title: Understanding the impact of survival and human papillomavirus tumor status on timing of recurrence in oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  Human papillomavirus (HPV)-positive tumor status is associated with improved prognosis after disease recurrence in oropharyngeal squamous cell carcinoma (OPSCC). In this study the potential role of survival bias in the relationship between HPV tumor status and the timing of recurrence was evaluated, given conflicting evidence in the literature.
  
  
  METHODS
  A secondary analysis was performed on a previously published retrospective two institution study of recurrent OPSCC with known HPV tumor status. Patients were categorized as "early" (surviving <24 months) or "late" survivors (⩾24 months). Timing of first recurrence and overall survival were analyzed using Kaplan-Meier and cox proportional hazard methods. Two-sided p-values <0.05 were considered significant.
  
  
  RESULTS
  In total 101 patients met criteria including 81 late and 20 early survivors. HPV-positive tumor status was associated with longer time to recurrence in late survivors (median 21.8 vs. 13.8 months, p=0.028). Late survivors had later recurrences in HPV-positive (p<0.001) and HPV-negative patients (p=0.0096), as well as in both locoregional (p<0.0001) and distant metastatic recurrence (p<0.0001). In multivariate analysis, both HPV-positive tumor status (adjusted HR [aHR] 0.48, p=0.006) and survival beyond 24 months (aHR 0.21, p<0.001) were associated with later recurrence. When stratified, HPV tumor status was only associated with later recurrence in late survivors (aHR 0.47, p=0.015).
  
  
  CONCLUSIONS
  Late survivorship was associated with late recurrence for both HPV-positive and HPV-negative patients. Stratification by survival illustrates how survival bias links late survivorship with late recurrences and contributes to our understanding of the impact of HPV tumor status on the timing of recurrence.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Rettig
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA; Milton J. Dance Jr. Head and Neck Center, Baltimore, MD 21204, USA; Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. Electronic address: cfakhry@jhmi.edu.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D009959:Oropharyngeal Neoplasms / Q000401:mortality*; D030361:Papillomavirus Infections / Q000401:mortality*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
keywords: Human papillomavirus; Metastasis; Oropharynx cancer; Recurrence