Oral cancer being a malignant neoplasm originates from the mucosa of the oral cavity and consists of a heterogeneous population of cells with varying biological characters. Oral cancer starts as a small, unfamiliar, unexplained growth in the oral cavity which includes lips, cheeks, tongue, hard and soft palate, floor of the mouth sometime extending into the pharynx.  Approximately 300,000 new cases and 145,000 deaths are registered in 2012, and is the 4th most prevalent cancer in the world. According to data from Global Cancer Observatory (GCO), there were 377,713 cases of OSCC worldwide in 2020, with the majority occurring in Asia. According to Globocan, in India alone the number of newly diagnosed cases of in 2022 were 1,98,438. Despite consistent gains in overall survival rates for patients with oral cancer, the early detection remains a problem for oral health care providers and five-year survival rate is still considered low.

Most cases of oral cancer are habit associated (tobacco/areca nut) and are preceded by asymptomatic clinical lesions collectively called as oral potentially malignant disorder (OPMD). OPMDs include leukoplakia, oral submucous fibrosis, erythroplakia, erosive lichen planus etc. The varied appearance, clinical presentation and signs and symptoms makes diagnosis difficult.  The prevalence rate of OPMDs varies from 1% to 5%. Early epidemiological studies in India investigating the risk of OPMDs found that 80% of oral cancers were influenced by OPMDs.

Oral submucous fibrosis (OSMF), a commonly occurring oral potentially malignant disorder (OPMD) has severe morbidity. World Health organization (WHO) Collaborating Centre for Oral Cancer in March 2020 defined OSMF as “a chronic, insidious disease that affects the oral mucosa, initially resulting in loss of fibro elasticity of the lamina propria and as the disease advances, results in fibrosis of the lamina propria and the submucosa of the oral cavity along with epithelial atrophy”. It is a multifactorial disease with areca nut being the main etiological agent. Contributory factors like smokeless tobacco, chilies, nutritional impairments, genetics, autoimmunity, and infections have been hypothesized. It occurs at any age group but is predominantly seen in adolescents and adults with age ranging from 16 to 35 years. The prevalence rate of OSMF varies from 0.2% to 0.5%. Unlike other OPMDs, OSMF is not reversible at any stage of the disease process and may become stationary or more severe even after cessation of the habit, making it a serious health concern causing both physical and psychological impact on the patient. The malignant transformation rate of OSMF is thought to range from 7 to 13%. Biopsy is considered as a gold standard for diagnosis of OPMDs and OSCC, it is not a preferred method for screening and follow-up due to its invasive nature, high cost, and requirement of trained medical personnel. Besides, the current diagnostic tools are not enough for detecting high risk OPMDs, as DNA mutations have been observed in epithelial cells with no evidence on histopathology. Thus, it becomes important to develop newer and non-invasive diagnostic tools for detection. Therefore the ‘liquid biopsy approach’ that focuses on detecting tumor- derived components/ biomarkers in body fluids for the diagnosis, screening and prognosis of cancer is becoming increasingly important.