Molecular and clinicopathological predictors of cervical lymph node metastasis in oral squamous cell carcinoma: A narrative review

Abstract

Cervical lymph node metastasis (CLNM) remains the principal determinant of survival in oral squamous cell carcinoma (OSCC), conferring significant reductions in disease-specific and overall survival even in early-stage disease. Despite advances in imaging and surgical staging, accurate identification of occult nodal involvement in clinically node-negative patients continues to represent a major clinical challenge. This narrative review synthesizes contemporary evidence on clinicopathological and molecular predictors of CLNM in OSCC, with emphasis on biological determinants that may refine risk-adapted neck management. A structured literature search of PubMed, Scopus, and Web of Science was conducted, prioritizing high-quality cohort studies, meta-analyses, and translational investigations evaluating histopathological parameters, molecular alterations, tumor microenvironment features, and integrative predictive models. Among clinicopathological factors, depth of invasion, lymphovascular invasion, perineural invasion, tumor budding, and infiltrative invasion patterns consistently demonstrate strong associations with nodal metastasis. Molecular drivers include epithelial–mesenchymal transition, activation of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathway, hypoxia-mediated angiogenesis and lymphangiogenesis, immune checkpoint upregulation, and dysregulated non-coding RNAs. Emerging multivariable models that integrate pathological and molecular determinants demonstrate improved predictive performance compared to conventional tumor–node–metastasis staging. Collectively, CLNM reflects a coordinated biological process involving invasive tumor architecture and molecular reprogramming. Incorporation of validated biological predictors into routine pathological assessment may support precision-based neck management and enhance oncologic stratification in OSCC.

Keywords

Oral squamous cell carcinoma / Cervical lymph node metastasis / Depth of invasion / Tumor budding / Epithelial–mesenchymal transition / Precision neck management

Acknowledgements

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Funding

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Conflict of interest

The author declares no conflicts of interest.

Author contributions

This is a single-authored article.

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