Abstract

ABSTRACT Objective: While some oral carcinomas appear to arise de novo, others develop within long-standing conditions of the oral cavity that have malignant potential, now known as oral potentially malignant disorders (OPMDs). The oral bacteriome associated with OPMD has been studied to a lesser extent than that associated with oral cancer. To characterize the association in detail we compared the bacteriome in whole mouth fluid (WMF) in patients with oral leukoplakia, oral cancer and healthy controls. Methods: WMF bacteriome from 20 leukoplakia patients, 31 patients with oral cancer and 23 healthy controls were profiled using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and taxonomical classification was performed using the phylogenetic placement method. Sparse Partial Least Squares Regression Discriminant Analysis model was used to identify bacterial taxa that best discriminate the studied groups. Results: We found considerable overlap between the WMF bacteriome of leukoplakia and oral cancer while a clearer separation between healthy controls and the former two disorders was observed. Specifically, the separation was attributed to 14 taxa belonging to the genera Megaspheara, unclassified enterobacteria, Prevotella, Porphyromonas, Rothia and Salmonella, Streptococcus, and Fusobacterium. The most discriminative bacterial genera between leukoplakia and oral cancer were Megasphaera, unclassified Enterobacteriae, Salmonella and Prevotella. Conclusion: Oral bacteria may play a role in the early stages of oral carcinogenesis as a dysbiotic bacteriome is associated with oral leukoplakia and this resembles that of oral cancer more than healthy controls. Our findings may have implications for developing oral cancer prevention strategies targeting early microbial drivers of oral carcinogenesis.

Highlights

  • Oral potentially malignant disorders (OPMD) include conditions which harbour an increased risk of transfor­ mation to oral cancer when compared to patients with an apparently normal oral mucosa

  • A Sparse Partial Least Squares Regression Discriminant Analysis model was built using a subset of bacterial taxa that best discriminated the studied groups

  • This model demonstrated a considerable overlap between the LKP and cancer group (CA) group whereas the majority of healthy controls were separated from both these groups on component 1 (Figure 2)

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Summary

Introduction

Oral potentially malignant disorders (OPMD) include conditions which harbour an increased risk of transfor­ mation to oral cancer when compared to patients with an apparently normal oral mucosa. The rates of malignant transformation of LKP vary accord­ ing to the population as well as histopathologic grades of dysplasia historically categorized into mild, moder­ ate, and severe [1,2]. Histopathologic grading of dyspla­ sia remains the most useful predictor of the malignant transformation potential of LKP [3]. Over the years, researchers have explored various methods in the hope of develop­ ing sensitive and specific biomarkers for early detection of oral cancer or recognition of an OPMD with a relatively high likelihood of malignant transforma­ tion. No single marker has yet been shown to have sufficient utility to successfully translate to the clinical setting [4]

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