title: Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment.
abstract: Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk.
  
  
  
  115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16.
  
  
  
  At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p=0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR]=1.81, 95%CI=0.47-6.92).
  
  
  
  This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Yuehan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Haddad
authors.affiliation: Department of Otolaryngology, Icahn School of Medicine at Mount Sinai Medical Center, 1 Gustave L. Levy Pl, New York, NY 10029, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Miles
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Wentz
authors.affiliation: Division of Surgery, Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Gross
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
authors.affiliation: Department of Radiation Oncology, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Quon
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Lorch
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Gourin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OH 97239, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Clayburgh
authors.affiliation: Tisch Cancer Institute, Head and Neck Oncology Center, Icahn School of Medicine at Mount Sinai Medical Center, 1 Gustave L. Levy Pl, New York, NY 10029, USA.
authors.forename: Krzysztof J
authors.initials: KJ
authors.lastname: Misiukiewicz
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Richmon
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OH 97239, USA.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Andersen
authors.affiliation: Tisch Cancer Institute, Head and Neck Oncology Center, Icahn School of Medicine at Mount Sinai Medical Center, 1 Gustave L. Levy Pl, New York, NY 10029, USA.
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Posner
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: gdsouza2@jhu.edu.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
mesh_terms: D052685:Alphapapillomavirus / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000821:virology
chemical_list: D000914:Antibodies, Viral
keywords: Antibodies; E6; HPV; OPSCC; Seroprevalence