title: Immune Response to HPV16 E6 and E7 Proteins and Patient Outcomes in Head and Neck Cancer.
abstract: OBJECTIVE
  Pathology-based measures of human papillomavirus (HPV) status are routinely obtained in the care of head and neck cancer and are clearly associated with patient outcome for cancers of the oropharynx. However, it is unclear if HPV status is of high value for cancers of the larynx and oral cavity. In addition, it is possible to assess HPV infection using serology-based methods; however, the suitability of this pathology-independent measure for predicting patient outcome in head and neck cancer is unknown.
  
  
  OBJECTIVE
  To investigate whether immunologic response to HPV16 is associated with patient survival across anatomic sites, independent of smoking and drinking history.
  
  
  METHODS
  This was a population-based study of 1054 patients with head and neck cancer in the greater Boston, Massachusetts, area (1999-2003, 2006-2011).
  
  
  METHODS
  All-cause survival in relation to HPV16 E6 and E7 seropositivity.
  
  
  RESULTS
  The 1054 patients reflected the demographics of those treated in this timeframe (75% male; mean age, 59 years). Seropositivity was very strongly associated with improved survival overall (hazard ratio HR], 0.33; 95% CI, 0.24-0.45; P < .001), with no evidence that the magnitude of immune response, as assessed by titer levels, effected outcome. Seropositivity was associated with improved patient survival across all head and neck cancer sites: HR for oropharynx cancer, 0.26; 95% CI, 0.18-0.39; for oral cavity cancer, 0.45; 95% CI, 0.18-0.80; and for larynx cancer, 0.29; 95% CI, 0.10-0.85. In addition, the associations with seropositivity were similar across smoking and/or drinking exposure groups: HRfor low exposure, 0.52; 95% CI, 0.20-1.36; for moderate exposure, 0.42; 95% CI, 0.25-0.70; for heavy exposure, 0.51; 95% CI, 0.36-0.73. In a subset of 162 patients with both HPV serology and p16 immunohistochemical (IHC) measures available, both measures were similarly associated with survival in the oropharynx (HR for serology, 0.16; 95% CI, 0.03-0.47; for p16 measures, 0.16; 95% CI, 0.03-0.46), whereas only serology was associated with outcome when considering all head and neck cancer cases (HR for serology,0.49; 95% CI, 0.23-1.04; for p16, 0.65; 95% CI, 0.30-1.42).
  
  
  CONCLUSIONS
  Collectively, these data suggest that a positive serologic response to HPV16 oncoproteins may be the best approach to assess HPV-disease for clinical outcome because it is associated with survival for all types of disease and is a marker that is not dependent on pathology material.
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis2Division of Epidemiology and Community Health, University of Minnesota, Minneapolis.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Nelson
authors.affiliation: Research Program Infection and Cancer, German Cancer Research Center, DKFZ, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Michaud
authors.affiliation: Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: McClean
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Langevin
authors.affiliation: Department of Epidemiology, Brown University, Providence, Rhode Island.
authors.forename: Melissa N
authors.initials: MN
authors.lastname: Eliot
authors.affiliation: Department of Epidemiology, Brown University, Providence, Rhode Island8Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey