Kumari Swati, Mishra Sridhar, Ali Wahid
Department of Pathology, King George Medical University, Lucknow-226003, Uttar Pradesh, India.
Department of Plastic Surgery, King George Medical University, Lucknow-226003, Uttar Pradesh, India.
J Liq Biopsy. 2025 Jul 25;9:100316. doi: 10.1016/j.jlb.2025.100316. eCollection 2025 Sep.
Oropharyngeal squamous cell carcinoma (OPSCC), particularly the HPV-associated subtype, represents a growing public health burden worldwide. While HPV-positive OPSCC carries a better prognosis, challenges persist in early detection, treatment response monitoring, and recurrence surveillance. Traditional tissue biopsy remains the diagnostic gold standard but is invasive, limited by sampling bias, and unsuitable for dynamic disease monitoring. This review synthesizes current evidence on the role of liquid biopsy including circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), circulating HPV DNA (ctHPV-DNA), circulating tumor cells (CTCs), exosomes, and microRNAs (miRNAs) in the diagnosis, prognostication, and surveillance of OPSCC. A literature review of human studies evaluating circulating biomarkers in OPSCC was performed. Eligible studies included prospective and retrospective investigations using liquid biopsy components for diagnostic, prognostic, or treatment-monitoring applications in HPV-positive or HPV-negative OPSCC. Among the circulating analytes, ctHPV-DNA has emerged as the most robust biomarker in HPV-positive OPSCC, offering high sensitivity and specificity for diagnosis and recurrence detection. Multiple studies support its utility in minimal residual disease (MRD) detection, often predicting recurrence months before clinical evidence. Saliva, plasma, and novel fluids like surgical lymphatic drainage have been evaluated as sampling sources. Additionally, ctDNA somatic mutations, gene methylation signatures, CTC counts, and exosomal miRNAs are being explored for their potential in personalized disease stratification and treatment monitoring. Liquid biopsy is a promising adjunct to tissue biopsy in OPSCC, particularly in HPV-driven disease. Its minimally invasive nature, dynamic tumor tracking capability, and expanding analytical platforms position it as a transformative tool in head and neck oncology. Standardization, assay optimization, and large-scale validation are required before routine clinical integration.
口咽鳞状细胞癌（OPSCC），尤其是与人乳头瘤病毒（HPV）相关的亚型，在全球范围内对公共卫生造成的负担日益加重。虽然HPV阳性的OPSCC预后较好，但在早期检测、治疗反应监测和复发监测方面仍存在挑战。传统的组织活检仍然是诊断的金标准，但具有侵入性，受取样偏差限制，且不适用于疾病的动态监测。本综述综合了目前关于液体活检作用的证据，包括循环肿瘤DNA（ctDNA）、游离DNA（cfDNA）、循环HPV DNA（ctHPV-DNA）、循环肿瘤细胞（CTC）、外泌体和微小RNA（miRNA）在OPSCC诊断、预后评估和监测中的作用。对评估OPSCC循环生物标志物的人体研究进行了文献综述。符合条件的研究包括前瞻性和回顾性调查，这些调查使用液体活检成分用于HPV阳性或HPV阴性OPSCC的诊断、预后评估或治疗监测应用。在各种循环分析物中，ctHPV-DNA已成为HPV阳性OPSCC中最可靠的生物标志物，在诊断和复发检测方面具有高灵敏度和特异性。多项研究支持其在检测微小残留病（MRD）中的效用，通常能在临床证据出现前数月预测复发。唾液、血浆以及手术淋巴引流液等新型液体已被评估为取样来源。此外，正在探索ctDNA体细胞突变、基因甲基化特征、CTC计数和外泌体miRNA在个性化疾病分层和治疗监测中的潜力。液体活检是OPSCC组织活检的一种有前景的辅助手段，尤其是在HPV驱动的疾病中。其微创性质、动态肿瘤追踪能力以及不断扩展的分析平台使其成为头颈肿瘤学中的一种变革性工具。在常规临床应用之前，需要进行标准化、检测优化和大规模验证。
