title: Unique DNA methylation signature in HPV-positive head and neck squamous cell carcinomas.
abstract: Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described, and the evidence of a functional impact on gene expression is still limited.
  
  
  
  We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours.
  
  
  
  We identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only five CpGs in a few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA sequencing in The Cancer Genome Atlas cohort.
  
  
  
  We identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs.
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France. davide.degli-esposti@irstea.fr.
authors.forename: Davide
authors.initials: D
authors.lastname: Degli Esposti
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Athena
authors.initials: A
authors.lastname: Sklias
authors.affiliation: Instituto Nacional de Cancer, Rio de Janeiro, Brazil.
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Lima
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), 06100, Nice, France.|Centre Antoine Lacassagne, Nice, 06189, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Beghelli-de la Forest Divonne
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cahais
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Fernandez-Jimenez
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Cros
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.|MTA-DE Public Health Research Group, University of Debrecen, Debrecen, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Ecsedi
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Cuenin
authors.affiliation: Environment Section, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Liacine
authors.initials: L
authors.lastname: Bouaoun
authors.affiliation: Environment Section, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Graham
authors.initials: G
authors.lastname: Byrnes
authors.affiliation: Infection Cancer Biology Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Rosita
authors.initials: R
authors.lastname: Accardi
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), 06100, Nice, France.|Centre Antoine Lacassagne, Nice, 06189, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sudaka
authors.affiliation: Université Côte d'Azur, Laboratoire de Virologie, CHU Nice-Archet, 06202, Nice, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Giordanengo
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
authors.forename: Hector
authors.initials: H
authors.lastname: Hernandez-Vargas
authors.affiliation: Instituto Nacional de Cancer, Rio de Janeiro, Brazil.
authors.forename: Luis Felipe Ribeiro
authors.initials: LF
authors.lastname: Pinto
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), 06100, Nice, France. Ellen.VAN-OBBERGHEN@unice.fr.|Centre Antoine Lacassagne, Nice, 06189, France. Ellen.VAN-OBBERGHEN@unice.fr.
authors.forename: Ellen
authors.initials: E
authors.lastname: Van Obberghen-Schilling
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France. HercegZ@iarc.fr.
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications*; D011401:Promoter Regions, Genetic; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
keywords: CpG shores; Differentially methylated regions; HPV; Head and neck squamous cell carcinomas; Predictive models