title: Serum Antibodies to HPV16 Early Proteins Warrant Investigation as Potential Biomarkers for Risk Stratification and Recurrence of HPV-Associated Oropharyngeal Cancer.
abstract: Human papillomavirus (HPV) is responsible for increasing incidence of oropharyngeal cancer. At present, there are no biomarkers in the surveillance algorithm for HPV-positive oropharyngeal cancer (HPV-OPC). HPV16 E6 antibody precedes oropharyngeal cancer diagnosis. If HPV16 E6 indeed precedes primary diagnosis, it is similarly expected to precede disease recurrence and may have a potential role as a biomarker for surveillance of HPV-OPC. To determine whether HPV antibody titers have a potential role as early markers of disease recurrence or prognosis, a retrospective pilot study was designed to determine whether HPV16 early antibody titers E6, E7, E1, and E2 decrease after treatment of HPV16-positive OPC. Trends in pretreatment, early (≤6 months after treatment), and late posttreatment (>6 months after treatment) HPV16 antibody titers were examined. There were 43, 34, and 52 subjects with serum samples available for pretreatment, early, and late posttreatment intervals. Mean pretreatment antibody levels were higher than posttreatment antibody levels. Average antibody levels decreased significantly over time for E6 (Ptrend = 0.001) and E7 (Ptrend < 0.001). Six disease recurrences were observed during the follow-up period (median, 4.4 years). In univariate analysis, a log-unit increase in pretreatment E6 titer was significantly associated with increased risk of disease recurrence (HR, 5.42; 95% CI, 1.1-25.7; P = 0.03). Therefore, levels of antibodies to HPV16 early oncoproteins decline after therapy. Higher E6 titers at diagnosis are associated with significant increases in the risk of recurrence. These data support the prospective evaluation of HPV16 antibodies as markers of surveillance and for risk stratification at diagnosis.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. cfakhry1@jhmi.edu.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Qualliotine
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Daria A
authors.initials: DA
authors.lastname: Gaykalova
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Rathan M
authors.initials: RM
authors.lastname: Subramaniam
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Koch
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: David W
authors.initials: DW
authors.lastname: Eisele
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Joseph
authors.initials: J
authors.lastname: Califano
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Raphael P
authors.initials: RP
authors.lastname: Viscidi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000473:pathology* / Q000821:virology; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D009959:Oropharyngeal Neoplasms / Q000097:blood / Q000473:pathology* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000097:blood / Q000473:pathology* / Q000821:virology; D011379:Prognosis; D012097:Repressor Proteins / Q000276:immunology*; D012189:Retrospective Studies
chemical_list: D000914:Antibodies, Viral; D014408:Biomarkers, Tumor; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins