title: HPV Serum Antibodies as Predictors of Survival and Disease Progression in Patients with HPV-Positive Squamous Cell Carcinoma of the Oropharynx.
abstract: OBJECTIVE
  Oropharyngeal carcinoma positive for human papillomavirus type 16 (HPV16) has a significantly better prognosis than oropharyngeal carcinoma unrelated to HPV. Within HPV16-positive oropharyngeal carcinoma, biomarkers of prognosis are urgently needed to individualize care. We hypothesized that serum antibodies specific to HPV16, the major HPV type causing oropharyngeal carcinoma, have biologic relevance and are potential biomarkers for improved prognosis among patients with HPV16-positive oropharyngeal carcinoma.
  
  
  METHODS
  IgG antibodies to the HPV16 antigens E1, E4-E7, L1, L2, and the N-terminal and C-terminal fragments of E2 (NE2, CE2) were quantified using a custom programmable enzyme-linked immunosorbent assay. Sera were obtained at diagnosis from 209 oropharyngeal carcinoma patients (96 HPV16-positive). The ratios of median fluorescent intensity (MFI) for each antigen to MFI for control GST protein were determined. Kaplan-Meier survival curves and Cox proportional hazards regression were used to determine survival differences between groups. ROC curves were used to determine the best combination of E antibodies to predict disease recurrence.
  
  
  RESULTS
  E1, NE2, and E6 antibody positivity were all strongly associated with improved overall and progression-free survival in the entire cohort and in patients with known HPV16-positive tumors (P < 0.05). For both overall and progression-free survival among HPV-positive patients, hazard ratios were 0.2 for NE2, 0.3 for E1, and 0.3 for E6 antibody positivity.
  
  
  CONCLUSIONS
  We identified three HPV16-specific antibodies that are associated with improved overall and progression-free survival in patients with HPV-related oropharyngeal carcinoma. These results suggest that differential serologic responses in patients may reflect differential biologic processes within the host and tumor and may have prognostic value.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kristina R
authors.initials: KR
authors.lastname: Dahlstrom
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, Arizona.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, Arizona.
authors.forename: Julia N
authors.initials: JN
authors.lastname: Cheng
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, Arizona. Simon A. Levin Mathematical, Computational, and Modeling Sciences Center, Arizona State University, Tempe, Arizona.
authors.forename: Diego
authors.initials: D
authors.lastname: Chowell
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.affiliation: Tisch Cancer Institute, Icahn School of Medicine at Mt. Sinai, New York City, New York.
authors.forename: Marshall
authors.initials: M
authors.lastname: Posner
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. esturgis@mdanderson.org.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
mesh_terms: D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000401:mortality* / Q000473:pathology; D004279:DNA, Viral; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000209:etiology* / Q000401:mortality* / Q000473:pathology; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral