Predictors of Mortality in HPV‐Associated Oropharynx Carcinoma Treated With Surgery Alone

Abstract

Objective Survival outcomes for human papillomavirus‐associated oropharynx squamous cell carcinoma (HPV + OPSCC) treated with surgery alone are unclear. To increase understanding, we assessed overall survival (OS) outcomes using the national cancer database (NCDB). Methods We conducted a retrospective analysis of OS of 736 NCDB HPV + OPSCC patients who underwent surgery alone from 2010 to 2014 using univariate and multivariate analyses and the Kaplan‐Meir method. Results Multivariable analysis found the following independent risk factors for death: American Joint Commission on Cancer (AJCC) 8th edition pathologic stage(p)N2 versus pN0 disease (hazard ratio [HR], 5.5; P = 0.000006), macroscopic extranodal extension (ENE) versus non‐ENE (HR, 4.9; P < 0.02), a positive lymph nodes (LN) percentage of ≥10% (HR, 4.2; P = 0.0002), and five or more positive LNs (HR, 4.9; P = 0.00004). Three‐year OS was significantly worse for AJCC 8th edition pN2 versus pN0 but not for 7th edition pN2 versus pN0 disease. Five‐year OS was significantly worse for positive versus negative surgical margins, AJCC 8th edition stage II versus I, and either microscopic or macroscopic ENE versus non‐ENE positive LNs. For 523 (71%) AJCC 8th edition stage I patients and for 283 (38%) patients who were pT1–T2, with negative margins, pN0–N1, with ≤4 pathologic LNs, without ENE, and with >20 LNs removed during neck dissection, the 3‐year OS rates were 93% and 95%, respectively, and the 5‐year OS rates were 91% and 95%, respectively. Conclusion In the context of the lack of detail and possible inaccuracies found in the NCDB, surgery alone for AJCC 8th edition stage I HPV + OPSCC, particularly pT1–T2, pN0–N1 with ≤4 pathologic LNs, without ENE, and with negative surgical margins has a high OS. Level of Evidence 4 Laryngoscope, 130:E423–E435, 2020

Impact of Lymph Node Yield on Survival in Surgically Treated Oropharyngeal Squamous Cell Carcinoma

“…The association of LVI with poorer survival for the S + CRT group may warrant additional attention. Prior NCDB studies of HPV-related OPSCC did not find an association between LVI and poorer survival in low-risk/surgery-alone cohorts, 30,31 which are distinct from the S + CRT cohort of this study. Studies with larger HPV-related OPSCC NCDB cohorts did not examine LVI as a risk factor.…”

A review of the 8th edition of the AJCC staging system for oropharyngeal cancer according to HPV status

“…Han et al compared the 7th and 8th editions in a study involving 736 HPV-positive patients with OPSCC. When the 7th edition criteria were applied, they found no differences in OS among stage pN0, pN1 and pN2 patients [ 20 ]. Considering the findings described above, there was a clear, urgent need to re-evaluate and modify the staging system in the 7th edition to include HPV status, which would help to ensure adequate discriminative power between the different stages.…”

Significance of Extranodal Extension in Surgically Treated HPV-Positive Oropharyngeal Carcinomas

“…In 2019, Han et al published a retrospective analysis of 736 patients with only surgically treated HPV-positive OPSCC from the NCDB (2010-2014) (43). Among other things, they showed that microscopic or macroscopic ENE results in a significantly worse OS when compared to positive lymph nodes without ENE (5J-OS: 91% vs. 78%; p < 0.0001) (43).…”

“…In 2019, Han et al published a retrospective analysis of 736 patients with only surgically treated HPV-positive OPSCC from the NCDB (2010–2014) ( 43 ). Among other things, they showed that microscopic or macroscopic ENE results in a significantly worse OS when compared to positive lymph nodes without ENE (5J-OS: 91% vs. 78%; p < 0.0001) ( 43 ). In addition, Freitag et al recently published their analysis of a cohort of 92 patients with surgically treated HPV-mediated OPSCC (IC+OP+RT: n = 8, OP: n = 21, OP+RT: n = 23, OP+RCT: n = 39, OP+RT+Cetuximab: n = 1) ( 44 ).…”