title: Biologic predictors of serologic responses to HPV in oropharyngeal cancer: The HOTSPOT study.
abstract: OBJECTIVE
  We hypothesized that viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer (HPVOPC).
  
  
  METHODS
  We conducted a multicenter study to measure HPV16-specific IgG among patients with HPVOPC, their long-term sexual partners, and healthy volunteers. Risk factor surveys and rinse and gargle specimens were collected. Peripheral blood samples at diagnosis were evaluated for IgG Abs to HPV16 antigens using a programmable ELISA assay. Predictors for HPV16 serologic responses were evaluated using univariate and multivariable linear regression.
  
  
  RESULTS
  116 patients with HPVOPC, 43 partners, and 81 healthy volunteers were enrolled and had baseline sera for analysis. Cases were primarily male (90%), with a median age of 56 years. Abs to E1, E2, E6 or E7 antigens were detected more often in HPVOPC compared with volunteers or partner sera (p<0.0001). HPV16 Abs to at least one early protein (E1, E2, E4, E5, E6, or E7) were detected in the sera of 90.6% of cases, 0% of partners and 7.4% of healthy volunteers. Gender, race, sexual behavior, and viral integration were not associated with antibody response. Younger age and higher oral HPV16 copy number were associated with higher HPV16 E6 and NE2 antibody levels.
  
  
  CONCLUSIONS
  HPV16 seroreactivity is commonly detected among patients with HPVOPC at diagnosis, but not among partners or healthy volunteers. Seroreactivity among cases are correlated with viral load and stage and not with other demographic or behavioral factors. Positive HPV16 serology was strongly associated with HPV 16 oropharyngeal cancer.
authors.affiliation: Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, United States. Electronic address: Dr.Karen@asu.edu.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Gerber
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, United States.
authors.forename: Sara I
authors.initials: SI
authors.lastname: Pai
authors.affiliation: Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, United States.
authors.forename: Julia N
authors.initials: JN
authors.lastname: Cheng
authors.affiliation: Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, United States.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Alam
authors.affiliation: Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, United States.
authors.forename: Sailaja
authors.initials: S
authors.lastname: Kesiraju
authors.affiliation: Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, United States; Simon A. Levin Mathematical, Computational and Modeling Sciences Center, Arizona State University, Tempe, AZ 85287, United States.
authors.forename: Diego
authors.initials: D
authors.lastname: Chowell
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Gross
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Haddad
authors.affiliation: Ohio State University, Comprehensive Cancer Center, Columbus, OH, United States.
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
authors.affiliation: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, United States.
authors.forename: Marshall
authors.initials: M
authors.lastname: Posner
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000821:virology*; D030361:Papillomavirus Infections / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D012747:Sexual Partners
chemical_list: D000914:Antibodies, Viral; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G
keywords: Antibodies; Biomarker; HPV; Oropharyngeal cancer; Serology