Clinical vs Microscopic Extranodal Extension and Survival in Oropharyngeal Carcinoma in the Human Papillomavirus Era

Objective Extranodal extension (ENE) is known to be associated with poor outcomes in head and neck squamous cell carcinoma. The objective of this study is to examine the impact of extent of ENE on survival in oropharyngeal carcinoma in the human papillomavirus (HPV) era. Study Design Retrospective database review. Setting Review of the National Cancer Database. Subjects and Methods The National Cancer Database was used to examine surgically treated head and neck squamous cell carcinoma of the tonsil and base of tongue from 2010 to 2015. Nodes available for pathologic examination were classified as ENE negative (-), ENE clinically (+), or ENE (+) on pathology only. The primary outcome was overall survival. Cox regression modeling was used to examine the effect of ENE on survival while controlling for patient demographics, HPV status, stage, adjuvant radiation, and chemotherapy. Results Of the 66,106 patients identified, 16,845 were treated with surgery +/- adjuvant therapy, 8780 of whom were known HPV+. Overall 5-year survival for this group was 86%. Documented ENE was associated with over a 60% decrease in survival for clinical (hazard ratio [HR], 1.63) and pathologic (HR, 1.62) ENE compared to negative ENE, after adjustment for stage, adjuvant radiation +/- chemotherapy, HPV, and other variables. No significant differences were found between clinical and pathologic ENE (HR, 1.001). Conclusion While both surgically resected clinical and pathologic ENE are associated with decreased survival, no significant differences are observed between the two. The impact of these observations on potential de-escalation therapeutic strategies requires further study.