title: Associations of Oral α-, β-, and γ-Human Papillomavirus Types With Risk of Incident Head and Neck Cancer.
abstract: OBJECTIVE
  Prospective studies are needed to examine the temporal relationship between oral human papillomavirus (HPV) detection and risk of head and neck squamous cell carcinoma (HNSCC). Moreover, the oral cavity contains a wide spectrum of α-, β-, and γ-HPV types, but their association with risk of HNSCC is unknown.
  
  
  OBJECTIVE
  To prospectively examine associations between α-, β-, and γ-HPV detection in the oral cavity and incident HNSCC.
  
  
  METHODS
  A nested case-control study was carried out among 96 650 participants, cancer free at baseline, with available mouthwash samples in 2 prospective cohort studies: (1) the American Cancer Society Cancer Prevention Study II Nutrition Cohort and (2) the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident cases of HNSCC (n = 132) were identified during an average 3.9 years of follow-up in both cohorts. Three controls per case (n = 396) were selected through incidence density sampling and matched on age, sex, race/ethnicity, and time since mouthwash collection.
  
  
  METHODS
  Through a next-generation sequencing assay, DNA from α-, β-, and γ-HPV types were detected. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs, adjusting for smoking history, alcohol consumption, and detection of HPV-16 for β- and γ-HPVs.
  
  
  METHODS
  Incident HNSCC, which includes cancers of the oropharynx, oral cavity, and larynx.
  
  
  RESULTS
  A total of 132 participants developed HNSCC during the follow-up period (103 men and 29 women; average age at baseline, 66.5 years). Oral HPV-16 detection was associated with incident HNSCC (OR, 7.1; 95% CI, 2.2-22.6), with positive association for oropharyngeal SCC (OR, 22.4; 95% CI, 1.8-276.7), but not for oral cavity (OR, 4.5; 95% CI, 0.6-34.7) or laryngeal SCCs (OR, 0.11; 95% CI, 0.01-834.80). Detection of β1-HPV-5 and β2-HPV-38 types, as well as γ-11 and γ-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P < .01 for all comparisons). Detection of β1-HPV-5 type was associated with oropharyngeal (OR, 7.42; 95% CI, 0.98-56.82; P = .054), oral cavity (OR, 5.34; 95% CI, 1.51-18.80; P = .01), and laryngeal SCCs (OR, 2.71; 95% CI, 1.00-7.43; P = .05), whereas γ11- and γ12-HPV species were associated with both oral cavity (OR, 7.47; 95% CI, 1.21-46.17; P = .03; and OR, 6.71; 95% CI, 1.47-30.75; P = .01, respectively) and laryngeal SCCs (OR, 7.49; 95% CI, 1.10-51.04; P = .04 and OR, 5.31; 95% CI, 1.13-24.95; P = .03, respectively).
  
  
  CONCLUSIONS
  This study demonstrates that HPV-16 detection precedes the incidence of oropharyngeal SCC. Associations of other HPVs, including γ11- and γ12-HPV species and β1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Ilir
authors.initials: I
authors.lastname: Agalliu
authors.affiliation: American Cancer Society, Atlanta, Georgia.
authors.forename: Susan
authors.initials: S
authors.lastname: Gapstur
authors.affiliation: Department of Pediatrics (Genetics), Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Zigui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: American Cancer Society, Atlanta, Georgia.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Anderson
authors.affiliation: American Cancer Society, Atlanta, Georgia.
authors.forename: Lauren
authors.initials: L
authors.lastname: Teras
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Aimée R
authors.initials: AR
authors.lastname: Kreimer
authors.affiliation: Department of Population Health and Environmental Medicine, New York University, New York.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York3Department of Pediatrics (Genetics), Albert Einstein College of Medicine, Bronx, New York6Departments of Microbiology and Immunology and Obstetrics, Gyn.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk