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Influence of resection status on overall survival in p16-positive oropharyngeal carcinoma - a retrospective analysis of cancer registry data

In brief

p16-positive tumors cut death risk by about three quarters, no matter margin

In a registry of 540 surgically treated oropharyngeal cancers, patients with p16-positive tumors survived markedly longer than those without, with roughly a 70% reduction in death risk, and this benefit persisted whether margins were clear (R0) or involved (R1). Resection status alone did not change overall survival, suggesting margin status may be less critical than HPV-related biology, though prospective trials are needed to confirm surgical de-escalation.

Journal
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery (Q1)
Published
19 August 2026
Study design
Cohort / observational study
Evidence level
Level 3, Low (CEBM 3b)
Authors
Theodoros Kazopoulos, Anne von Rüsten, Constanze Schneider, Stephan L Schöbel, Sonia Ziegler, David Alexander Ziegler, et al.
PMID
42618776
DOI
10.1007/s00405-026-10539-8

Why clinicians should know about it

  • Picked for Otorhinolaryngology (paper of the day, 24 August 2026): p16 status outweighs resection margins for overall survival

Abstract

PURPOSE: HPV-associated oropharyngeal squamous cell carcinomas show better treatment response and survival than HPV-negative tumors. Immunohistochemical p16 expression is a validated surrogate for HPV association. While resection status (R0 vs. R1) is traditionally considered prognostic, its interaction with p16 status after primary surgery is unclear. This study evaluated the combined impact of p16 status and resection margins on overall survival. METHODS: A retrospective analysis of the Berlin-Brandenburg cancer registry included patients with non-metastatic OPSCC treated between 2017 and 2023 by primary surgery followed by postoperative radiotherapy with or without systemic therapy. Patients were stratified into four groups: p16-/R0, p16-/R1, p16+/R0, and p16+/R1. Overall survival was assessed using Kaplan-Meier analysis and log-rank testing. Multivariable Cox regression adjusted for age, sex, pT/pN category, ECOG status, systemic therapy, and radiotherapy dose. RESULTS: A total of 540 patients were included (p16-/R0: 142; p16-/R1: 19; p16+/R0: 325; p16+/R1: 54). Among R0 resections, p16-positive tumors showed significantly longer survival than p16-negative tumors (multivariate HR 0.26; p < 0.001). A similar advantage for p16-positive vs. p16-negative tumors was observed in R1 resections (multivariate HR 0.35; p = 0.030). Resection status (R1 vs. R0) was not significantly associated with survival in p16-negative (HR 0.86; p = 0.706) or p16-positive tumors after multivariable adjustment (HR 1.74; p = 0.112). CONCLUSION: p16 status was a stronger prognostic factor than resection margins. Overall survival did not differ significantly between R0 and R1 resection after multivariable adjustment. These results support further prospective testing into surgical de-escalation strategies. Just accepting an R1 margin would shift treatment burden towards intensified adjuvant therapy rather than reduce it.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.