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中华口腔医学研究杂志(电子版)

中华口腔医学研究杂志(电子版) ›› 2026, Vol. 20 ›› Issue (02) : 136 -148. doi: 10.3877/cma.j.issn.1674-1366.2026.02.009

所属专题： 文献；

综述

口腔和口咽鳞状细胞癌免疫治疗相关生物标志物研究现状
江鸿宇1,2, 梁家洛1,2, 马琳1,3, 邓永强1,2, 李星瀚1,3,†()   
  1. 1深圳大学总医院口腔科，深圳　518055
    2深圳大学医学部口腔医学院，深圳　518055
    3深圳大学口腔医学研究所，深圳　518055
  • 收稿日期:2026-02-09 出版日期:2026-04-01
  • 通信作者: 李星瀚

Current advances in biomarkers associated with immunotherapy in oral and oropharyngeal squamous cell carcinoma

Hongyu Jiang1,2, Jialuo Liang1,2, Lin Ma1,3, Yongqiang Deng1,2, Xinghan Li1,3,†()   

  1. 1Department of Stomatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen 518055, China
    2School of Dentistry, Medical School, Shenzhen University, Shenzhen 518055, China
    3Institute of Stomatological Research, Shenzhen University, Shenzhen 518055, China
  • Received:2026-02-09 Published:2026-04-01
  • Corresponding author: Xinghan Li
  • Supported by:
    Basic and Applied Basic Research Foundation of Guangdong Province(2023A1515011945); Science and Technology Planning Project of Shenzhen(JCYJ20240813142112017); HaiYa Young Scientist Foundation of Shenzhen University General Hospital(2025-HY006)
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江鸿宇, 梁家洛, 马琳, 邓永强, 李星瀚. 口腔和口咽鳞状细胞癌免疫治疗相关生物标志物研究现状[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(02): 136-148.

Hongyu Jiang, Jialuo Liang, Lin Ma, Yongqiang Deng, Xinghan Li. Current advances in biomarkers associated with immunotherapy in oral and oropharyngeal squamous cell carcinoma[J/OL]. Chinese Journal of Stomatological Research(Electronic Edition), 2026, 20(02): 136-148.

头颈癌（HNC）是全球常见的恶性肿瘤，其中口腔鳞状细胞癌（OSCC）和口咽鳞状细胞癌（OPSCC）在口腔颌面外科学领域具有较高的发病率和极高的临床关注度。受治疗应答异质性及耐药性等因素影响，HNC患者的总体生存率在近十年来尚未取得显著改善。本文在概述HNC放疗、化疗、免疫治疗、靶向治疗及免疫联合多疗法发展现状的基础上，重点综述了预测OSCC和OPSCC免疫治疗相关的生物标志物研究现状。在放疗和化疗领域，人乳头瘤病毒（HPV）感染状态是目前较为明确的独立预后指标，而液体活检技术的应用为疗效的动态评估提供了新的手段。在免疫治疗方面，虽然程序性死亡-配体1（PD-L1）表达水平和肿瘤突变负荷（TMB）在疗效预测中具有一定参考价值，但肿瘤微环境（TME）的异质性影响了免疫治疗的结局。在靶向治疗领域，尽管以表皮生长因子受体（EGFR）为靶点的治疗已广泛应用，但仍缺乏可靠的预测性生物标志物。通过系统分析不同生物标志物的预测价值及其局限性，本文旨在为OSCC和OPSCC的个体化治疗决策及未来多维生物标志物整合策略提供理论参考。

