Understanding the impact of survival and human papillomavirus tumor status on timing of recurrence in oropharyngeal squamous cell carcinoma

• We examine the role of survival bias in relating HPV and timing of recurrence.
• A stratified analysis shows how late survivorship is associated with late recurrence.
• Late survivors, independent of HPV tumor status, may experience late recurrences.

ObjectivesHuman 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.Materials & methodsA 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.ResultsIn 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).ConclusionsLate 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.