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

Brian O'Sullivan*, Shao Hui Huang, Jie Su, Adam S. Garden, Erich M. Sturgis, Kristina Dahlstrom, Nancy Lee, Nadeem Riaz, Xin Pei, Shlomo A. Koyfman, David Adelstein, Brian B. Burkey, Jeppe Friborg, Claus A. Kristensen, Anita B. Gothelf, Frank Hoebers, Bernd Kremer, Ernst-Jan Speel, Daniel W. Bowles, David RabenSana D. Karam, Eugene Yu, Wei Xu

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background 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. Methods 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. Findings 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
Original languageEnglish
Pages (from-to)440-451
JournalLancet oncology
Issue number4
Publication statusPublished - Apr 2016

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