## 1 Introduction  
The International Agency for Research on Cancer of the World Health Organisation (IARC- WHO) has reported the alarming surge of cancer worldwide day by day [1]. According to the Global Cancer Observatory (GCO), the incidence of oral squamous cell carcinoma (OSCC) in 2020 was around 377,713 cases worldwide, with the highest cases in Asia (65.8%)followed by Europe (17.3%) and North America (7.3%), and the five-year prevalence was 959,248 cases, following the same regional trend. Even though the oral cavity has direct accessibility, early detection of cancer was mostly a failure: therefore, over the past few decades, the survival rates of oral cancer have remained unchanged. According to the GCO predictions, the incidence of OSCC is assumed to increase by up to 40% by 2040. Moreover, advances in molecular biology, genetics, diagnostics, and treatment regimens will lead to earlier diagnosis of cancer, improving mortality and morbidity rates [2]. OSCC represent 80-90% of all oral malignant neoplasm. The factors which are considered to be directly related to the high incidence of OSCC are smoking, betel quid, and tobacco chewing habits [3]. OSCC can develop de novo or as a result of pre-existing potentially malignant diseases [4]. Alteration in cell matrix interaction and cell signalling pathways can lead to increased biological aggressiveness of OSCC [5]. Genetic alterations result in the activation of proto-oncogenes and the inactivation of tumour suppressor genes by deletions, promoter methylation, point mutation, and gene amplification [6]. Genetic alteration causing progression of normal mucosa to cancer is shown in (Figure 1) More than 60 carcinogenic substances have been identified in tobacco smoke [7]. Tobacco contains Nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N\({}^{\prime}\)-Nitrosonornicotine which are also present in both smokeless and inhaled tobacco products. These are considered to be the prime etiologic factors [8]. Approximately 15% to 20% of all oral cancer cases have occurred in patients without the traditional risk factors, as seen in OSCC impacting non-smokers and non-drinkers [9]. One of the etiological factors in such cases is Human Papillomavirus (HPV). A staging design for high-risk HPV-associated cancer of the orophnx, different from the other etiological factors, was considered in the 8 th edition of the American Joint Committee on Cancer [10]. A variety of biological markers have been considered to diagnose and predict the prognosis of oral cancers and potentially malignant lesions. These markers can be divided into genomic markers that include DNA content (ploidy) chromosome aberrations, and changes in expression of oncogenes and tumour suppressor genes; proliferation markers; and differentiation markers that include keratans and carbohydrate antigens [11]. Oral carcinogenesis frequently includes alterations in proto-oncogenes and tumor suppressor genes such as p53, cyclin D1, EGFR, and p16. The mutant p53 protein accumulates in the cell, affecting its biological processes, and its overexpression is thought to be a leading indicator of poor prognosis [12]. The Epithelial Growth Factor Receptor (EGFR) is a cell cycle receptor that manages the cell cycle process and plays an integral part in tumour biology [13]. Cyclin D1 is a protein-encoding CCND1 gene that promotes the progression of the G1-S phase of the cell cycle. Overexpression EGFR and cyclin D1 is linked to a poor prognosis for the tumour [14]. The clinical outcome of the disease was found to be associated with the biological phenotypes of cancer. Better and more effective treatment modalities can be formulated if such biological characteristics can be identified [15]. A panel of IHC markers can be used for evaluating multiple prognostic molecular biomarkers that identify high-risk OSCC patients [16]. These markers include p53, cyclin D1, and EGFR. However, only a very few studies have been conducted so far in the literature, most of which have been conducted on breast and lung cancer.