Improved TNM Prediction of Survival in HPV‑Related Oropharyngeal Carcinoma


Key Points

  • The current TNM stage grouping did not significantly distinguish overall survival rates in patients with HPV-related disease.
  • Improved prediction of survival was provided by recursive portioning analysis–based TNM stage grouping.

In a study reported in the Journal of Clinical Oncology, Huang et al showed that recursive portioning analysis (RPA) could be used to provide TNM stage grouping with improved prediction of survival in patients with human papillomavirus (HPV)-related nonmetastatic oropharyngeal carcinoma. 

Study Details

The study included data from 573 patients with HPV-related oropharyngeal cancer and 237 with HPV-unrelated disease treated with radiotherapy with or without chemotherapy from 2000 to 2010 at Princess Margaret Hospital, Toronto. For HPV-related disease, RPA was used to derive new RPA stages objectively; the RPA algorithm is based on optimized binary partition of T or N categories, resulting in subgroups with relatively homogeneous survival performance. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR stages, and survival prediction with RPA stage and AHR stage was assessed against the current American Joint Committee on Cancer/Union for International Cancer Control seventh edition TNM stages.

Predictive Ability

Median follow-up was 5.1 years. Among patients with HPV-unrelated disease, 5-year overall survival was lower with higher TNM stage: 70%, 58%, 50%, and 30% for stage I, II, III, and IV (P = .004). However, among patients with HPV-related oropharyngeal carcinoma, there was no significant relationship of stage with survival: 88%, 78%, 71%, and 74% for stage I, II, III, and IV (P = .56).

RPA divided HPV-related disease into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3, with 5-year overall survival of 82%, 76%, and 54% (P < .001). The AHR analysis also yielded significant discrimination of survival, but prediction was better with RPA stage.

RPA-based staging including RPA stage, age, and smoking pack-years produced four prognostic groups: group I (T1-3N0-N2c, ≤ 20 pack-years), group II (T1-3N0-N2c, > 20 pack-years), group III (T4 or N3, age ≤ 70), and group IVA (T4 or N3, age > 70 years), with 5-year overall survival of 89%, 64%, 57%, and 40% (P < .001).

The investigators concluded: “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 [oropharyngeal carcinoma] 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 [oropharyngeal carcinoma].”

Brian O’Sullivan, MD, of Princess Margaret Hospital, is the corresponding author for the Journal of Clinical Oncology article. Shao Hui Huang, MSc, and Wei Xu, PhD, of Princess Margaret Hospital, contributed equally to the study.

The study was supported by the Bartley-Smith/Wharton, Gordon Tozer, Wharton Head and Neck Translational, Dr Mariano Elia, Joe’s Team, and Petersen Funds at the Princess Margaret Foundation. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.