Immunological Network in Head and Neck Squamous Cell Carcinoma-A Prognostic Tool Beyond HPV Status.

Anna Fialová,Martina Hajdušková,Kamila Hladíková,Radek Špíšek,Vladimír Koucký

doi:10.3389/fonc.2020.01701

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease that affects more than 800,000 patients worldwide each year. The variability of HNSCC is associated with differences in the carcinogenesis processes that are caused by two major etiological agents, namely, alcohol/tobacco, and human papillomavirus (HPV). Compared to non-virally induced carcinomas, the oropharyngeal tumors associated with HPV infection show markedly better clinical outcomes and are characterized by an immunologically “hot” landscape with high levels of tumor-infiltrating lymphocytes. However, the standard of care remains the same for both HPV-positive and HPV-negative HNSCC. Surprisingly, treatment de-escalation trials have not shown any clinical benefit in patients with HPV-positive tumors to date, most likely due to insufficient patient stratification. The in-depth analysis of the immune response, which places an emphasis on tumor-infiltrating immune cells, is a widely accepted prognostic tool that might significantly improve both the stratification of HNSCC patients in de-escalation trials and the development of novel immunotherapeutic approaches.

Highlights

Head and neck squamous cell carcinomas (HNSCCs) are a heterogeneous group of epithelial tumors that are localized in the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx with an estimated global incidence of more than 800,000 new cases per year [1]
In human papillomavirus (HPV)-negative tongue squamous cell carcinoma, the proportions of IL-10+CD19+ Bregs were very low; their levels were significantly enhanced compared to adjacent tissue and were significantly correlated with poor outcome in univariant, but not multivariant, survival analysis [64]
Clinical trials focused on treatment deintensification strategies have not provided the necessary evidence to date to support deintensification protocols

Summary

INTRODUCTION

Head and neck squamous cell carcinomas (HNSCCs) are a heterogeneous group of epithelial tumors that are localized in the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx with an estimated global incidence of more than 800,000 new cases per year [1]. Pan-cancer analyses reveal both HPV-negative and HPV-positive HNSCC as malignancies with a high level of immune cell infiltration [35], HPV-positive OPSCCs show in general markedly higher densities of tumor-infiltrating lymphocytes (TILs) and belong to the immunologically “hottest” of all cancer types [29, 35,36,37]. This feature was reported to be positively correlated with patient survival in a wide range of malignancies [36, 38,39,40,41,42]. Increasing Oropharynx Younger Caucasian Higher 80% Non-keratinizing 86% PIK3CA, DDX3X, CYLD, FGFR Higher

B LYMPHOCYTES

Findings

CONCLUSIONS