title: Serum antibodies to the HPV16 proteome as biomarkers for head and neck cancer.
abstract: BACKGROUND
  Human papillomavirus (HPV) type 16 is associated with oropharyngeal carcinomas (OPC). Antibodies (Abs) to HPV16 E6 and E7 oncoproteins have been detected in patient sera; however, Abs to other early HPV-derived proteins have not been well explored.
  
  
  METHODS
  Antibodies to the HPV16 proteome were quantified using a novel multiplexed bead assay, using C-terminal GST-fusion proteins captured onto Luminex beads. Sera were obtained from untreated patients with OPC (N=40), partners of patients with HPV16+ OPC (N=11), and healthy controls (N=50).
  
  
  RESULTS
  Oropharyngeal carcinomas patients with known virus-like capsid particle+ Abs had elevated serum Abs to HPV16 E1, E2, E4, E6, and E7, and L1 antibody levels, but not E5. The ratios of specific median fluorescence intensity to p21-GST compared with controls were E1: 50.7 vs 2.1; E4: 14.6 vs 1.3; E6: 11.3 vs 2.4; E7: 43.1 vs 2.6; and L1: 10.3 vs 2.6 (each P≤0.01). In a validation cohort, HPV16 E1, E2, and E7 antibody levels were significantly elevated compared with healthy control samples (P≤0.02) and partners of OPC patients (P≤0.01).
  
  
  CONCLUSIONS
  Patients with HPV16+ OPC have detectable Abs to E1, E2, and E7 proteins, which are potential biomarkers for HPV-associated OPC.
authors.affiliation: Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA 02115, USA. kanderson@partners.org
authors.forename: K S
authors.initials: KS
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: G
authors.initials: G
authors.lastname: D'Souza
authors.forename: A B
authors.initials: AB
authors.lastname: Riemer
authors.forename: J
authors.initials: J
authors.lastname: Lorch
authors.forename: R
authors.initials: R
authors.lastname: Haddad
authors.forename: S I
authors.initials: SI
authors.lastname: Pai
authors.forename: J
authors.initials: J
authors.lastname: Longtine
authors.forename: M
authors.initials: M
authors.lastname: McClean
authors.forename: J
authors.initials: J
authors.lastname: LaBaer
authors.forename: K T
authors.initials: KT
authors.lastname: Kelsey
authors.forename: M
authors.initials: M
authors.lastname: Posner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis / Q000821:virology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D020543:Proteome / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014408:Biomarkers, Tumor; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D020543:Proteome; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16