New Staging System for Human Papillomavirus–Related Oropharyngeal Cancer


Key Points

  • The ICON-S staging system is a new system specific to human papillomavirus–related disease.
  • In the new system, N categories are reclassified as ICON-S N0 = no lymph nodes, N1 = ipsilateral lymph nodes, N2 = bilateral or contralateral lymph nodes, and N3 = lymph nodes > 6 cm, with no subdivision of T4 disease.

As reported in The Lancet Oncology by O’Sullivan et al, a new staging system for human papillomavirus–related oropharyngeal cancer has been developed based on findings from the International Collaboration on Oropharyngeal Cancer Network for Staging (ICON-S) study.

Study Details

The study included 1,907 patients with human papillomavirus–positive disease from 7 centers in the United States and Europe, consisting of a training center (n = 661) and validation centers (n = 1,246). The status of human papillomavirus was determined with p16 staining or in situ hybridization.

Changes to TNM Staging

Among all patients, according to the 7th edition of the Union for International Cancer Control/American Joint Committee on Cancer [UICC/AJCC] staging system, 5-year overall survival was similar among those with TNM stage I (88%), II (82%), III (84%), and IVA disease (81%; global P = .25) but significantly lower in those with stage IVB disease (60%, P < .0001). For N stage, 5-year overall survival was similar for N0 (80%), N1–N2a (87%), and N2b (83%) but was significantly lower for N3 disease (59%, P < .0001). No difference in 5-year survival was found between T4a and T4b disease (58% vs 57%).

In the new system, the 7th edition N categories were reclassified as ICON-S N0 = no lymph nodes involved, N1 = ipsilateral lymph nodes, N2 = bilateral or contralateral lymph nodes, and N3 = lymph nodes > 6 cm, with no subdivision of T4 disease. The new proposed ICON-S classification consists of stage I (T1–T2N0–N1), stage II (T1–T2N2 or T3N0–N2), and stage III (T4 or N3), with metastatic disease (M1) classified as stage IV. In an adjusted hazard ratio [HR] model including all patients, hazard ratios for death compared with stage I in the new classification were 1.73 (P < .0001) for stage II and 3.78 (P < .0001) for stage III.

In an exploratory training cohort (n = 702), lymph node involvement in the lower neck was significantly associated with survival in ICON-S stage III disease (HR = 2.4, P = .002) but not in stage I or II disease and was not a significant independent predictor. There was no significant difference in survival for less than five vs five or more involved nodes across ICON-S stages.

The investigators concluded: “Our proposed ICON-S staging system for HPV [-related] oropharyngeal cancer is suitable for the 8th edition of the [UICC/AJCC] TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification.”

Brian O’Sullivan, MD, of Princess Margaret Cancer Centre, University of Toronto, is the corresponding author of The Lancet Oncology article.

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