Elsevier

Oral Oncology

Volume 51, Issue 2, February 2015, Pages 139-145
Oral Oncology

Oral Candida colonization in oral cancer patients and its relationship with traditional risk factors of oral cancer: A matched case-control study

https://doi.org/10.1016/j.oraloncology.2014.11.008Get rights and content

Summary

Objectives

Candida, an opportunistic fungal pathogen, has been implicated in oral and oesophageal cancers. This study aimed to examine oral Candida carriage in 52 oral cancer patients and 104 age-, gender- and denture status-matched oral cancer-free subjects.

Material and methods

We assessed general health, smoking and alcohol drinking habits, use of alcohol-containing mouthwash and periodontal status (community periodontal index of treatment needs). Yeasts were isolated using oral rinse technique and genetically identified via Real-Time PCR-High resolution melting curve analysis of conserved ribosomal DNA. Conditional and binary logistic regressions were used to identify explanatory variables that are risk factors for oral cancer.

Results and conclusion

The frequencies of oral yeasts’ presence and high oral colonization were significantly higher in oral cancer than non-oral cancer patients (p = 001; p = 0.033, respectively). No significant difference in the isolation profile of Candida species was found between the two groups, except C. parapsilosis was more frequent in non-oral cancer group. Differences were noticed in the incidence of C. albicans strains where significantly more C. albicans genotype-A was isolated from cancer patients and significantly more C. albicans genotype-B isolated from non-cancer patients. Multiple regression analyses showed significant association with cancer observed for alcohol drinking (OR = 4.253; 95% CI = 1.351, 13.386), Candida presence (OR = 3.242; 95% CI = 1.505, 6.984) and high oral colonization (OR = 3.587; 95% CI = 1.153, 11.162). These results indicate that there is a significant association between oral cancer occurrence and Candida oral colonization and that the observed genotypic diversity of C. albicans strains may play a role in oral carcinogenesis.

Introduction

Oral cancer, is the eighth most diagnosed cancer in Victorians in 2009 [1] and globally it ranks the 8th and the 13th most common malignancies for males and females, respectively [2]. The five-year survival rates are poor with 50% achieved only with optimal care [3]. Although the life quality for patients has been improved by surgical advances, overall mortality has not changed in the last 50 years [4]. Tobacco use and heavy alcohol consumption has been strongly associated with oral cancer [5]. Other postulated risk factors include poor oral hygiene [6], viral infections [7] and Candida albicans infections. Candida albicans has been associated with leukoplakic lesions and the presence of Candida species has been recognized as an independent risk factor for oral carcinoma [8].

Candida can cause a spectrum of oral mucosal lesions including chronic hyperplastic candidosis, (candidal leukoplakia). It has been postulated that this variant of oral candidosis carries a significant risk of malignant transformation [9], [10]. During the last four decades, increasing clinical and experimental evidence suggests a putative role for Candida in the multi-steps process of oral mucosal carcinogenesis. An aetiological role of Candida in causing progression to carcinoma was first suggested by Cawson in 1966 [11] with later reports suggesting a link between presence of C. albicans and oral squamous cell carcinoma [12], [13], [14], [15]. The most significant evidence is the increase in the frequency of C. albicans in biofilms from oral squamous cell carcinoma tumor sites compared to control areas [16] and the correlation between oral yeast carriage and the presence and degree of oral epithelial dysplastic and neoplastic changes [17].

To date there has not been a matched case-control study assessing all potential variables confounding oral cancer risk particularly regarding oral Candida colonization in oral cancer patients. Thus, this study aimed to firstly: isolate, identify and genotype oral yeasts from oral cancer patients and matched oral cancer-free subjects. Second, this study aimed to elucidate the association, if any, of oral Candida colonization with other known risk factors for oral cancer. We hypothesized that certain species, or strains, of Candida are associated with the presence of oral cancer and that Candida oral carriage and high level of colonization are risk factors in oral cancer.

Section snippets

Patient samples

Ethical approval was granted by the Human Research Ethics Committees of Melbourne Health (approval number 2012.133), Dental Health Services of Victoria (approval number 254) and Melbourne University (ethics ID 1238737). All patients gave informed consent prior to being enrolled in the present study. A total of 52 consecutive oral cancer patients and 104 age (±three years), gender and denture status (with or without denture) matched non-oral cancer control subjects were enrolled from October

Patients’ demographics

A total of 154 patients were enrolled in this study, 52 oral cancer patients (27 males and 25 females) and 104 non-oral cancer controls (54 males and 50 females). The median age was 61 years with a range of 23–88 years. The frequency of cancer sites in oral cancer patients (n = 52 patients) was: 18 (34.6%) tongue, 13 (25%) buccal mucosa, 11 (21.2%) floor of mouth, 5 (9.6%) retromolar area and 5 (9.6%) gingiva and labial mucosa.

No significant differences were found between oral cancer and non-oral

Discussion

The present study is the first matched case-control study to assess the diversity of Candida species and strains colonizing the oral cavity of oral cancer and non-oral cancer patients. In addition, it is the first comprehensive investigation of the association of oral Candida carriage and level of oral yeast colonization with oral cancer occurrence after a statistical adjustment of relevant risk factors such as tobacco smoking, alcohol drinking, medical problems (such as HPV and HIV

Conflict of Interest Statement

None declared.

Acknowledgement

This work was supported by Grant from Oral Health CRC (Cooperative Research Centre) of the Melbourne Dental School, The University of Melbourne.

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