title: Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas.
abstract: OBJECTIVE
  To refine stage and prognostic group for human papillomavirus (HPV) -related nonmetastatic (M0) oropharyngeal cancer (OPC).
  
  
  METHODS
  All patients with nonmetastatic (M0) p16-confirmed OPC treated with radiotherapy with or without chemotherapy from 2000 to 2010 were included. Overall survival (OS) was compared among TNM stages for patients with HPV-related and HPV-unrelated OPC separately. For HPV-related OPC, recursive partitioning analysis (RPA) derived new RPA stages objectively. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR stages. The performance of survival prediction of RPA stage and AHR stage was assessed against the current seventh edition TNM stages. Prognostic groups were derived by RPA, combining RPA stage and nonanatomic factors.
  
  
  RESULTS
  The cohort comprised 573 patients with HPV-related OPC and 237 patients with HPV-unrelated OPC, with a median follow-up of 5.1 years. Lower 5-year OS with higher TNM stage was evident for patients with HPV-unrelated OPC (stage I, II, III, and IV 5-year OS: 70%, 58%, 50%, and 30%, respectively; P = .004) but not for patients with HPV-related OPC (stage I, II, III, and IV 5-year OS: 88%, 78%, 71%, and 74%, respectively; P = .56). RPA divided HPV-related OPC into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3; 5-year OS: 82%, 76%, and 54%, respectively; P < .001). AHR also yielded a valid classification, but RPA stage demonstrated better survival prediction. A further RPA (including RPA stage, age, and smoking pack-years [PYs]) derived the following four valid prognostic groups for survival: group I (T1-3N0-N2c_≤ 20 PY), group II (T1-3N0-N2c_> 20 PY), group III (T4 or N3_age ≤ 70), and group IVA (T4 or N3_age > 70; 5-year OS: 89%, 64%, 57%, and 40%, respectively; P < .001).
  
  
  CONCLUSIONS
  An RPA-based TNM stage grouping (stage I/II/III: T1-3N0-N2b/T1-3N2c/T4 or N3, with M1 as stage IV) is proposed for HPV-related OPC as a result of significantly improved survival prediction compared with the seventh edition TNM, and prognostication is further improved by an RPA-based prognostic grouping within the American Joint Committee on Cancer/Union for International Cancer Control TNM framework for HPV-related OPC.
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Shao Hui
authors: SH
authors: Huang
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Wei
authors: W
authors: Xu
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: John
authors: J
authors: Waldron
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Lillian
authors: L
authors: Siu
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Xiaowei
authors: X
authors: Shen
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Li
authors: L
authors: Tong
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Jolie
authors: J
authors: Ringash
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Andrew
authors: A
authors: Bayley
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: John
authors: J
authors: Kim
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Andrew
authors: A
authors: Hope
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: John
authors: J
authors: Cho
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Meredith
authors: M
authors: Giuliani
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Aaron
authors: A
authors: Hansen
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Jonathan
authors: J
authors: Irish
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Ralph
authors: R
authors: Gilbert
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Patrick
authors: P
authors: Gullane
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Bayardo
authors: B
authors: Perez-Ordonez
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Ilan
authors: I
authors: Weinreb
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Fei-Fei
authors: FF
authors: Liu
authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, and Brian O'Sullivan, Princess Margaret Cancer Centre, University of Toronto; and Fei-Fei Liu and Brian O'Sullivan, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada. Brian.OSullivan@rmp.uhn.on.ca.
authors: Brian
authors: B
authors: O'Sullivan
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000150:complications* / Q000821:virology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000150:complications* / Q000401:mortality / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D016016:Proportional Hazards Models; D012907:Smoking; D016896:Treatment Outcome