Abstract

Oral leukoplakia presents as a white patch on the oral mucosa and is recognized as having significant malignant potential. Although colonization of these patches with Candida albicans is common, little is known about the bacterial microbiota of these patches. In the current study we analyzed the microbiome of oral leukoplakia in 36 patients compared to healthy mucosal tissue from the same patients and healthy control subjects to determine if specific microbial enrichments could be identified early in the malignant process that could play a role in the progression of the disease. This was carried out by sequence analysis of the V1–V2 region of the bacterial 16S rRNA gene using the Illumina MiSeq. Oral leukoplakia exhibited increased abundance of Fusobacteria and reduced levels of Firmicutes (Metastats P < 0.01). Candida colonization was also more prevalent in leukoplakia patients relative to healthy controls (P = 0.025). Bacterial colonization patterns on oral leukoplakia were highly variable and five distinct bacterial clusters were discerned. These clusters exhibited co-occurrence of Fusobacterium, Leptotrichia, and Campylobacter species (Pearson P < 0.01), which is strikingly similar to the microbial co-occurrence patterns observed on colorectal cancers (Warren et al., 2013). Increased abundance of the acetaldehydogenic microorganism Rothia mucilaginosa was also apparent on oral leukoplakias from lingual sites (P 0.0012). Severe dysplasia was associated with elevated levels of Leptotrichia spp. and Campylobacter concisus (P < 0.05). Oral leukoplakia exhibits an altered microbiota that has similarities to the microbiome of colorectal cancer.

Highlights

  • Oral squamous cell carcinoma is the most common oral malignancy and is the eight most common cancer worldwide (Scully and Bagan, 2009)

  • Malignant transformation of oral leukoplakia (OLK) is greater with increasing age, female gender, non-smoking, extent of OLK and may be affected by location, with some studies reporting that OLK on the lateral and ventral surfaces of the tongue and the floor of mouth having a higher rate of transformation (Silverman et al, 1984; Ho et al, 2012; Liu et al, 2012; Yanik et al, 2015)

  • Our study identifies a specific enrichment in Fusobacteria and Campylobacter spp. that bears similarity to recently identified enrichments on colorectal carcinoma

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Summary

Introduction

Oral squamous cell carcinoma is the most common oral malignancy and is the eight most common cancer worldwide (Scully and Bagan, 2009). Failure to diagnose in the early stages of tumor development can have a dramatic impact upon long-term prognosis, with 5 year survival of late stage OSCC being less than 40% (Yanik et al, 2015). Malignant transformation of OLK is greater with increasing age, female gender, non-smoking, extent of OLK and may be affected by location, with some studies reporting that OLK on the lateral and ventral surfaces of the tongue and the floor of mouth having a higher rate of transformation (Silverman et al, 1984; Ho et al, 2012; Liu et al, 2012; Yanik et al, 2015). The degree of dysplasia is at present the most reliable indicator of the likelihood of transformation (Scully and Bagan, 2009; Liu et al, 2012)

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