title: Oral cavity tumors in younger patients show a poor prognosis and do not contain viral RNA.
abstract: BACKGROUND
  Oral cavity and in particular oral tongue cancers occur with a rising incidence in younger patients often lacking the typical risk factors of tobacco use, alcohol use, and human papilloma virus (HPV) infection. Their prognosis when treated with chemoradiation has not been well studied and responsible risk factors remain elusive. A viral etiology (other than HPV) has been hypothesized.
  
  
  METHODS
  First we analyzed outcomes from 748 head and neck cancer patients with locoregionally advanced stage tumors treated with curative-intent chemoradiation by anatomic site. Second, we analyzed seven oral tongue (OT) tumors from young, non-smokers/non-drinkers for the presence of viral mRNA using short-read massively-parallel sequencing (RNA-Seq) in combination with a newly-developed digital subtraction method followed by viral screening and discovery algorithms. For positive controls we used an HPV16-positive HNC cell line, a cervical cancer, and an EBV-LMP2A transgene lymphoma.
  
  
  RESULTS
  Younger patients with oral cavity tumors had worse outcomes compared to non-oral cavity patients. Surprisingly none of the seven oral tongue cancers showed significant presence of viral transcripts. In positive controls the expected viral material was identified.
  
  
  CONCLUSIONS
  Oral cavity tumors in younger patients have a poor prognosis and do not appear to be caused by a transcriptionally active oncovirus.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: J
authors.initials: J
authors.lastname: Brägelmann
authors.forename: I
authors.initials: I
authors.lastname: Dagogo-Jack
authors.forename: M
authors.initials: M
authors.lastname: El Dinali
authors.forename: T
authors.initials: T
authors.lastname: Stricker
authors.forename: C D
authors.initials: CD
authors.lastname: Brown
authors.forename: Z
authors.initials: Z
authors.lastname: Zuo
authors.forename: A
authors.initials: A
authors.lastname: Khattri
authors.forename: M
authors.initials: M
authors.lastname: Keck
authors.forename: M E
authors.initials: ME
authors.lastname: McNerney
authors.forename: R
authors.initials: R
authors.lastname: Longnecker
authors.forename: K
authors.initials: K
authors.lastname: Bieging
authors.forename: M
authors.initials: M
authors.lastname: Kocherginsky
authors.forename: K
authors.initials: K
authors.lastname: Alexander
authors.forename: R
authors.initials: R
authors.lastname: Salgia
authors.forename: M W
authors.initials: MW
authors.lastname: Lingen
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
authors.forename: K P
authors.initials: KP
authors.lastname: White
authors.forename: E E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: T Y
authors.initials: TY
authors.lastname: Seiwert
mesh_terms: D000328:Adult; D000465:Algorithms; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000473:pathology* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis*; D016019:Survival Analysis
chemical_list: D012367:RNA, Viral