title: Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer.
abstract: OBJECTIVE
  Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.
  
  
  METHODS
  We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.
  
  
  RESULTS
  HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.
  
  
  CONCLUSIONS
  HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.
authors.affiliation: National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
authors.forename: Aimée R
authors.initials: AR
authors.lastname: Kreimer
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Dagmar
authors.initials: D
authors.lastname: Drogen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Kim
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authors.lastname: Overvad
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrañaga
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick
authors.initials: N
authors.lastname: Wareham
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Sara
authors.initials: S
authors.lastname: Grioni
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Göran
authors.initials: G
authors.lastname: Laurell
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.forename: Johanna
authors.initials: J
authors.lastname: Ekström
authors.forename: Guri
authors.initials: G
authors.lastname: Skeie
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.forename: Graham
authors.initials: G
authors.lastname: Byrnes
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000032:analysis* / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000276:immunology / Q000821:virology*; D052162:Human papillomavirus 16 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000276:immunology / Q000821:virology; D012097:Repressor Proteins / Q000276:immunology; D014481:United States / Q000453:epidemiology
chemical_list: D000914:Antibodies, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins