Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Willker Menezes
authors.initials: WM
authors.lastname: Rocha
authors.affiliation: From the Department of Microbiology and Parasitology Biomedical Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Thaissa Isaias
authors.initials: TI
authors.lastname: Cordeiro
authors.affiliation: From the Department of Microbiology and Parasitology Biomedical Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Daniela Ceperuelo
authors.initials: DC
authors.lastname: Lisboa
authors.affiliation: Circulating Biomarkers Laboratory, Department of Pathology, Rio de Janeiro, Brazil.|Research Coordination, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
authors.forename: Gilda Brown
authors.initials: GB
authors.lastname: Alves
authors.affiliation: From the Department of Microbiology and Parasitology Biomedical Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: Silvia Maria Baeta
authors.initials: SMB
authors.lastname: Cavalcanti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D060085:Coinfection / Q000453:epidemiology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology / Q000503:physiopathology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000503:physiopathology; D010412:Penile Neoplasms / Q000235:genetics / Q000401:mortality / Q000503:physiopathology / Q000821:virology*; D015995:Prevalence; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: EBV; HPV; MSP-PCR; epigenetics; p16ink4a hypermethylation