title: Epstein-Barr virus in head and neck cancer assessed by quantitative polymerase chain reaction.
abstract: OBJECTIVE
  Epstein-Barr virus (EBV) has classically been associated with nasopharyngeal carcinoma and Burkitt's lymphoma. Recently, multiple studies have been published linking EBV with oral squamous cell carcinoma and, to a lesser extent, hypopharyngeal and laryngeal tumors. Using a sensitive method of detection, the authors sought to analyze the presence and quantity of EBV DNA in a large cohort of head and neck cancers.
  
  
  METHODS
  : Retrospective cohort study.
  
  
  METHODS
  Three hundred head and neck cancer samples exclusive of nasopharyngeal carcinoma were examined for the presence of EBV using quantitative polymerase chain reaction. Eighty-four tumor samples from the larynx, 30 from the hypopharynx, 73 from the oropharynx, and 113 from the oral cavity were analyzed for EBV quantity, which was expressed as the number of viral copies per cell genome. Representative samples, which contained the highest EBV DNA levels, were examined using in situ hybridization. Results were correlated with tumor grade and site and tobacco and alcohol exposure.
  
  
  RESULTS
  Three of 300 (1%) tumor samples were overtly positive for EBV DNA (defined as >0.1 copies of viral DNA/cell genome). Five of 300 (2%) tumor samples showed low levels (defined as >0.01 and <0.1 copies of viral DNA/cell genome), and 68 of 300 tumor samples (23%) showed trace levels (defined as < 0.01 copies of viral DNA/cell genome) of EBV DNA. No correlation was found between EBV positivity and tobacco exposure, alcohol exposure, or tumor grade.
  
  
  CONCLUSIONS
  In the overwhelming majority of head and neck cancers in this North American cohort, EBV did not appear to contribute to growth of a dominant clonal population with integrated EBV genome and was unlikely to be a genetic etiological agent in tumor development. The low quantities of EBV detected in a minority of head and neck cancers may be related to the presence of EBV genome in rare lymphoid or epithelial cells adjacent to the primary head and neck cancer.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: David
authors.initials: D
authors.lastname: Goldenberg
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Benoit
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Begum
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Koch
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology; D004279:DNA, Viral / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D016133:Polymerase Chain Reaction / Q000379:methods*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D004279:DNA, Viral