title: Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer.
abstract: BACKGROUND
  Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited.
  
  
  METHODS
  A retrospective analysis of patients with recurrent OPSCC from 2 institutions between 2000 and 2012 was performed. p16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival (OS) was examined using Kaplan-Meier and Cox proportional hazards methods.
  
  
  RESULTS
  The current study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority of patients were HPV-positive (80 patients). HPV-positive tumor status was associated with longer time to disease recurrence (P<.01). Anatomic site distribution of disease recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR], 0.23; 95% confidence interval [95% CI], 0.09-0.58 [P = .002]), longer time to disease recurrence (≥ 1 year; aHR, 0.36; 95% CI, 0.18-0.74 [P = .006]), and surgical salvage (aHR, 0.26; 95% CI, 0.12-0.61 [P = .002]) were found to be independently associated with OS after disease recurrence. Surgical salvage was independently associated with improved OS compared with nonsurgical treatment among patients with both locoregional (aHR, 0.15; 95% CI, 0.04-0.56 [P = .005]) and distant (aHR, 0.19; 95% CI, 0.05-0.75 [P = .018]) metastatic disease recurrences.
  
  
  CONCLUSIONS
  Surgical salvage was found to be associated with improved OS for patients with recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data are needed to confirm the role of surgical salvage for distant metastases.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Theresa
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Qualliotine
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Milton J. Dance, Jr. Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Ha
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Milton J. Dance, Jr. Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Milton J. Dance, Jr. Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
authors.forename: John R
authors.initials: JR
authors.lastname: Saunders
authors.affiliation: Milton J. Dance, Jr. Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
authors.forename: Ray G
authors.initials: RG
authors.lastname: Blanco
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
authors.affiliation: Division of Oncology Biostatistics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Ana
authors.initials: A
authors.lastname: Kiess
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Gourin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Wayne
authors.initials: W
authors.lastname: Koch
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Milton J. Dance, Jr. Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Richmon
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: David W
authors.initials: DW
authors.lastname: Eisele
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.|Milton J. Dance, Jr. Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000601:surgery* / Q000821:virology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000601:surgery* / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000601:surgery* / Q000821:virology*; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000601:surgery* / Q000821:virology*; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis
keywords: disease recurrence; human papillomavirus; neoplasm metastasis; oropharyngeal neoplasms; salvage therapy; squamous cell carcinoma of the head and neck