**2. Incidence of oral cancer**

Despite the development of modern treatment methods, no significant achievement was reported in the prognosis, survival and mortality of oral cancer. According to the GLOBOCAN 2018 project, there is 354,864 new cases and 177,382 deaths due to oral cancer worldwide [7]. Geographically speaking, oral cancer is highly prevalent in South and Southeast Asia (India, Pakistan, etc.), West, Middle and Eastern of Europe (France, Germany, Hungary, etc.), and Oceania [4, 8, 9]. It is important to notice that the incidence of oral cancer is high in transitioning countries, particularly in India [10]. The incidence rate for the male is higher than female, approximately 10:1 to 2:1 [5, 7]. It is noted that oral cancer patients are usually aged from 50 to 70 years. However, increasing numbers of oral cancer patients have been observed at younger age, possibly due to a distinct etiology and pathogenesis [11].

## **3. Pathology of oral cancer**

More than 90% of oral cancers are squamous cell carcinoma (SCC) arising from the mucosal epithelium, namely oral squamous cell carcinoma (OSCC). A majority of them are moderate to well-differentiated. According to the WHO 2017 classification, eight kinds of subtypes are identified, including basaloid squamous cell carcinoma, spindle cell squamous cell carcinoma, adenosquamous carcinoma, carcinoma cuniculatum, verrucous squamous cell carcinoma, lymphoepithelial carcinoma, papillary squamous cell carcinoma, and acantholytic squamous cell carcinoma [12]. Each different subtype indicates different outcome.

Furthermore, a variety of oral potentially malignant disorders (OPMDs) have been reported to increase the potential of developing into oral cancer. Generally speaking, the common OPMDs, including erythroplakia, leukoplakia, oral submucous fibrosis, oral lichen planus, et al., increase the risk of malignant transformation, and they also serve as premalignant indicators in clinical works [12, 13].
