Salivary Biopsy in Oral Squamous Cell Carcinoma using cytokines, epigenetics and enzymes as biomarkers for early diagnosis: A Narrative Review.

Abstract

Over 90% of oral malignant lesions are attributed to Oral squamous cell carcinoma [OSCC]. Most cases are usually diagnosed at much later stages, regardless of the easily approachable location of the lesion, further resulting in poor prognosis. Although microscopic tissue analysis and grading of dysplasia point at the severity of lesion present, they fail to estimate the disease outcome or the prognostic pathway, emphasizing the immediate need for accurate biomarkers for early intervention and identification, despite tissue biopsy and visual assessment remain the gold standard for cancer diagnosis.    However, for early screening and therapeutic monitoring, saliva presents as a conservative, easily collected and repeatable specimen. Discharged through the vascularized salivary gland capillaries via systemic transudation or mucosal excretion, saliva consist of inflammatory cytokines, tumor-derived cell-free DNA [cfDNA], circulating tumor DNA [ctDNA], mRNA and various proteins making it a vital diagnostic tool.  This narrative review outlines screened salivary biomarkers including the inflammation-associated cytokines [Interleukin-6(IL-6),Interleukin-8(IL-8),TumorNecrosisFactor-α(TNF-α)] which are directly linked with tumor growth and further metastasis,stabilized exosome-encapsulated microRNAs [miR-21, miR-31, miR-184] and proteomic/enzymatic indicators [Lactate Dehydrogenase (LDH) Matrix Metalloproteinase-9 (MMP-9)] further demonstrating Warburg-driven metabolic shifts and basement membrane degradation, resulting in greater diagnostic sensitivity. However, clinical implementation of a multi-biomarker panel faces rational and operational impediments like metabolic shift in sample due to collection techniques, diet, oral hygiene, smoking and delay in sample processing. Hence, calibration of protocols for sample collection, processing and storage is of utmost importance to ensure replicability. To ensure quick, cellular and affordable testing point-of-care frameworks like the lab-on-a-chip technology, lateral flow immunoassay [LFIA] test strips or the microfluidic systems, offer a promising setting for early screening with low resource requirements eliminating the need for sophisticated laboratory network, further resulting in  timely medical decisions and increase in optimal patient care.