## 1 Introduction  
Oral squamous cell carcinoma (OSCC) is a multifactorial disease, with tobacco and alcohol being the most common independent risk factors [1; 2; 3; 4; 5]. Apart from these known risk factors, several factors (microbiome; lifestyle factors including obesity, diet, and occupation; environmental factors like air pollution, heavy metal exposure, and genetic susceptibility) have been implicated in the development of OSCC [6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29], although their evidence of association is limited. Thus, such factors are termed potential risk factors. One such factor for OSCC is microorganisms. Studies have shown the presence of several oral microbes in OSCC patients [6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20]. Unlike external factors like tobacco and alcohol, the presence of oral microbes in an OSCC case could be a result of the microbe being a commensal or a secondary infection in the cancerous tissue. Thus, eliciting the role of microorganisms in OSCC would first require the establishment of a significantly higher association of the microbe in OSCC compared to healthy patients with normal oral mucosa. If a significant association is noted in OSCC, then the microbe in question can be assessed for the presence of carcinogenic properties. Among oral microbes, much importance has been given to human papillomavirus (HPV) types 16 and 18, due to their proven association with cervical and orophangel cancer [30; 31; 32]. On the contrary, the role of HPV in OSCC remains inconclusive due to discrepancies in the results of individual studies [6]. Similar to HPV, microbes implicated in cancer in other anatomical locations including Helicobacter pylori in gastric cancer, have been assessed for its association with OSCC [33]. In most cases, the studies have been inconclusive, which is largely attributed to the differences in the sensitivity and specificity of the diagnostic modalities used to detect the microbes. In addition, if the oral microbe in question is present in a higher proportion as a commensal in the control (healthy individuals with normal oral mucosa) population, the results of the comparison between OSCC and the control often turn to insignificant or in few studies, even an inverse correlation has been recorded [20]. Due to these limitations, analyzing the association between oral microbes and OSCC has been largely inconclusive. One of the most commonly studied oral microbes in OSCC is _Candida_[16; 17; 18; 19; 34; 35; 36; 37; 38; 39; 40]. _Candida albicans_ have shown to produce carcinogens including nitrosamines, which can activate proto-oncogenes triggering carcinomas changes [41]. _Candida_ is also capable of breaking down ethanol in to acetaldehyde, which in turn can cause adducts in protein and DNA [42; 43; 44; 45]. These DNA adducts have shown to interfere with DNA replication resulting in point mutations, and aberrations of the chromosome [46]. Acetaldehyde has also shown to affect the cytosine methylation and DNA repair enzyme causing cell cycle aberrations which may culminate in tumor development [47]. In addition, acetaldehyde can increase the reactive oxygen species by binding with anti-oxidative peptide glutathione increasing the risk of DNA damage. The mitochondrial damages induced by the acetaldehyde have also shown to increase the reactive oxygen species, and key survival factors including NF-kb, which can in turn increase the risk of tumour development [48; 49]. The acetaldehyde level considered to be carcinogenic is 4100 uM [43]. Among the _Candida_ aspecies, _Candida albicans_ (CA) and a few non-_Candida albicans_ (NCA) _including Candida parapsilosis_ and _Candida tropicalis_ have shown to exceed this threshold level [41]. Despite multiple observational studies being published on the prevalence and species specificity of _Candida_ in OSCC, the association of _Candida_ with OSCC remains to be inconclusive, which again is due to the same limitations as suggested for _H. pylori_ and HPV based studies.