The emerging role of liquid biopsy in oral squamous cell carcinoma detection: advantages and challenges

ABSTRACT

Introduction

Oral Squamous Cell Carcinoma (OSCC), the sixth most widespread malignancy in the world, accounts for 90% of all cases of oral cancer. The primary risk factors are tobacco chewing, alcohol consumption, viral infection, and genetic modifications. OSCC has a high morbidity rate due to the lack of early diagnostic methods. Nowadays, liquid biopsy plays a vital role in the initial diagnosis of oral cancer. ctNAs extracted from saliva and serum/plasma offer meaningful insights into tumor genetics and dynamics. The interplay of these elements in saliva and serum/plasma showcases their significance in advancing noninvasive, effective OSCC detection and monitoring.

Areas covered

This review mainly focused on the role of liquid biopsy as an emerging point in the diagnosis and prognosis of OSCC and the current advancements and challenges associated with liquid biopsy.

Expert opinion

Liquid biopsy is regarded as a new, minimally invasive, real-time monitoring tool for cancer diagnosis and prognosis. Many biomolecules found in bodily fluids, including ctDNA, ctRNA, CTCs, and EVs, are significant biomarkers to identify cancer in its early stages. Despite these groundbreaking strides, challenges persist. Standardization of sample collection, isolation, processing, and detection methods is imperative for ensuring result reproducibility across diverse studies.

KEYWORDS:

• Oral squamous cell carcinoma (OSCC)
• liquid biopsy
• circulating tumor cells (CTCs), circulating tumor DNA (ctDNA)
• circulating RNA (ctRNA)
• circulating extracellular vesicles (ctEVs)
• diagnostic and prognostic value

Article highlights

• Liquid biopsy, as a noninvasive method, uses body fluids (such as saliva and serum/plasma) as a sample for the early tumor diagnosis, staging, and monitoring of the recurrence of malignancy.

• Circulating tumor cells (CTCs), circulating extracellular vesicles (ctEVs), and circulating nucleic acids are the major components of liquid biopsy.

• Tumor-specific epigenetic changes like aberrant DNA methylation, promoter hypermethylation, and genetic changes like mutations in ctDNA can discriminate cancerous tissue from non-cancerous tissue.

• The development of specialized biomarker panels (gene mutation, DNA methylation, ctRNA, and ctEVs) using liquid biopsy has demonstrated encouraging diagnostic and prognostic potential in Oral Squamous Cell Carcinoma (OSCC).

• There are several challenges associated with liquid biopsy, which limit its usage in clinical practices, like low sensitivity and specificity, no standard protocol for sample handling and analysis, and high cost.

• Epithelial Mesenchymal Transition (EMT) in CTCs is the main and foremost cause of CTC heterogeneity, hence making their detection challengeable in liquid biopsy samples.

Abbreviations

oral squamous cell carcinoma, OSCC; circulating tumor nucleic acids, ctNAs; circulating deoxy ribonucleic acid, ctDNA; circulating ribonucleic acid, ctRNA; circulating extracellular vesicles, ctEVs; human papilloma virus, HPV; oropharyngeal carcinoma, OPC; 5-methylcytosine, 5-mc; circulating tumor cells, CTCs; extracellular vesicles, EVs; oral potentially malignant disorder, OPMDs; epithelial cell adhesion molecules, EpCAM; cytokeratin, CK; red blood cells, RBCs; epidermal growth factor receptor, EGFR; head and neck squamous cell carcinoma, HNSCC; food and drug administration, FDA; real time-quantitative polymerase chain reaction, RT-qPCR; fluorescent in-situ hybridization, FISH; next-generation sequencing, NGS; epithelial mesenchymal transition, EMT; cell-free DNA, cfDNA; quantitative methylation-specific PCR, q-MSP; long non-coding RNA, lncRNA; untranslated region, UTR; droplet digital PCR, ddPCR; vascular endothelial growth factor, VEGF; overall survival, OS; disease free survival, DFS; transmission electron microscope, TEM; nano particle tracking analysis, NTA; transforming growth factor-β, TGF- β; cancer associated fibroblasts, CAFs; lymph node metastasis, LMN; tumor microenvironment, TME; salivary cell-free DNA, scfDNA; oral cancer, OC; ribonucleoprotein complex, RNPs; small non-coding RNAs, sncRNAs; surface-enhanced Raman spectroscopy, SERS; not determined, ND.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose

Author contributions

Conceptualization: M Sachan; Writing-original draft: Su Gupta; Review & Editing: Su Gupta, B Singh, R Abhishek, Sa Gupta, M Sachan

Additional information

Funding

This paper was not funded.