The relationship between C. albicans and the etiology of OLP has long been puzzling many researchers and it still remains to be elucidated. The present study revealed that C. albicans from OLP were quantitatively and qualitatively distinctive with heathy individuals. Moreover, C. albicans isolates from both NE-OLP and E-OLP were genetically distinguishable from those in control group. These suggest that OLP might be a predisposing condition to Candida infection and certain specific genotypes of C. albicans are probably involved in occurrence and progression of OLP.
Generally, the prevalence of C. albicans in OLP patients differs from that found in healthy individuals. It has been reported that a positive Candida culture is more prevalent among OLP patients (48.9%) than among control subjects (26.7%) . In the present study, we also identified a definitely higher positive frequency of C. albicans in the NE-OLP group and E-OLP group compared to healthy individuals. This discrepancy might cause the dysfunction of lymphocytes in OLP. As Simark-Mattsson et al showed the proliferation and cytokines production of peripheral blood mononuclear cells from OLP were significantly reduced following the stimulation of C. albicans, thus reflecting a potential immune regulatory mechanism of OLP modulating by C. albicans . The high prevalence of specific C. albicans isolates in OLP suggest that they might potentially have strong adaptability to the microenvironment under the dynamic interaction between OLP progression and the fungal strains . Yet, this is not consistent with results reported by Artico et al, who found that the positive prevalence of colonization by Candida spp. was higher in healthy subjects than in OLP . The possible explanation for this discrepancy may lie in the differences of the sample size and methods including sample collection sites.
In the present study, the RAPD and ITS sequences were both chosen, because other studies failed to further classify C. albicans among different groups situation, with no better precision than telling just that they were C. albicans, and above reported two methods’ results had a clear coherence and consistency. In fact, it is a well-known fact that phenotyping is vulnerable to being influenced by environment and involved in poor repeatability, weak identification, and instability . In contrast, genotyping improves the precision of C. albicans species and subtypes . What supports the importance of genotyping is that C. albicans does not differ in phenotype between dimorphologicly respective symbiotic and pathogenic situations.
Although other technologies as multilocus sequence typing and microsatellite typing are thought to be more efficient and reliable, and even if the RAPD and ITS-PCR are viewed as obsolete by some scholars, we found them to be very useful. As a result, RAPD products showed by electrophoresis analysis that the healthy controls had only one band, E-OLP isolates had multiple bands, and all the eight NE-OLP isolates focused on two bands, and were further confirmed by ITS sequence. Moreover, the genetic homology coefficient SAB was less than 30% between the control, NE-OLP, and E-OLP groups, while it was 100% inside subgroup. Previous genotyping results have usually revealed that C. albicans infection in OLP are exogenous , while authors here think that if they were exogenous, they should be disordered or similar in E-OLP or NE-OLP instead of the ordered genotypes. In addition, the exogenous colonization of C. albicans should reveal some indefiniteness and randomness. Nonetheless, a common natural symbionts C. albicans in OLP has not yet been found, which is why we are more inclined toward our initial hypothesis. On the contrary, we assumed that it was the endogenous genotypic changes of oral C. albicans under special environmental and ecological conditions that led to development of OLP. This might be because the specific microenvironment fostered a mutation of C. albicans from symbionts to further specific pathogenic genotypes which is also supported by other researches [16,23,24] and hopefully future molecular epidemiology, and to induce a T-cell-mediated immune response. As for elements of microenvironmental oral cavity including PH, temperature and ingredients in salivary or gum fluids, they have been identified to induce pathogen’s virulence key gene mutation and immune reaction or new balance . Also, it is possible that the mutation drives C. albicans to get involve in and better adapt to a current environment , thus forming the type of dominant pathogen, which eventually affects the severity of the disease upon its interaction with the host. In this study, the results of both RAPD and ITS sequence showed that both intra-species homology and inter-species variations existed in C. albicans among the three clinical groups. The correlation between pathogen mutation and clinical progression of OLP was reflected in the changes from type I for normal strains, to type IIa, type IIb for NE-OLP, and to type III for E-OLP strains. Besides the underlying implication that an endogenous mutation of Candida might be the key to uncovering the etiology of OLP, these finidngs can potentially be used as indicator for the severity evaluation for OLP, as well as a therapeutic basis for individualized treatment.
Although previous studies have reported that OLP attracts C. albicans’ collection in lesions , we assume that Candida is probably the initial pathogen and the antigen for OLP (Figure 6), since that OLP can be easily cured by addressing oral hygiene and dental health problems, which quite often involve fungi. If not so, solving the oral hygiene, dental and oral health, consuming antifungal drugs should have never worked. From these clinical aspects, the curative effect is comparatively easier in treating E-OLP than NE-OLP with superficial consumption of corticosteroids, and then subsequently or simultaneously addressing dental and hygiene problems same as treating NE-OLP. Correspondingly, overlooked patients’ poor oral hygiene and health habits are indeed the cause for substantially prolonged healing and recurrences of OLP showing in our daily work and also mentioned in other studies . In fact, practice experience tells us that addressing oral hygiene and dental problems (which tend to involve numerous fungi and Candida) is a most effective way to cure OLP in clinical work with more accuracy than other therapies such as adoption of immune drugs or herb products and similar medicine.
Accordingly, a strong positive relationship has also been identified between the Candida infection in oral cavity and the degree of epithelial dysplasia or OSCC [3, 29]. Gainza-Cirauqui and colleagues suggested that C. albicans isolated from potentially carcinogenic oral diseases could produce mutagenic amounts of acetaldehyde, which are involved in abnormal epithelial proliferation of mucosa . This further induced adverse events like disorders and formation of strange cellular keratin that deteriorates the abnormal nuclear divisions and cell proliferation in epithelial plaque, thus developing to cancers . Therefore, clinicians should pay special attention to the presence of Candida altering from combionts to pathogenic, and any premalignant dental-to-mucosa friction injury when treating patients with OLP and OLP with epithelial dysplasia or carcinoma.
Our results with the clinical C. albicans strains confirmed that the ITS sequences and RAPD homology coefficient SAB of C. albicans were obviously different among E-OLP, NE-OLP and healthy individuals, thus suggesting that endogenous C. albicans in oral environment may be involved in the etiology and pathogenesis of OLP. Although the sample of strains in this study was small, and the mutual effect between OLP lesion and C. albicans gene mutation is dynamic and complex, reported results are strong. Nonetheless, future studies with larger sample size or an OLP animal model are required to further verify reported findings.