Validation and assessment of discordance of the 8th edition AJCC (American Joint Committee on Cancer) clinical and pathologic staging systems in patients with p16+ oropharyngeal cancer treated with surgery and adjuvant radiation at a single institution

Abstract

Major updates have been made in the latest (8th) edition of the American Joint Commission on Cancer (AJCC) manual for staging of oropharynx squamous cell cancer (OPSCC)[1, 2] which are based on changes in epidemiology of OPSCC related to the emergence of Human Papilloma Virus (HPV) as the major cause for OPSCC.[3, 4] It is now recognized that patients with HPV positive oropharyngeal cancer (HPV+OPSCC) have superior survival compared to patients with HPV negative oropharynx cancer (HPV-OPSCC).[5] One of the key characteristics of patients with HPV+OPSCC is a markedly improved prognosis despite advanced nodal disease when compared to patients with HPV-disease.[3, 6–8] Traditional risk factors predictive of outcome, such as positive margins and extranodal extension (ENE), are not accurate predictors of outcome in HPV+ patients.[9] Previous studies have reported that the AJCC 7th edition staging system has limited ability to differentiate prognosis accurately among stages in the HPV+OPSCC population.[6–8] As a result, a new clinical staging system (International Collaboration on Oropharyngeal cancer Network for Staging, ICON-S) and a new pathological staging system (HPV-Path) were introduced in 2016 specifically for HPV+OPSCC patients. The ICON-S staging system was developed from a study of 1907 HPV+OPSCC patients using an adjusted hazard ratio model that considered age, smoking status and use of cytotoxic chemotherapy.[10] This staging model was created from data of patients treated primarily with chemoradiation. In contrast, the HPV-Path system was created from a multi-institutional dataset of HPV+OPSCC patients treated with surgery, and thus the staging system was based on pathological variables that were not available in the ICON-S study.[11] The parameters of both staging systems have been incorporated into the new 8th edition of the AJCC staging system for OPSCC.[1, 2] The ICON-S system is the new AJCC 8th edition clinical staging system and the HPV-Path system the pathological staging system. A recent report has suggested the two staging systems result in discordant staging[12] The objective of our study was to validate the new clinical and pathological staging systems in an independent cohort of HPV+OPSCC patients who had received surgery as the initial treatment modality. We also determined which staging system was more appropriate for patients treated with surgery and evaluated the degree of discordance between the clinical and pathological staging systems.