Proposed Staging System for Patients With HPV-Related Oropharyngeal Cancer Based on Nasopharyngeal Cancer N Categories

Abstract

Purpose: Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) generally present with more advanced disease but have better survival than patients with HPV-unrelated OPC. The current American Joint Commission on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system for OPC was developed for HPV-unrelated OPC. A new staging system is needed to adequately predict outcomes of patients with HPV-related OPC.

Patients and methods: Patients with newly diagnosed HPV-positive OPC (by p16 immunohistochemistry or in situ hybridization) treated at our institution from January 2003 through December 2012 were included. By using recursive partitioning analysis (RPA), we developed new stage groupings with both traditional OPC regional lymph node (N) categories and nasopharyngeal carcinoma (NPC) N categories. Survival was estimated by the Kaplan-Meier method, and the relationship between stage and survival was examined by using Cox proportional hazards regression analysis.

Results: A total of 661 patients with HPV-positive OPC met the inclusion criteria. With the traditional TNM staging system, there was no difference in survival between stages (P = .141). RPA with NPC N categories resulted in more balanced stage groups and better separation between groups for 5-year survival than RPA with traditional OPC N categories. With the stage groupings that were based in part on NPC N categories, the risk of death increased with increasing stage (P for trend < .001), and patients with stage III disease had five times the risk of death versus patients with stage IA disease.

Conclusion: New stage groupings that are based on primary tumor (T) categories and NPC N categories better separate patients with HPV-positive OPC with respect to survival than does the current AJCC/UICC TNM staging system. Although confirmation of our findings in other patient populations is needed, we propose consideration of NPC N categories as an alternative to the traditional OPC N categories in the new AJCC/UICC TNM staging system that is currently being developed.

Fig 1.

Stage groups for human papillomavirus –positive (HPV+) oropharyngeal cancer (OPC) that are based on recursive partitioning analysis (RPA) with nasopharyngeal cancer N categories. (A) Stage groups and 5-year overall survival (OS) estimates. (B) Diagram of proposed stages (stage IV would be reserved for patients with M1 disease).

Fig 2.

Kaplan-Meier curves for overall survival (A) and progression-free survival (B) among patients with human papillomavirus (HPV) –positive oropharyngeal cancer by using proposed stage groups that are based on recursive partitioning analysis (RPA) with nasopharyngeal cancer regional lymph node categories.

Fig A1.

Patient selection diagram that shows the median age, percentage who were men, and percentage of ever-smokers for patients excluded from and included in the analysis. HPV, human papillomavirus; IMRT, intensity-modulated radiation therapy; OPC, oropharyngeal cancer.

Fig A2.

Kaplan-Meier curve for overall survival among patients with human papillomavirus (HPV) –positive oropharyngeal cancer (OPC) by current American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM stage groups.

Fig A3.

Kaplan-Meier curves for overall survival (A) and progression-free survival (B) among patients with human papillomavirus (HPV) –positive oropharyngeal cancer (OPC) by stage groups that are based on recursive partitioning analysis (RPA) proposed by Huang et al (stage I: T1-3, N0-N2b; II: T1-3, N2c; III: T4 or N3).

Fig A4.

Stage groups for p16-positive oropharyngeal cancer (OPC) that are based on recursive partitioning analysis (RPA) with nasopharyngeal cancer regional lymph node categories. (A) Stage groups and 5-year overall survival (OS) estimates. Kaplan-Meier curves for overall survival (B) and progression-free survival (C) among patients with p16-positive OPC by using proposed stage groups that are based on RPA with nasopharyngeal cancer N categories.