Leveraging Saliva for Insights into Head and Neck Cancer

Abstract

Head and neck cancer (HNC) represents a heterogeneous group of malignancies with increasing global incidence and notable mortality. Early detection is essential for improving survival rates and minimizing recurrence; however, existing diagnostic methods are often invasive and complex. There is a need for noninvasive and more effective approaches for early detection and real-time monitoring of HNC. Saliva contains various biomolecules that may serve as indicators of HNC. As a result, saliva-based biomarkers have emerged as a transformative approach in the diagnosis and treatment of HNC due to their ease of collection, non-invasiveness, and potential to provide details about biomolecular changes associated with cancer progression. This narrative review synthesizes the current literature on the potential of saliva as a noninvasive diagnostic tool for HNC. It highlights various biomarkers found in saliva, including cell-free DNA, RNA, proteins, and metabolites, and explores emerging technologies in saliva detection that could transform the future of HNC management. Continued research efforts and larger-scale validation studies are essential to fully realize the potential of saliva-based biopsy and help pinpoint notable biomarkers to improve patient outcomes and reduce mortality associated with HNC worldwide.

Keywords: biomarkers; biopsy; diagnosis; head and neck cancer; saliva.

Figure 1

The various components present in saliva and their potential applications. At the center are the salivary glands, surrounded by different biomolecules derived from saliva: (1) cfDNA in saliva reflects cellular homeostasis and can exhibit cancer-specific DNA methylation patterns. (2) Exosomes in saliva interact with target cells and transfer their contents, playing a role in cell-to-cell communication and serving as potential biomarkers for diagnostics. (3) Metabolites in saliva produced during metabolism assist in understanding metabolic changes. (4) mRNA and miRNA in saliva show altered gene expression levels, indicating the presence of diseases and monitoring physiological states. (5) Cytokines in saliva contribute to tumor growth and metastasis, serving as indicators of inflammatory responses and cancer progression. (6) Proteins in saliva provide comprehensive information on the protein content in saliva, offering insights into mechanisms and identifying potential biomarkers. Components isolated from saliva and their biological functions: cfDNA and DNA methylation.