Microscopic Extranodal Extension in HPV-Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation

Flora Yan, Hong Li, John R. de Almeida, John M. Kaczmar, Patrik Pipkorn, Joseph Zenga, Mary S. Richardson, David M. Neskey, Anand K. Sharma, Terry A. Day, Evan M. Graboyes

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Objective: Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENEmi) and role of adjuvant concurrent chemoradiation (CRT) for ENEmi remain unclear. This study evaluates (1) the prognostic significance of ENEmi in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. Study Design: Retrospective cohort study. Setting: Commission on Cancer (CoC)–accredited facilities. Methods: This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENEmi or no ENE who had undergone margin-negative surgery. The association of ENEmi with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENEmi receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. Results: We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENEmi. On multivariable analysis, ENEmi was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENEmi who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). Conclusion: For patients with HPV-negative HNSCC, pN+ with ENEmi is associated with worse OS than pN+ without ENE. However, for patients with ENEmi, concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENEmi requires additional investigation.

Original languageEnglish
Pages (from-to)536-549
Number of pages14
JournalOtolaryngology - Head and Neck Surgery (United States)
Issue number4
StatePublished - Oct 2021


  • adjuvant therapy
  • extranodal extension
  • head and neck squamous cell carcinoma


Dive into the research topics of 'Microscopic Extranodal Extension in HPV-Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation'. Together they form a unique fingerprint.

Cite this