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 ... -  《-》

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 ... -  《-》

Evaluation of proposed staging systems for human papillomavirus-related oropharyngeal squamous cell carcinoma.

Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) have improved survival when compared with those with HPV-negative OPC. Unfortunately, the American Joint Committee on Cancer seventh edition (AJCC-7ed) staging system does not account for the prognostic advantage observed with HPV-positive OPC. The purpose of the current study was to validate and compare 2 recently proposed staging systems for HPV-positive OPC. Patients treated for HPV-positive OPC from 2005 to 2015 at Johns Hopkins Hospital (JHH) were included for analysis. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) and The University of Texas MD Anderson Cancer Center (MDACC) staging systems were applied and survival was calculated using Kaplan-Meier methods. Cox proportional hazard regression was used to determine the relationship between stage of disease and survival. Models were compared using the Akaike information criterion (AIC). A total of 435 patients were eligible for analysis. There was a dramatic shift in lymph node category and overall stage of disease when ICON-S and MDACC stage were applied to the JHH cohort. There was superior stratification of overall survival and progression-free survival by ICON-S stage. Both proposed models had an improved fit based on AIC scores (P<.001 for both) over the AJCC-7ed. The ICON-S staging system had the lowest AIC score, and thus a better fit within the JHH population. The current analysis provides external validation for both staging systems in an independent and heterogeneously treated patient population. Although the MDACC staging system is an improvement over the AJCC-7ed, the ICON-S stage provides superior stratification of overall and progression-free survival, thereby supporting its use as the updated AJCC staging system for OPC. Cancer 2017;123:1768-1777. © 2017 American Cancer Society.

Malm IJ ，Fan CJ ，Yin LX ，Li DX ，Koch WM ，Gourin CG ，Pitman KT ，Richmon JD ，Westra WH ，Kang H ，Quon H ，Eisele DW ，Fakhry C ... -  《-》

Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study.

Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer. The ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification. Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p<0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p<0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages. Our proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification. None.

O'Sullivan B ，Huang SH ，Su J ，Garden AS ，Sturgis EM ，Dahlstrom K ，Lee N ，Riaz N ，Pei X ，Koyfman SA ，Adelstein D ，Burkey BB ，Friborg J ，Kristensen CA ，Gothelf AB ，Hoebers F ，Kremer B ，Speel EJ ，Bowles DW ，Raben D ，Karam SD ，Yu E ，Xu W ... -  《-》

Confirmation of proposed human papillomavirus risk-adapted staging according to AJCC/UICC TNM criteria for positive oropharyngeal carcinomas.

Patients with human papillomavirus (HPV)-related oropharyngeal cancers (OPCs) have superior outcomes in comparison with patients with non-HPV-induced OPCs. This study confirms that a previously proposed HPV risk-adapted restaging system better reflects disease outcomes. The National Cancer Data Base was used to analyze 8803 HPV+ OPC patients. Univariate and multivariate analyses were performed to identify the utility of both American Joint Commission on Cancer (AJCC) staging and HPV risk-adapted staging in predicting the outcomes of patients with HPV+ OPC and other factors influencing survival. With a median follow-up of 27.1 months, 3.2% had AJCC stage I disease and 6.6%, 19.4%, and 70.9% had stage II, III, and IV disease, respectively. When the patients were restaged according to HPV risk-adapted staging, 76.6% had stage I disease, 9.9% had stage II disease, and 13.5% had stage III disease. The 4-year overall survival rates according to HPV risk-adapted staging were 85.8%, 77.3%, and 64.6% for stages I, II, and III, respectively, but the rates for AJCC stages I, II, III, and IV were 90.1%, 86.1%, 87.0%, and 80.1%, respectively. Patients with HPV+ metastatic disease at diagnosis had a significantly improved median survival of 20.5 months versus 11.1 months with HPV- disease (P < .01). In the multivariate analysis, survival was also affected by the age at treatment, a nontonsillar or base-of-tongue primary site, private insurance, an annual income ≥ $48,000/y, and the comorbidity index (all P values < .01). Outcomes of HPV+ OPC are significantly improved in comparison with HPV- OPC outcomes, and the current AJCC staging system does not accurately reflect disease outcomes. This study has retrospectively confirmed that an HPV risk-adapted restaging structure more accurately stratifies patients. Under this new risk-stratified staging system, patients may be more accurately stratified for investigation into treatment escalation or de-escalation studies. Cancer 2016;122:2021-30. © 2016 American Cancer Society.

Horne ZD ，Glaser SM ，Vargo JA ，Ferris RL ，Balasubramani GK ，Clump DA ，Heron DE ，Beriwal S ... -  《-》