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

doi:10.3877/cma.j.issn.1674-1366.2026.02.009

Abstract

Abstract:

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

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]. Chinese Journal of Stomatological Research(Electronic Edition), 2026, 20(02): 136-148.

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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

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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