关键词: 头颈癌, 生物标志物, 免疫治疗, 程序性死亡-配体1

Head and neck cancer (HNC) is a prevalent malignancy worldwide. Notably, oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are characterized by a high incidence rate and garner significant clinical attention within the field of oral and maxillofacial surgery. Constrained by the heterogeneity of therapeutic responses and drug resistance, the overall survival rate of patients with HNC has not witnessed significant improvement over the past decade. This article provides an overview of the current status of radiotherapy, chemotherapy, immunotherapy, targeted therapy, and multidimensional combination therapies. Furthermore, it systematically reviews the research status of predictive biomarkers associated with therapeutic efficacy in OSCC and OPSCC. In the realm of radiotherapy and chemotherapy, human papillomavirus (HPV) infection status remains a well-established independent prognostic factor, while the application of liquid biopsy offers a novel approach for the dynamic evaluation of treatment outcomes. Regarding immunotherapy, although programmed cell death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) possess certain predictive value, the heterogeneity of the tumor microenvironment (TME) significantly influences treatment outcomes. In the field of targeted therapy, despite the widespread clinical application of epidermal growth factor receptor (EGFR) -targeted treatments, reliable predictive biomarkers remain lacking. By systematically analyzing the predictive utility and limitations of various biomarkers, this review aims to provide theoretical references for personalized treatment decision-making and the future development of integrated multidimensional biomarker strategies in OSCC and OPSCC.

Key words: Head and neck cancer, Biomarkers, Immunotherapy, Programmed death-ligand 1
图1 头颈癌（HNC）放疗、化疗、免疫治疗及靶向治疗作用机制示意图　Treg cell：调节性T细胞；NK cell：自然杀伤细胞；CD8+ T cell：CD8+细胞毒性T淋巴细胞；PD-1：程序性死亡受体1；Anti-PD-1：抗PD-1单克隆抗体；PD-L1：程序性死亡-配体1；Anti-PD-L1：抗PD-L1单克隆抗体；EGFR：表皮生长因子受体；Cetuximab：西妥昔单克隆抗体；JAK/STAT通路：Janus激酶-信号转导及转录激活因子通路；PI3K/AKT/mTOR通路：磷脂酰肌醇-3-激酶-蛋白激酶-B-哺乳动物西罗莫司靶蛋白通路。
表1 预测口腔和口咽鳞状细胞癌治疗效果的主要生物标志物总结
治疗方式 生物标志物 预测价值 临床应用现状 主要局限性
放疗、化疗 HPV感染状态[60] 阳性患者总生存率显著改善 独立标志物[55,56,57,58,59] 主要适用于OPSCC，对复发预测能力有限
  ctDNA、cvDNA[73]/ctHPVDNA[74] 动态检测，可预测疗效及复发 研究阶段 新兴技术，检测成本较高
  肿瘤微环境[76,77,78,79] 与耐药相关 研究阶段 临床验证有限
免疫治疗 PD-L1（CPS/TPS）[41,46,86] 预测ICI疗效及生存获益；CPS≥1：FDA批准用于围手术期帕博利珠单抗治疗[85] 最成熟 单独不足以识别所有获益患者
  CTLA-4[91,92] 双重检查点阻断中CPS≥1亚组获益 研究阶段 特定场景适用
  TMB[93] 在CPS不可用时作为PD-L1的补充 ASCO指南推荐 特定人群推荐应用
  CAF[76,99] 特定CAF亚型与免疫治疗敏感性或耐药相关 研究阶段 技术复杂，临床验证有限
  HPV感染状态[101,102] 预测价值仍待明确 未用于治疗决策 临床研究结果不一致
  特定口腔菌群[105] 特定菌群可能通过调节免疫微环境影响疗效 早期研究 新兴热点，需验证
靶向治疗 EGFR表达[106,107] 与西妥昔单抗疗效相关性差 不推荐使用 不可靠
  HPV感染状态[112,113] 阳性患者对西妥昔单抗联合放疗的疗效劣于顺铂联合放疗（复发率更高） 不推荐使用 不适合
  Caveolin-1高表达+SOX2低表达[114] 可预测西妥昔单抗敏感性（PDX准确率88%） 研究阶段 需临床验证
  EMMPRIN（CD147）[23,115] 预测贝伐珠单抗疗效 研究阶段 基于HNSCC的PDX模型研究，数据有限
  CDKN2A/2B缺失[119] 预测CDK4/6抑制剂疗效 研究阶段 数据有限
  突变型p53-MYC-YAP轴[122,123] 增强PI3K抑制剂（如BYL719）敏感性 研究阶段 数据有限
  基线Caspase-3活性[124] 预测mTOR抑制剂疗效 研究阶段 数据有限
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