Is Candida albicans a promoting factor, rather than an inducing factor for oral cancer?

Xu Wang; Xinming Zhang; Shuangshuang Wu; Wenqing Zhang; Zhimin Yan

doi:10.1080/20002297.2025.2564694

Is Candida albicans a promoting factor, rather than an inducing factor for oral cancer?

J Oral Microbiol. 2025 Sep 29;17(1):2564694. doi: 10.1080/20002297.2025.2564694. eCollection 2025.

Authors

Xu Wang^{1

2

3}, Xinming Zhang^{1

2

3}, Shuangshuang Wu^{1

2}, Wenqing Zhang^{1

2}, Zhimin Yan^{1

2}

Affiliations

¹ Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China.
² National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
³ Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.

Abstract

Background: Candida albicans (C. albicans) is closely associated with cancer. Whether C. albicanscan directly induce the occurrence of oral cancer remains undetermined.

Objective: This study aimed to explore the carcinogenic potential of C. albicans in oral cancer.

Methods: Transcriptome sequencing (mRNAseq) and whole exome sequencing (WES) were performed to reveal the effects of long-term C. albicans stimulation on oral mucosa in mouse models. 4-nitroquinoline-1-oxide (4NQO), a mutagenic substance that mimics tobacco, was used to examine the combined role of tobacco smoking and C. albicans in oral carcinogenesis. Additionally, the somatic mutation landscape of chronic hyperplastic candidiasis (CHC)-a variant of oral candidiasis typically presenting with dysplasia-was characterized in biopsy tissues.

Results: Long-term C. albicans stimulation didn't directly induce oral cancer in mouse models but significantly upregulated the expression of genes related to cell proliferation and cancer development in the oral epithelium (e.g. Mki67, Kif11, Ccna2, Ckap2, Fos, Ccnb1; P < 0.05). Analysis of somatic mutations in CHC revealed that Candida and smoking might co-contribute to this type of precancerous lesion. Furthermore, C. albicans stimulation activated signaling pathways involved in inflammation and immune response, and promoted cancer formation in mice pre-treated with 4NQO.

Conclusion: C. albicans alone rarely induces carcinogenesis directly but can accelerate the malignant transformation of oral mucosa when combined with smoking.

Keywords: Candida albicans; genotoxicity; inflammation; oral cancer; somatic mutation.

Plain language summary

C. albicans didn't directly induce the occurrence of oral cancer in the absence of other cancer risk factors.Chronic hyperplastic candidiasis exhibited single base substitution signatures similar to SBS5.C. albicans promoted oral carcinogenesis in mice pre-treated with chemical stimulation.