Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype

Andreas E Albers,Xu Qian,Annekatrin Coordes,Andreas M Kaufmann

doi:10.1038/s41598-017-16918-w

Abstract

Consistent discrepancies in the p16/HPV-positivity have been observed in head and neck squamous cell carcinoma (HNSCC). It is therefore questionable, if all HPV+ and/or p16+ tested cancers are HPV-driven. Patients down-staged according to the HPV-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion. We performed a meta-analysis to classify clinical outcomes of the distinct subgroups with combined p16 and HPV detection. 25 out of 1677 publications fulfilled the inclusion criteria. The proportion of the subgroups was 35.6% for HPV+/p16+, 50.4% for HPV−/p16−, 6.7% for HPV−/p16+ and 7.3% for HPV+/P16−. The HPV+/p16+ subgroup had a significantly improved 5-year overall-survival (OS) and disease-free-survival in comparison to others both for HNSCC and oropharyngeal cancers. The 5-year OS of the HPV−/p16+ HNSCC was intermediate while HPV+/p16− and HPV−/p16− had the shortest survival outcomes. The clearly distinct survival of HPV−/p16+ cancers may characterize a new relevant HPV-independent subtype yet to be biologically characterized. The possibility also exists that in some HPV+/p16+ cancers HPV is an innocent bystander and p16 is independently positive. Therefore, in perspective, HPV-testing should distinguish between bystander HPV and truly HPV-driven cancers to avoid potential undertreatment in HPV+ but non-HPV-driven HNSCC.

Highlights

Patients down-staged according to the human papillomavirus (HPV)-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion
Given by the nature of HPV-driven tumors, the recently released 8th Edition of the American Joint Committee on Cancer (AJCC) created a separate staging algorithm for high-risk-HPV-associated cancer of the oropharynx distinguishing it from HPV− OPSCC17
We examined the relative risk (RR) of the 5-year OS and disease free survival (DFS) of all subgroups correlating with the HPV+/p16+ and HPV−/p16− groups, depending on the data we extracted from each publication

Summary

Introduction

Patients down-staged according to the HPV-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion. HPV+ tumors have been identified in many regions of head and neck[2,9], especially in oropharyngeal squamous cell carcinomas (OPSCC)[10,11]. These tumors differ from HPV-unrelated cancers at the molecular level[12,13,14,15] and likely, as a consequence, have a much more favorable prognosis, despite the generally more advanced stage at presentation[16]. Because of the differences in biological features and prognosis, individually optimized therapy for patients with HPV-driven tumors would minimize treatment-related toxicity and improve outcomes.

Methods

Results

Conclusion