Although tumor HPV status is often regarded as a prognostic biomarker due to dramatic differences in outcomes between HPV-related (HPV+) and unrelated (HPV–) oropharyngeal cancers (OPCs), its true role is as a diagnostic biomarker. In essence, HPV distinguishes two fundamentally different diseases affecting different populations with different clinical and outcome profiles. Although different in so many ways, they still use the same TNM classification (7th edition TNM, TNM-7ed). Emerging evidence suggests that TNM-7ed is inadequate to properly depict prognosis for HPV+ OPC patients. In addition, although current clinical trials address both diseases separately, clinicians and researchers are experiencing uncertainty in defining eligibility criteria for patient’s selection. Consequently, opinions have converged on the principle that an HPV+ OPC specific staging system is urgently needed to properly depict the character and prognosis of this disease. The objective of this presentation is to assess the need for a new stage classification for HPV+ OPC.
A single-center cohort (a “Discovery cohort”) formed the foundation to evaluate adequacy of TNM-7ed in HPV+ and HPV– OPC patients, suggesting a hypothesis that the current TNM-7ed is inadequate for HPV+ OPC; the study also assessed the feasibility of a proposed new stage classification for HPV+ OPC. The hypothesis was subsequently examined in a multi-centre setting (“Confirmatory Study”) where the “Training Cohort” was chosen from the original centre and datasets from 6 additional institutions drawn from Europe and North America formed a “Validation Cohort”. Finally, heterogeneity tests were performed to assess the performance of the new TNM classification.
The multi-center “Confirmatory Study” based on the “Discovery Study” hypothesis proposed a new staging for HPV+ OPC. This used a Training-Validation design incorporating nearly 2000 HPV+ OPC treated from 7 institutions and two continents (North America and Europe). The major difference in the new stage classification for HPV+ OPC is that the N-categories resemble those used for nasopharyngeal cancer (NPC) excepting lower-neck lymph node involvement (a unique feature of the NPC classification). Heterogeneity tests confirmed that this hypothesis-based study upholds validity under various treatment protocols and jurisdictions.
Current TNM staging is inadequate for HPV+ OPC in predicting prognosis. A new stage classification for HPV+ OPC is needed. The newly proposed TNM classification permits a more appropriate depiction of the character and prognosis of this disease.
Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L, et al. Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus-Related Oropharyngeal Carcinomas. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;33(8):836-45. Epub 2015/02/11.
O’Sullivan B, Huang SH, Su J, Garden A, 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 E-J, Bowles DW, Raben D, Karam SD, Yu E, Xu W. A Proposal for UICC/AJCC Pre-treatment TNM Staging for HPV-related Oropharyngeal Cancer by the International Collaboration on Oropharyngeal Cancer Network for Staging (ICON-S): A Comparative Multi-Centre Cohort Study. Lancet Oncol. (accepted). Nov 27, 2015.