title: Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis.
abstract: OBJECTIVE
  Infection with human papillomavirus (HPV) type 16 has been suggested to be a risk factor for squamous cell carcinoma of the head and neck (SCCHN) and to be more commonly associated with SCCHN occurring in the oropharynx and in never-smokers. We hypothesized that HPV-16 exposure, as evidenced by seropositivity, is a risk factor for SCCHN and may be of particular importance in never-smokers.
  
  
  METHODS
  To test this hypothesis, we conducted a hospital-based case-control study of 120 patients with SCCHN (60 never-smokers and 60 matched smokers) and 120 cancer-free matched controls. We compared the presence of HPV-16 antibodies in ever-smoker and never-smoker patients matched on age (+/-5 years), sex, and tumor site. Each patient was also matched with a corresponding ever-smoker or never-smoker cancer-free control on age (+/-5 years) and sex. Serum was collected from study subjects and assayed for IgG reactivity to HPV-16 L1 virus-like particles by using an ELISA.
  
  
  RESULTS
  Forty-nine of the 120 case subjects (40.8%) but only 11 (9.2%) of the control subjects tested positive for HPV-16 antibodies (adjusted odds ratio, 6.69; 95% confidence interval, 3.01-14.90). Among cases, HPV-16 seropositivity was more common in those with oropharyngeal cancer (41 of 70, 58.6%) and poorly differentiated tumors (25 of 43, 58.1%). HPV-16 seropositivity was associated with a significantly increased risk of oropharyngeal cancer (adjusted odds ratio, 59.53; 95% confidence interval, 5.71-620.20). Whereas HPV-16 seropositivity was more common in never-smokers with SCCHN than in ever-smokers (43.3% versus 38.3%, respectively), this difference was not statistically significant.
  
  
  CONCLUSIONS
  HPV-16 infection is associated with a significant increased risk for oropharyngeal cancer but not oral cavity cancer. Furthermore, HPV-16 infection does not appear to be more common in never-smokers than ever-smokers with SCCHN.
authors.affiliation: Departments of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Kristina R
authors.initials: KR
authors.lastname: Dahlstrom
authors.forename: Karen
authors.initials: K
authors.lastname: Adler-Storthz
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Etzel
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Laura
authors.initials: L
authors.lastname: Dillon
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D002454:Cell Differentiation; D003367:Cotinine / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006258:Head and Neck Neoplasms / Q000821:virology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D009960:Oropharynx / Q000821:virology; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D012306:Risk; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D003367:Cotinine