title: Prognostic Implication of Persistent Human Papillomavirus Type 16 DNA Detection in Oral Rinses for Human Papillomavirus-Related Oropharyngeal Carcinoma.
abstract: OBJECTIVE
  Human papillomavirus-related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear.
  
  
  OBJECTIVE
  To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival.
  
  
  METHODS
  Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study.
  
  
  METHODS
  Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis.
  
  
  RESULTS
  Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months.
  
  
  CONCLUSIONS
  Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Eleni M
authors.initials: EM
authors.lastname: Rettig
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Alicia
authors.initials: A
authors.lastname: Wentz
authors.affiliation: Tisch Cancer Institute, Head and Neck Oncology Center, Icahn School of Medicine at Mount Sinai Medical Center, New York, New York.
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Posner
authors.affiliation: Division of Surgery, Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Gross
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Haddad
authors.affiliation: Viral Oncology Program, Ohio State University Comprehensive Cancer Center, Columbus.
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
authors.affiliation: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Harry
authors.initials: H
authors.lastname: Quon
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, Texas.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Sikora
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon.
authors.forename: William J
authors.initials: WJ
authors.lastname: Stott
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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, Baltimore, Maryland.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Gourin
authors.affiliation: Viral Oncology Program, Ohio State University Comprehensive Cancer Center, Columbus.
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Viral Oncology Program, Ohio State University Comprehensive Cancer Center, Columbus.
authors.forename: Weihong
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Otolaryngology, Icahn School of Medicine at Mount Sinai Medical Center, New York, New York.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Miles
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Richmon
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon.
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, New York, New York.
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, Baltimore, Maryland11Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Gerber
authors.affiliation: Louisiana State University School of Medicine, New Orleans.
authors.forename: Shirani D
authors.initials: SD
authors.lastname: Rajan
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
mesh_terms: D002277:Carcinoma / Q000453:epidemiology / Q000473:pathology / Q000628:therapy / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D018450:Disease Progression; D018572:Disease-Free Survival; D061809:Human Papillomavirus DNA Tests; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000821:virology*; D009364:Neoplasm Recurrence, Local; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy / Q000821:virology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D062606:Tertiary Care Centers; D007507:Therapeutic Irrigation; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D004279:DNA, Viral