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.

A matched comparison of human papillomavirus–induced squamous cancer of unknown primary with early oropharynx cancer

“…Although imputation of HPV status in the CUP cohort introduces uncertainty that this study may have included HPV‐negative patients, this risk is low as demonstrated by the validated model above and supported by the anatomic distribution of nodal disease in the imputed cohort. Furthermore, the imputation of HPV status has been used in the past to improve statistical power . In the unlikely (<1 in 5) event of a false‐positive inclusion (i.e., inclusion of a patient who was truly HPV negative), this erroneously included patient's risk of recurrence or death would likely be higher than a true HPV‐positive patient, further reinforcing our conclusions that HPV‐induced CUP patients have an excellent prognosis, similar to HPV‐induced OPX cancer.…”

Effect of HPV on head and neck cancer patient survival, by region and tumor site: A comparison of 1362 cases across three continents

“…[4–10] Due to the improved survival in these cases, different staging for HPV-related oropharyngeal cancers has even been proposed,[11,12] and several HPV-OPSCC de-escalation trials are being conducted. [13,14] However, recurrence remains an issue for HPV-related OPSCC patients, and it is unclear which patients may benefit from de-escalated therapy or de-intensified follow-up. Many questions remain, including whether HPV-related biomarkers also have utility in identifying better survival among non-oropharyngeal HNSCC.…”

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017

“…42, 43 Therefore, consensus is increasing that HPV status should be used as a stratification factor or be addressed in separate trials (HPV-related vs -unrelated disease) for which patients with oropharyngeal cancer are eligible. [44][45][46] Some clinicians have recently suggested that less-intense treatment may be adequate for HPV-positive oropharyngeal cancers (ie, deintensification) 47 ; however, the available data supporting this assertion are limited by retrospective analyses, variability in HPV testing method used, and short follow-up periods. 42,[47][48][49] Deintensification treatment protocols for HPV-associated, locally advanced oropharyngeal cancer are being investigated in ongoing clinical trials.…”