title: Human papillomavirus infections and upper aero-digestive tract cancers: the ARCAGE study.
abstract: BACKGROUND
  Human papillomavirus (HPV) is causally implicated in a subset of cancers of the upper aero-digestive tract (UADT).
  
  
  METHODS
  Associations between type-specific HPV antibodies were examined among 1496 UADT cancer case subjects and 1425 control subjects by estimating odds ratios (ORs) in logistic regression analyses adjusted for potential confounders. The agreement between serology and tumor markers of HPV infection, including presence of HPV DNA and p16 expression, were examined in a subset of tumors.
  
  
  RESULTS
  HPV16 L1 seropositivity was associated with increased risk of oral cavity and oropharyngeal cancer (OR = 1.94, 95% confidence interval [CI] = 1.03 to 3.65; OR = 8.60, 95% CI = 5.21 to 14.20, respectively). HPV16 E6 antibodies were present in 30.2% of oropharyngeal case subjects and only 0.8% of control subjects (OR = 132.0, 95% CI = 65.29 to 266.86). Combined seropositivity to HPV16 E6 and E7 was rare (n = 1 of 1425 control subjects). An agreement of 67% was observed between HPV16 E6 serology and the corresponding presence of an HPV-related cancer: four of six HPV DNA-positive/p16-overexpressing tumors were HPV16 E6 antibody positive. An HPV16 independent association was observed for HPV18 and oropharyngeal cancer (OR = 8.14, 95% CI = 2.21 to 29.99 for HPV18 E6 seropositivity) and HPV6 and laryngeal cancer (OR = 3.25, 95% CI = 1.46 to 7.24 for HPV6 E7 seropositivity).
  
  
  CONCLUSIONS
  These results confirm an important role for HPV16 infection in oropharyngeal cancer. HPV16 E6 antibodies are strongly associated with HPV16-related oropharyngeal cancers. Continuing efforts are needed to consider both HPV serology and p16 staining as biomarkers relevant to the etiology and natural history of HPV16-related oropharyngeal tumors. These results also support a marginal role for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer.
authors.affiliation: Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Devasena
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authors.lastname: Anantharaman
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.forename: Behnoush
authors.initials: B
authors.lastname: Abedi-Ardekani
authors.forename: Christine
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authors.lastname: Carreira
authors.forename: Sandrine
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authors.lastname: McKay-Chopin
authors.forename: Valerie
authors.initials: V
authors.lastname: Gaborieau
authors.forename: Manuela
authors.initials: M
authors.lastname: Marron
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ahrens
authors.forename: Ivana
authors.initials: I
authors.lastname: Holcátová
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.forename: Kristina
authors.initials: K
authors.lastname: Kjaerheim
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Simonato
authors.forename: Xavier
authors.initials: X
authors.lastname: Castellsague
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Macfarlane
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Biggs
authors.forename: Nalin
authors.initials: N
authors.lastname: Thakker
authors.forename: Ariana
authors.initials: A
authors.lastname: Znaor
authors.forename: Peter
authors.initials: P
authors.lastname: Thomson
authors.forename: Cristina
authors.initials: C
authors.lastname: Canova
authors.forename: David I
authors.initials: DI
authors.lastname: Conway
authors.forename: Claire M
authors.initials: CM
authors.lastname: Healy
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D000368:Aged; D000914:Antibodies, Viral / Q000302:isolation & purification*; D014408:Biomarkers, Tumor / Q000276:immunology; D016022:Case-Control Studies; D004279:DNA, Viral / Q000302:isolation & purification*; D005260:Female; D005455:Fluorescent Antibody Technique; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000821:virology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D012097:Repressor Proteins / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D000914:Antibodies, Viral; D014408:Biomarkers, Tumor; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16