title: A predictive transcriptomic signature of oropharyngeal cancer according to HPV16 status exclusively.
abstract: OBJECTIVE
  Human-papillomaviruses (HPV) type 16 is a causative agent in an increasing subset of oropharyngeal squamous cell carcinomas (OPSCCs). These tumors have distinct oncogenic mechanisms and a more favorable prognosis than tobacco-induced OPSCCs. Although these differences emphasize the need for a specific therapeutic approach, HPV status is still not used to guide treatment. A better characterization of the molecular profile related to HPV16-induced OPSCC might help to develop personalized treatments.
  
  
  METHODS
  Using a human whole-genome DNA-microarray, we have examined the gene expression profiles in 15 HPV-negative and 15 transcriptionally-active HPV-positive OPSCCs. The study was conducted in two steps. Firstly, a learning/training-set consisting of 8 HPV16-positive and 8 HPV16-negative OPSCCs was analyzed to identify a specific signature. Potentially confounding factors (stage, sex and tobacco) were equally distributed in both groups. Subsequently the robustness of this signature was confirmed by blind case-by-case classification of a validation-set composed of the 14 remaining tumors.
  
  
  RESULTS
  We have identified a signature composed of 224 genes, which discriminates HPV16-induced OPSCC from their HPV-negative counterparts. After the blind classification of the 14 tumours, the viral status was revealed: 13 out of 14 tumors were correctly classified according to tumor etiology, 1/14 was not determined and none were misclassified. Several of the differentially expressed genes were involved in cell-cycle regulation, DNA replication and repair, transcription regulation, immune response and apoptosis.
  
  
  CONCLUSIONS
  Our study contributes to a better understanding of pathogenic mechanisms involved in the development of HPV-positive OPSCCs and in the identification of potential therapeutic targets.
authors.affiliation: ER2 unit and GRC10, Université Pierre et Marie Curie, Paris, France; Department of Head and Neck Surgery, Institut de Cancérologie Gustave Roussy, Villejuif, France. Electronic address: haitham.mirghani@gustaveroussy.fr.
authors.forename: Haitham
authors.initials: H
authors.lastname: Mirghani
authors.affiliation: CEA, DSV, iRCM, Laboratory of Experimental Cancerology, BP64, 92265 Fontenay-aux-Roses Cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ugolin
authors.affiliation: CEA, DSV, iRCM, Laboratory of Experimental Cancerology, BP64, 92265 Fontenay-aux-Roses Cedex, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ory
authors.affiliation: Department of Pathology, GHUEP, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Lefèvre
authors.affiliation: PartnerChip, Bat. G2, Genopole Campus 2, Evry, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baulande
authors.affiliation: Laboratory of Clinical and Experimental Pathology and Biobank of CHUN, Pasteur Hospital, Nice F-06001, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.affiliation: ER2 unit and GRC10, Université Pierre et Marie Curie, Paris, France; Department of Otolaryngology-Head and Neck Surgery, GHUEP, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Jean Lacau
authors.initials: JL
authors.lastname: St Guily
authors.affiliation: CEA, DSV, iRCM, Laboratory of Experimental Cancerology, BP64, 92265 Fontenay-aux-Roses Cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevillard
authors.affiliation: ER2 unit and GRC10, Université Pierre et Marie Curie, Paris, France; Tumours Genomic Unit, GHUEP, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Lacave
mesh_terms: D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000821:virology; D059467:Transcriptome
keywords: DNA-microarray; Gene expression profile; Human papillomavirus 16; Oropharyngeal/oropharynx cancer; p16