Saliva Based Liquid Biopsies in Head and Neck Cancer: How Far Are We From the Clinic?

Abstract

Head and neck cancer (HNC) remains to be a major cause of mortality worldwide because of confounding factors such as late-stage tumor diagnosis, loco-regional aggressiveness and distant metastasis. The current standardized diagnostic regime for HNC is tissue biopsy which fails to determine the thorough tumor dynamics. Therefore, due to the ease of collection, recent studies have focused on the utility of saliva based liquid biopsy approach for serial sampling, early diagnosis, prognosis, longitudinal monitoring of disease progression and treatment response in HNC patients. Saliva collection is convenient, non-invasive, and pain-free and offers repetitive sampling along with real time monitoring of the disease. Moreover, the detection, isolation and analysis of tumor-derived components such as Circulating Tumor Nucleic Acids (CTNAs), Extracellular Vesicles (EVs), Circulating Tumor Cells (CTCs) and metabolites from saliva can be used for genomic and proteomic examination of HNC patients. Although, these circulatory biomarkers have a wide range of applications in clinical settings, no validated data has yet been established for their usage in clinical practice for HNC. Improvements in isolation and detection technologies and next-generation sequencing analysis have resolved many technological hurdles, allowing a wide range of saliva based liquid biopsy application in clinical backgrounds. Thus, in this review, we discussed the rationality of saliva as plausible biofluid and clinical sample for diagnosis, prognosis and therapeutics of HNC. We have described the molecular components of saliva that could mirror the disease status, recent outcomes of salivaomics associated with HNC and current technologies which have the potential to improve the clinical value of saliva in HNC.

Keywords: biomarker; circulating tumor nucleic acids; extracellular vesicles; head and neck cancer; liquid biopsy; metabolomics; saliva.

Figure 1

Summary of salivary components that can potentially act as biomarkers for HNC. This figure summarizes the current landscape of salivary components that may act as biomarkers for HNC. The detection and analysis techniques and clinical applications for each component are mentioned in the figure. (NMR: Nuclear Magnetic Resonance, MS: Mass Spectrometry, HNC: Head and Neck Cancer, ddPCR: Droplet Digital Polymerase Chain Reaction, qPCR: quantitative Polymerase Chain Reaction, NGS: Next Generation Sequencing, SEC: Size-Exclusion Chromatography, NTA: Nanoparticle Tracking Analysis).