Currently, all oropharyngeal cancers (OPC), whether HPV-positive or HPV-negative, use the 7th edition Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) TNM staging system. Patients with HPV-positive cancers have higher overall survival than their HPV-negative counterparts by a wide margin, however. This disparity in overall survival affects outcomes research and interferes with clinical decision making because prognosis is not reflected by the current system.
Researchers of a report published earlier this year propose a new staging system for human papillomavirus (HPV)-related OPC (Lancet. 2016;17:440-451). The authors developed the system based on findings from the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) study.
The researchers explored alternative staging criteria based on current TNM staging, which is based on the tumor (T category), whether or not the cancer has reached nearby lymph nodes (N category), and metastasis (M category).
The investigators showed that applying the current TNM staging criteria to patients with HPV-positive cancers did not take into account the uniqueness of this particular cancer. They did not find differences in survival between stage groups, and the distribution of patients was unbalanced; the current criteria classified the majority of patients as having stage IV disease. Thus, they sought to develop a revised staging system that would separate patients with HPV-related OPC.
“Staging is a critical component of designing treatment plans and for predicting and helping patients understand their prognosis,” said Erich M. Sturgis, MD, professor in the department of head and neck surgery at The University of Texas MD Anderson Cancer Center in Houston and co-author of the study. “Patients with HPV-positive OPC tend to present with more advanced disease, but also typically have better survival rates than those with HPV-unrelated OPC. These cancers are markedly different and require different staging criteria.”
The ICON-S study, an international effort to develop a pretreatment TNM clinical staging classification specific to HPV-positive OPC, studied 1,907 patients from seven institutions in Europe and North America, including one training center (n = 661) and six validation centers (n = 1,246). Investigators included patients with newly diagnosed non-metastatic OPC undergoing either primary surgery or primary radiotherapy with or without chemotherapy and determined HPV status with p16 staining or in situ hybridization.
Among all patients, according to the UICC/AJCC staging system, the five-year overall survival rate was similar among those with TNM stage I (88%), II (82%), III (84%), and IVA disease (81%) but significantly lower in those with stage IVB disease (60%). For N stage, five-year overall survival was similar for N0 (80%), N1–N2a (87%), and N2b (83%) but was significantly lower for N3 disease (59%). No difference in five-year survival was found between T4a and T4b disease (58% versus 57%).
The New Staging
In the new system, the 7th edition N categories were reclassified as follows:
• ICON-S N0 = no lymph nodes involved;
• ICON-S N1 = ipsilateral lymph nodes;
• ICON-S N2 = bilateral or contralateral lymph nodes; and
• ICON-S N3 = lymph nodes > 6 cm (with no subdivision of T4 disease).
The new proposed ICON-S classification consists of the following stages:
• stage I (T1–T2N0–N1);
• stage II (T1–T2N2 or T3N0–N2); and
• stage III (T4 or N3) (with metastatic disease classified as stage IV).
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 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 versus five or more involved nodes across ICON-S stages.
The authors of the study say that ICON-S stage classification predicts prognosis in different jurisdictions. Historical data can be converted readily into the ICON-S classification. They also anticipate that the ICON-S TNM will address the other aims of staging beyond prognostication, including determining clinical trials eligibility and stratification, monitoring adherence to clinical guidelines, assessing treatment outcome, facilitating translational research, and supporting cancer control activities.