Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
School of Medicine, South China University of Technology, Guangzhou, China.
Sci Rep. 2019 Sep 16;9(1):13404. doi: 10.1038/s41598-019-49771-0.
Chemotherapy and radiotherapy predominantly improve the clinical outcomes of patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC). Whether this superiority goes on when treated with immune checkpoint inhibitors is still unclear. This study sought to determine the predictive value and potential mechanisms of HPV status for the treatment of programmed cell death 1 (PD-1)/ligand 1(PD-L1) inhibitors. We conducted an integrated analysis of the relationships between HPV status and PD-L1, tumor mutation burden (TMB) and inflammation-related immune cells and molecules, based on the analysis of repository databases and resected HNSCC specimens. The pooled analysis of overall survival (OS) and objective response rate (ORR) suggested that HPV-positive patients benefited more from PD-1/PD-L1 inhibitors than HPV-negative patients (OS: hazard ratio (HR) = 0.71, p = 0.02; ORR: 21.9% vs 14.1%, odds ratio (OR) = 1.79, p = 0.01). Analysis of public databases and resected HNSCC specimens revealed that HPV status was independent of PD-L1 expression and TMB in HNSCC. However, HPV infection significantly increased T-cell infiltration, immune effector cell activation and the diversity of T-cell receptors. Notably, HPV-positivity correlated with increased immune cytolytic activity and a T-cell-inflamed gene expression profile. This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection.
化疗和放疗主要改善了人乳头瘤病毒（HPV）相关头颈部鳞状细胞癌（HNSCC）患者的临床结局。当使用免疫检查点抑制剂治疗时，这种优势是否持续尚不清楚。本研究旨在确定 HPV 状态对程序性细胞死亡 1（PD-1）/配体 1（PD-L1）抑制剂治疗的预测价值和潜在机制。我们基于对存储库数据库和切除的 HNSCC 标本的分析，对 HPV 状态与 PD-L1、肿瘤突变负担（TMB）和炎症相关免疫细胞和分子之间的关系进行了综合分析。总生存（OS）和客观缓解率（ORR）的汇总分析表明，HPV 阳性患者从 PD-1/PD-L1 抑制剂中获益多于 HPV 阴性患者（OS：风险比（HR）=0.71，p=0.02；ORR：21.9% vs 14.1%，优势比（OR）=1.79，p=0.01）。对公共数据库和切除的 HNSCC 标本的分析表明，HPV 状态与 HNSCC 中的 PD-L1 表达和 TMB 无关。然而，HPV 感染显著增加了 T 细胞浸润、免疫效应细胞激活和 T 细胞受体的多样性。值得注意的是，HPV 阳性与增加的免疫细胞毒性活性和 T 细胞炎症基因表达谱相关。这项工作提供了证据表明，HPV 状态可用于预测 PD-1 抑制剂在 HNSCC 中的有效性，而与 PD-L1 表达和 TMB 无关，并且可能是由 HPV 感染引起的炎症免疫微环境引起的。
