Salivary Biomarkers in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma in the Indian Population: A Narrative Review

Abstract

Oral squamous cell carcinoma (OSCC) accounts for the great majority of oral malignancies and remains a major public health problem in India, where its incidence is disproportionately high relative to global figures. Five-year survival has stayed close to 50-62% for several decades [1,2], largely because most patients present only after the disease has reached an advanced stage. OSCC is usually preceded by a recognisable pre-malignant phase - oral potentially malignant disorders (OPMDs) such as leukoplakia, oral submucous fibrosis, erythroplakia, and lichen planus - whose annual rate of malignant transformation ranges from under 1% to as high as 17%, depending on lesion type. Tissue biopsy remains the diagnostic gold standard, but it is invasive, resource-intensive, and poorly suited to mass screening or repeated monitoring of the same lesion.

Saliva offers a non-invasive alternative that sits in direct contact with oral lesions and carries proteins, nucleic acids, and metabolites shed by tumour and pre-malignant tissue. This narrative review compiles the information related to salivary biomarkers for OPMDs and OSCC in Indians, considering both protein/chemical biomarkers, including interleukins, oxidative stress markers, and tumor-specific enzymes, as well as genomic/transcriptomic markers such as microRNAs, mRNA, and cell-free circulating DNA. The review highlights the Indian population’s unique risk factors—chewing smokeless tobacco and areca nuts/betel quid- along with their influence on the salivary milieu. Salivary IL-6 appears to be the best validated single biomarker, with sensitivity and specificity greater than 95% reported in various Indian populations. Other multi-marker and multi-omics approaches result in further advancements in detection capability. The review ends with an analysis of the drawbacks of existing literature, small cross-sectional design, inconsistency in methodology, and underrepresentation geographically—and defines the future directions for implementation of the biomarkers into practice in India...