Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma

Parul Sinha, James S. Lewis, Jay F. Piccirillo, Dorina Kallogjeri, Bruce H. Haughey

Research output: Contribution to journalArticle

157 Scopus citations


BACKGROUND: Extracapsular spread (ECS) is commonly used to justify adjuvant chemotherapy in patients with head and neck cancer. The role of ECS as a prognosticator and adjuvant therapy determinant in surgically resected, human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC), however, has never been determined. METHODS: Of 210 oropharynx patients in a prospective transoral laser microsurgery database, 152 patients who had p16-positive primary OPSCC and pathologically positive necks were eligible for the study. ECS was measured from routine reporting (ECS report) and by using a novel histologic grading system (ECS graded). Proportional hazards models and matched analyses were used to compare the impact of ECS and adjuvant therapy on disease-free survival (DFS). Patients with and without graded ECS were matched for T-stage, surgical margins, and adjuvant therapy. RESULTS: At a median follow-up of 43 months, the presence of ECS was not associated with poorer DFS in multivariate analyses (ECS report: hazard ratio [HR], 3.42; 95% confidence interval [CI], 0.45-25.88; P =.23; ECS graded: HR, 2.54; 95% CI, 0.88-7.34; P =.09). T-stage and high-grade ECS, ie soft tissue metastasis (STM graded) were prognostic. Overall and in the presence of ECS or even STM, adjuvant CRT was not associated with better DFS over radiotherapy alone (HR, 0.25; 95% CI, 0.06-1.13; P =.07). In addition, matched analyses demonstrated no significant reduction in DFS for the presence of ECS versus the absence of ECS or reduced DFS for the administration of adjuvant radiotherapy alone versus CRT in ECS-positive patients. CONCLUSIONS: Routinely reported ECS was not prognostic in this study. Adjuvant CRT versus radiotherapy alone produced no improvement in DFS for ECS-positive patients. The authors propose that de-escalated adjuvant therapy should be considered for patients with p16-positive OPSCC who undergo surgery and that routinely reported ECS should not be used to justify adjuvant chemotherapy.

Original languageEnglish
Pages (from-to)3519-3530
Number of pages12
Issue number14
StatePublished - Jul 15 2012


  • adjuvant therapy
  • extracapsular spread, oropharyngeal cancer
  • human papillomavirus
  • lymphatic metastasis
  • p16 protein

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