New Staging System Proposed for HPV-Related Oropharyngeal Cancer

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 Study
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%).