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

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. 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. 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). 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.

Zhan KY ，Eskander A ，Kang SY ，Old MO ，Ozer E ，Agrawal AA ，Carrau RL ，Rocco JW ，Teknos TN ... -  《-》

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

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). 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. 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. 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. 4 Laryngoscope, 130:E423-E435, 2020.

Han M ，Stanford-Moore GB ，Larson AR ，Schoppy DW ，Cognetti DM ，Joshi AS ，Houlton JJ ，Ryan WR ... -  《-》

Extranodal extension is a strong prognosticator in HPV-positive oropharyngeal squamous cell carcinoma.

To comprehensively examine the prognostic significance of extranodal extension (ENE) in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). Retrospective cohort of cases diagnosed with HPV-positive OPSCC from 2010 to 2015 in the National Cancer Database. Inclusion of all OPSCC HPV-positive cases with appropriate International Classification of Diseases-0-3 codes that received surgery with a neck dissection. Univariate and multivariable analyses were conducted. Hazard ratios (HR) for the independent effects of ENE and N stage on overall survival were estimated by Cox proportional hazards regression. Cases that were ENE-negative had the highest 5-year survival (92.6%; 95% confidence interval [CI]: 90.5%-94.7%). ENE-positive cases had the lowest 5-year survival (84.0%; 95% CI: 80.7%-87.4%). After adjusting for confounding variables, ENE-positivity was associated with almost twice the hazard of death (HR = 1.90; 95% CI: 1.35-2.67) compared to ENE-negative cases. Nodal (N) category 1, ENE-positive status was associated with an increased risk of death (HR = 1.88; 95% CI: 1.26-2.80) compared with N1, ENE-negative status. Compared to N1/ENE-negative cases, N2/ENE-positive cases had the poorest survival (HR: 2.93; 95% CI: 1.94-4.43). Both microscopic and macroscopic ENE were associated with worse outcomes compared to node-positive/ENE-negative status. The implementation of the American Joint Committee on Cancer 8th edition staging system provides a much-improved framework to develop and discuss treatment plans for HPV-positive OPSCC. We feel that careful consideration should be given to the importance of ENE in patients with HPV-positive OPSCC. 4 Laryngoscope, 130:939-945, 2020.

Bauer E ，Mazul A ，Chernock R ，Rich J ，Jackson RS ，Paniello R ，Pipkorn P ，Oppelt P ，Gay H ，Daly M ，El-Mofty S ，Thorstad W ，Adkins D ，Zevallos J ... -  《-》

Confirmation of the eighth edition of the AJCC/UICC TNM staging system for HPV-mediated oropharyngeal cancer in Japan.

Mizumachi T ，Homma A ，Sakashita T ，Kano S ，Hatakeyama H ，Fukuda S ... -  《-》

The applicability of new TNM classification for humanpapilloma virus-related oropharyngeal cancer in the 8th edition of the AJCC/UICC TNM staging system in Japan: A single-centre study.

The purpose of this study is to validate the applicability of new TNM classification for human papillomavirus (HPV)-related oropharyngeal cancer (OPC) in the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system in Japan. A total of 91 OPC patients treated with radiation-based therapy between November 2001 and July 2015 were analyzed retrospectively in this study. HPV infection status was evaluated using tumor p16 expression. 40 OPC patients (44.0%) had HPV-positive disease in this study. The distribution of disease stage of HPV-positive OPC patients dramatically changed from the 7th edition to the 8th edition of AJCC/UICC TNM classification. However, neither the 8th edition nor the 7th edition of the AJCC/UICC TNM staging system could adequately predict outcomes of HPV-positive OPC patients in our patient series. On the other hand, our multivariate analysis indicated that matted nodes and age ≥63 were independent prognostic factors for progression-free survival. In addition, HPV-positive OPC patients with stage I without matted nodes showed significantly better overall and progression-free survival compared with those with stage I with matted nodes and stages II and III in the 8th edition of the AJCC/UICC TNM staging system (P=0.008, and P=0.043, respectively). Our results suggested that matted nodes of HPV-positive OPC patients might be additionally examined to apply the 8th edition of AJCC/UICC TNM classification for more adequate predicting outcomes of HPV-positive OPC patients.

Sano D ，Yabuki K ，Arai Y ，Tanabe T ，Chiba Y ，Nishimura G ，Takahashi H ，Yamanaka S ，Oridate N ... -  《-》