Advancing lymph node metastasis in head and neck squamous cell carcinoma: Integrative mechanisms, emerging diagnostics, and translational therapies.

Lymph nodes (LNs) play a critical role in the process of cancer metastasis, serving as pivotal hubs for the retention, proliferation, and immune regulation of metastatic cells, and promoting distant metastasis through various mechanisms. Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive malignancy, where lymph node metastasis (LNM) is a key indicator of disease progression and poor prognosis, directly impacting patient survival and quality of life. Understanding the complex mechanisms of lymph node metastasis, precise diagnostic methods, and effective therapeutic strategies is essential for improving HNSCC patient outcomes. This review explores the formation of pre-metastatic niches, lymphangiogenesis, epithelial-mesenchymal transition (EMT), and the functions and molecular mechanisms of various cell types within the tumor microenvironment (TME) related to lymph node metastasis in HNSCC. It also comprehensively summarizes different diagnostic approaches (including traditional imaging techniques, radiomics, histopathological analysis, advancements in liquid biopsy, the application of targeted imaging probes, and multi-omics technologies) and various therapeutic strategies (such as surgical interventions, radiotherapy, chemotherapy, targeted therapy, and immunotherapy), aiming to provide important scientific evidence for the precise diagnosis and comprehensive treatment strategies for patients with lymph node metastasis.