Appraisal of the AJCC 8th edition pathologic staging modifications for HPV-positive oropharyngeal cancer, a study of the National Cancer Data Base

Background: The American Joint Commission on Cancer (AJCC) recently created new staging for human papillomavirus associated oropharyngeal cancer (HPV+ OPSCC) for its 8th edition. These proposals have not yet been validated in a national registry.

Methods: Review of National Cancer Database (NCDB) for surgically-treated HPV+ OPSCC for years 2010-2014 to validate the new staging system using the Kaplan Meier method to explore survival outcomes.

Results: 3745 cases were analyzed. Median follow-up was 31.3months. Most patients were Caucasian males with tonsillar cancer. Distribution of stage I disease increased from 3.7% to 80.2% in AJCC 8th. pN1 disease shifted from 17.3% to 75.9%. Treatment and distribution of T-stage varied by pathologic nodal (pN) staging. Extranodal extension (ENE) was positive in 41% cases. Four-year overall survival (OS) for AJCC 8th stages I (92%), II (81%), and stage III (62%) showed excellent hazard discrimination (all pairwise p<0.001). Only 4-year OS by pN staging showed significantly different curves when comparing pN2 (79%) with others (pN0 88%; pN1 91%, p=0.01 and <0.001 respectively). Presence of ENE confers a negative effect on overall survival (92% ENE- vs. 85% ENE+, p<0.001).

Conclusion: The NCDB shows improved hazard discrimination and outcome prediction in the AJCC 8th edition staging for HPV+ OPSCC. While overall staging had excellent hazard discrimination, this accounted for poorer discrimination between pN0 and pN1. The majority of patients are reclassified as overall stage I. Presence of extranodal extension demonstrated a statistically significant but modest negative effect on overall survival. CONDENSED ABSTRACT (2 SENTENCES): Using NCDB data for validation, the AJCC 8th ed. pathologic staging system offers much improved hazard discrimination and prognostication in HPV oropharyngeal cancer, with the majority of cases reclassified as pStage I. Of note, only pN2 offered hazard discrimination within nodal staging and presence of pathologic extranodal extension has a modest negative effect on survival.