The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) developed a TNM classification specific to human papillomavirus (HPV)-related oropharyngeal cancer.1

The proposed model is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification although more study is needed to determine whether T and N categories should be further refined.

Researchers sought to develop a TNM classification specific to HPV-positive oropharyngeal cancer because many prognostic algorithms use HPV status as a stratification factor, ignoring the uniqueness of HPV-positive cancers.

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A total of 1907 patients with HPV-positive oropharyngeal cancer from 7 cancer centers across Europe and North American were included in the study. One center served as the training cohort (661 patients; 35%) and 6 were in the validation cohorts (1246 patients; 65%).

Overall survival at 5 years was compared between the training and validation cohorts. Recursive partitioning analysis and adjusted hazard ratio modeling methods were used to derive new staging classifications.

Results showed that 5-year overall survival was similar for 7th edition TNM stage 1, 2, 3, and 4a (respectively; 88% [95% CI, 74 – 100]; 82% [71 – 95]; 84% [79 – 89]; and 81% [79 – 83]; global P = .25) but was lower for stage 4b (60% [53 – 68]; P < .0001).

Five-year overall survival did not differ among NO, N1-N2a, and N2b subsets, but was significantly lower for patients with N3 disease. The N categories were re-termed: ICON-S NO, 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.

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Five-year overall survival was also similar among patients classed as T4a and T4b, therefore investigators no longer subdivided T4 in the re-termed ICON-S T categories. The proposed ICON-S classification is stage 1 (T1-T2N0-N1), stage 2 (T1-T2N2 or T3N0-N2), and stage 3 (T4 or N3); stage 4 (metastatic disease).


  1. O’Sullivan B, Huang SH, Su J, et al. 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 [published online ahead of print February 26, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00560-4.