Research in context
Evidence before this study
Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. To date, most prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease, which affects a disparate population of patients and is anticipated to require different treatments. Opinions have converged on the principle that a novel staging system is needed urgently to properly depict the character and prognosis of HPV+ disease, which contrasts with smoking-related (ie, HPV-unrelated [HPV–]) oropharyngeal cancer, from which the 7th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) TNM classification was derived. A challenge in developing a new TNM classification is to obtain an adequate study sample covering the full disease spectrum (including early to advanced stages). Most trials in head and neck cancer have, in general, addressed locally advanced disease only, and trials specific to oropharyngeal cancer are scarce. Trials also lack HPV-specific data, as do administrative and registry data sources.
Added value of this study
The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) study represents an international effort to develop a pretreatment TNM clinical staging classification for HPV+ oropharyngeal cancer. The ICON-S study included almost 2000 patients with HPV+ oropharyngeal cancer from seven institutions across Europe and North America. Heterogeneity tests showed that hazard ratios for stage III versus II disease, and for stage II versus I disease, were in the same direction (>1·0 for higher stages) across all institutions, which supports applicability of the ICON-S classification across various patient populations.
Implications of all the available evidence
At the present time, most patients with HPV+ oropharyngeal cancer are told they have stage IV disease, but the reality is that their outlook is similar to that of patients with the most curable malignant diseases. This situation is alarming for many patients when first faced with their diagnosis and might perpetuate the idea that traditional intensified treatments are always needed—a notion that is being challenged. The proposed ICON-S classification for HPV+ oropharyngeal cancer permits a more appropriate depiction of prognosis of HPV+ disease than is available with the 7th edition of the UICC/AJCC TNM classification. Moreover, the ICON-S classification will enhance stratification into more appropriate groups to both facilitate translational research and optimise clinical trial design and outcome reporting.