Programmed Death-1/Programmed Death-Ligand 1-Axis Blockade in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Stratified by Human Papillomavirus Status: A Systematic Review and Meta-Analysis.

Yimin Xu,Yong Liu,Donghai Huang,Tanguy Y. Seiwert,Gangcai Zhu,Xin Zhang,Irene X. Y. Wu,Rajarsi Mandal,Christopher A. Maroun

doi:10.3389/fimmu.2021.645170

Abstract

BackgroundProgrammed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors have provided clinical benefit to head and neck squamous cell carcinoma (HNSCC) patients in recent clinical trials. However, it remains unclear as to whether human papillomavirus (HPV) status is associated with improved clinical outcome of anti-PD-1 or anti-PD-L1 immunotherapy in HNSCC.MethodsPubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched up to February 28, 2021. Published clinical trials of HNSCC patients treated with only PD-1 or PD-L1 inhibitors were selected. The primary or secondary outcome of these studies included objective response rate (ORR) stratified by HPV status. The pooled odds ratio (OR) and hazard ratio (HR) were estimated using a fixed-effect model.ResultsA total of seven eligible studies comprising 814 patients were included. The ORR of HPV positive HNSCC patients was significantly higher than that of HPV negative HNSCC patients (OR = 1.77; 95%CI = 1.14-2.74; P = 0.01), and this favorable effect occurred in pooled anti-PD-L1 trials (OR = 2.66; 95%CI = 1.16-6.11; P = 0.02). In comparison, the pooled OR was 1.51 in anti-PD-1 trials (95%CI = 0.90-2.54; P = 0.12). Survival analysis indicated that HPV positive HNSCC patients had a lower risk of overall death as compared to HPV negative HNSCC patients (HR = 0.77; 95%CI = 0.60–0.99; P = 0.04).ConclusionsHPV positive HNSCC patients display improved outcomes with PD-1/PD-L1 axis blockade as compared to HPV negative HNSCC patients. These improved outcomes are likely driven to a greater extent by anti-PD-L1 inhibitors. However, randomized controlled trials with greater numbers of patients are needed for validation of these early findings.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally, with 600,000 cases diagnosed annually and mortality rates as high as 40%–50% [1]
The seven clinical trials included patients treated with anti-Programmed death-1 (PD-1)/ Programmed death-ligand 1 (PD-L1) agents and standard treatment and were comprised of two randomized controlled trials (RCT) and five singlearm trials
We hypothesized that the distinct immunological tumor landscapes of human papillomavirus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) patients might confer a difference in survival rates and tumor response after anti-PD-1/ PD-L1 therapy [36]

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally, with 600,000 cases diagnosed annually and mortality rates as high as 40%–50% [1]. The vast majority of head and neck cancers are squamous cell carcinomas, which arise within different anatomical subsites. Programmed death-ligand 1 (PD-L1) binding to PD-1 on T cells results in suppression of the T cell immune response [7]. Cancer cells may develop several mechanisms of escaping immune-mediated surveillance and death, including surface expression of PD-L1 [8]. Anti-PD-1 and anti-PD-L1 antibodies such as nivolumab, pembrolizumab, cemiplimab, and atezolizumab, durvalumab, avelumab have shown promising results in several cancer types [10, 11]. Programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors have provided clinical benefit to head and neck squamous cell carcinoma (HNSCC) patients in recent clinical trials. It remains unclear as to whether human papillomavirus (HPV) status is associated with improved clinical outcome of anti-PD-1 or anti-PD-L1 immunotherapy in HNSCC

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Results

Conclusion