Abstract

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence.

Highlights

  • 22,000 Americans are diagnosed with oral cancer of which 90% are squamous cell carcinoma (SCC)

  • To investigate changes in the oral microbiome associated with oral cancer, we prospectively collected cancer and anatomically matched patient clinically normal samples from five patients (Table 1, Study 1 Discovery Cohort, Table S1)

  • Considering cancer/normal paired samples, we identified 11 Operational Taxonomic Unit (OTU) from the phyla Actinobacteria (Actinomyces and Rothia, 2 OTUs from each genus) and Firmicutes (Streptococcus, 7 OTUs) that were significantly decreased in cancers and one OTU from the phylum Fusobacteria (Fusobacterium) that was increased in cancers compared to anatomically matched contralateral normal patient samples (Table S17)

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Summary

Introduction

22,000 Americans are diagnosed with oral cancer of which 90% are squamous cell carcinoma (SCC). The five-year survival, at 40% has not improved in the past 40 years, and it is one of the lowest of the major cancer sites, resulting in more people dying from oral cancer than melanoma, cervical or ovarian cancer in the USA. The major risk factors, tobacco and alcohol use, cannot explain the changes in incidence, because oral cancer commonly occurs in patients without a history of tobacco or alcohol exposure [3]. Human papillomavirus (HPV) has been identified as an etiologic agent for oropharyngeal cancer, but HPV infection is not a significant contributor to oral cancer, as the virus is rarely found in these cancers (2–4% of cases) [4]. Contributions from other, possibly environmental factors remain to be found

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