title: HPV16 antibodies as risk factors for oropharyngeal cancer and their association with tumor HPV and smoking status.
abstract: BACKGROUND
  Antibodies (Abs) to the HPV16 proteome increase risk for HPV-associated OPC (HPVOPC). The goal of this study was to investigate the association of a panel of HPV16 Abs with risk for OPC as well as the association of these Abs with tumor HPV and smoking status among patients with OPC.
  
  
  METHODS
  IgG Abs to the HPV16 antigens E1, E2, E4, E5, E6, E7, L1, L2 were quantified using a programmable ELISA assay. Sera were obtained from 258 OPC patients at diagnosis and 250 healthy controls. HPV16 tumor status was measured by PCR for 137 cases. Multivariable logistic regression was used to calculate odds ratios for the association of HPV16 Abs with risk for OPC.
  
  
  RESULTS
  HPV16 E1, E2, E4, E5, E6, E7 and L1-specific IgG levels were elevated in OPC patients compared to healthy controls (p<0.05). After multivariable adjustment, Ab positivity for NE2, CE2, E6, and/or E7 was associated with OPC risk (OR [95% CI], 249.1 [99.3-624.9]). Among patients with OPC, Ab positivity for these antigens was associated with tumor HPV status, especially among never or light smokers (OR [95% CI], 6.5 [2.1-20.1] and OR [95% CI], 17.5 [4.0-77.2], respectively).
  
  
  CONCLUSIONS
  Antibodies to HPV16 proteins are associated with increased risk for HPVOPC. Among patients with OPC, HPV16 Abs are associated with tumor HPV status, in particular among HPV positive patients with no or little smoking history.
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, United States. Electronic address: Karen.Anderson.1@asu.edu.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.affiliation: Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Kristina R
authors.initials: KR
authors.lastname: Dahlstrom
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, United States.
authors.forename: Julia N
authors.initials: JN
authors.lastname: Cheng
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, United States.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Alam
authors.affiliation: Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Gross
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, United States; Simon A. Levin Mathematical, Computational, and Modeling Sciences Center, Arizona State University, Tempe, AZ, United States.
authors.forename: Diego
authors.initials: D
authors.lastname: Chowell
authors.affiliation: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, United States.
authors.forename: Marshall
authors.initials: M
authors.lastname: Posner
authors.affiliation: Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
mesh_terms: D000368:Aged; D000914:Antibodies, Viral / Q000235:genetics*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000821:virology; D012307:Risk Factors; D012907:Smoking / Q000473:pathology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G
keywords: Antibodies; Biomarker; HPV; Head and neck cancer; Oropharyngeal cancer; Serology