## 4 Discussion  
Under physiological conditions, \(CA\) is considered as one of the most common _Candida_ species in the oral cavity [51]. Thus, most studies on _Candida_ have largely focused on \(CA\). In a majority of these  
Figure 4: Forest plot summarizing the results of the meta-analysis for \(NCA\) and OSCC. Figure 3: Forest plot summarizing the results of the meta-analysis for CA and OSCC. _CA_-based studies, the experimental model includes the isolation and characterization of the _Candida_ from the oral cavity _through_ salivary sampling, oral rinse, or an oral swab [34; 35; 36; 37; 38; 39; 40]. Estimating the prevalence of _Candida_ and the species specificity for different population groups is a major research strategy employed in oral _Candida_-based studies. Despite being a commensal, _CA_ is a well-established opportunistic infection, capable of inducing both local and systemic infections [51]. Thus, research on the prevalence and species specificity of _Candida_, including _CA_, has been extended to a wide range of disease entities, especially with immunodeficiency states such as HIV/AIDS, and transplant patients wherein the opportunistic nature of _Candida_ have a higher risk of establishing an infection [52; 53; 54; 55]. Although common anti-fungal agents have shown to effective against _CA_, their efficiency is relatively poor against the _NCA_ due to their inherent treatment resistance and virulence properties [56; 57]. A shift in the _Candida_ flora from _CA to NCA_ has been suggested as a sign of oral dysbiosis which could potentially increase the risk of local and systemic diseases, including cancer [18; 19]. Several studies have evaluated the carcinogenic potential of _Candida_ through epidemiological, in vitro, and in vivo studies [34; 35; 36; 37; 38; 39; 40; 58; 59; 60; 61; 62; 63; 64]. Despite evidence of producing carcinogenic agents such as acetaldehyde [64], the evidence for a causal association between _Candida_ and OSCC has been largely inconclusive. The lack of evidence is in turn attributed to the varying epidemiological data from individual studies [34; 35; 36; 37; 38; 39; 40]. To overcome the limitation of individual study differences, the present literature review was formulated to provide a comprehensive estimate of _Candida_ prevalence and species specificity in OSCC through qualitative and quantitative analysis. The present systematic review included seven case-control observational studies [34; 35; 36; 37; 38; 39; 40] wherein the control were individuals with normal oral mucosa and the cases were histopathologically confirmed OSCC. Although each study had other variable groups ranging from smokers, oral leukoplakia (OL), oral potentially malignant disorder (OPMD), oral lichen planus (OLP), the review focused primarily on the results of the _Candida_ prevalence and species specificity in OSCC and the healthy controls. As mentioned earlier, the most common sampling techniques were oral swab, oral rinse, and saliva. Other than oral swab, the other sampling techniques could potentially include microbial colonies from different parts of the oral cavity and may not be a true representation of the lesional area. The most common diagnostic modality used was CHROMagar. Being a relatively economical modality compared to genotyping, the CHROMagar-based chromogenic differentiation is often the most desired system of _Candida_ species differentiation. The subjectivity of the observers in determining the color of the colonies in CHROMagar often leads to inter-observer bias, which is its major limitation. Thus, many studies employ additional tests to confirm the findings of the CHROMagar. Some of the additional diagnostic modalities used in the studies included in the present review are the germ tube test, API ID 32C, Bichro-Dubli Fumouze -latex agglutination tests, chlamdogore production in milk serum and in cornmeal broth +5% milk media/corn meal agar, colony morphology, sugar assimilation, and fermentation tests, morphology in maize agar, growth at 42 \({}^{\circ}\)C, and real-time PCR.