Abstract
Oral squamous cell carcinoma (OSCC) has a multifactorial aetiology. The advanced disease is associated with significant morbidity and mortality. Many OSCC are preceded by clinically apparent oral potentially malignant disorders (OPMD) providing a potential window for early diagnosis and intervention to achieve better clinical outcomes. Candida albicans is a common oral commensal but may turn pathogenic under certain conditions. An association between C. albicans and OPMD/OSCC has been claimed since the 1960s. Yet, there is no convincing evidence to incriminate the organism with a causative role in oral carcinogenesis.
Aim of the study: To investigate the role of C. albicans colonization and infection in oral carcinogenesis using immunohistochemistry (IHC), histopathology and clinical information in patients with OPMD/OSCC.
Study hypothesis: Presence of C. albicans colonization and infection will show a positive correlation with severity of oral epithelial dysplasia (OED) and expression of specific molecular markers when compared with lesions without the presence of C. albicans.
Materials and methods: The study sample comprised formalin-fixed paraffin-embedded (FFPE) oral mucosal biopsy tissues of consecutive patients who presented for treatment of clinically suspicious OPMD/OSCC at a referral hospital in Sri Lanka. Clinical data collected included demographic, behavioural and health related information. The presence/absence of lesion surface colonization by C. albicans was determined by culturing material obtained from a scraping. Subsequently all lesions were biopsied and histopathologically examined to detect and record the presence/absence of Candida hyphae infiltration in the epithelium and for the presence/absence of low-risk OED, high-risk OED or OSCC. Clinical information was tabulated and statistically analysed to investigate whether presence/absence of C. albicans colonization was an independent risk factor for presence/absence of high-risk OED/OSCC. Immunohistochemistry was performed to assess p53 and Ki67 protein expression in 62 selected samples with either, C. albicans colonization and infection or without C. albicans colonization/infection.
Results: The study sample (n=139) comprised 127 males (mean age 57.4 yrs.) and 12 females (mean age 63.6 yrs.). Betel-quid chewing was common (58.3%) followed by alcohol use (46.8%) and smoking tobacco (29.5%). Only 12.9% were denture wearers while 28.1% reported a medical condition indicative of potential immune compromise. Ninety-six (69.1%) patients had C. albicans colonization of which 28 (29.2%) showed Candida infection with hyphae invading the parakeratin layer of the epithelium. A highly significant independent association was observed between C. albicans colonization and OPMD having high-risk OED (p=0.00, RRR=4.92). Immunohistochemistry (n=62) showed marginally significant (p=0.08) increased mean immunoreactive score for anti-Ki67 in Candida-infected OPMD. There was significantly high immunopositivity for anti-Ki67 (p<0.01) and anti-p53 (p=0.01) evident in the maturation compartment of the epithelium in OPMD having Candida colonization and infection.
Conclusions: C. albicans colonization in oral mucosal lesions had a significant independent association with occurrence of high-risk OED and OSCC. The presence of C. albicans colonization and infection is associated with increased cell proliferation and a significantly increased immunopositivity for anti-Ki67 and anti-p53 in the maturation compartment of the epithelium on OPMD. Taken in context, these findings support a potential causative role for C. albicans in oral carcinogenesis which merits further investigation and validation.