Hospital-Based Registry Analysis of Staging Efficacy and Proposed Staging Subclassification for Stage I HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Objectives: AJCC8 introduced separate staging for HPV-associated OPSCC in 2018 to enhance prognostic discrimination. Consequently, most patients previously staged I-IVA in AJCC7 were reclassified as stage I. This study aimed to stratify AJCC8 stage I HPV-associated OPSCC patients using AJCC7 criteria to assess hazard consistency. Materials and Methods: The NCDB was queried for patients diagnosed with AJCC7 T1-2 N0-2b HPV-associated OPSCC during 2010–2016 who met criteria to be restaged to AJCC8 overall stage I. Cox-proportional hazards models including AJCC7 T and N stage as covariates were generated to test for significant predictors of 5-year overall survival in patients with stage I disease according to AJCC8, which were then used to generate substages. Results: A total of 5,737 patients with AJCC7 cT1-2 N0-2b HPV-associated OPSCC were identified. A multivariable Cox-proportional hazards model showed a significant association of cT2 (HR, 95 % CI, P) (1.8, 1.4–2.2, P < 0.001) compared to cT1, and cN2b (1.4, 1.1–1.7, P = 0.002) compared to less than cN2b (i.e. cN0, cN1, cN2a) with 5-year OS. These results were used to generate substages of AJCC8 stage I: cT1N0-2a were designated stage IA, cT2N0-2a and cT1N2b as stage IB, and cT2N2b as stage IIA. Log-rank testing between these substages revealed significant differences between the respective survival curves at 5 years (P < 0.001 for all comparisons). Conclusion: Substaging of AJCC8 stage I for HPV-associated OPSCC by cT2 and cN2b (7th edition TNM stage) provided significant hazard consistency. Adoption may improve prognostic risk stratification and inform guidance in treatment decision making. Further validation of this staging is warranted.