Abstract

Oral microbiota dysbiosis is associated with the occurrence and progression of oral cancer. To investigate the association between the microbiota and risk of oral squamous cell carcinoma (OSCC), we identified the microbial composition of paired tumor (TT)/normal paracancerous tissues (NPT) and saliva (TS) samples in OSCC patients through 16S rRNA gene sequencing. A total of 22 phyla, 321 genera, and 869 species were identified in the oral samples. Paired comparisons revealed significant differences between TT, NPT, and TS groups, with the genus Filifactor significantly enriched in TT. The phylum Actinobacteria; genus Veillonella; and species Granulicatella adiacens, Streptococcus sanguinis, and Veillonella rogosae were significantly enriched in NPT, while the phylum Bacteroidetes; genera Capnocytophaga, Haemophilus, and Prevotella; and seven species, including Capnocytophaga sp., Haemophilus sp., and Neisseria sp., were significantly enriched in TS. In TTs, the abundance of Prevotella intermedia was profoundly higher in the gingiva, while Capnocytophaga gingivalis and Rothia mucilaginosa were enriched in the lining mucosa and tongue. Increasing in abundance from the early tumor stage to the late stage, Solobacterium moorei in TT and Campylobacter sp. strain HMT 044 in TS were positively correlated with OSCC development, suggesting that bacteria were selected by different microenvironments. The correlation between 11 microbial species and 17 pathway abundances was revealed, indicating the potential function of low-abundance bacteria. Overall, our analysis revealed that multiple oral bacterial taxa are associated with a subsequent risk of OSCC and may be used as biomarkers for risk prediction and intervention in oral cancers.

Highlights

  • More than 447,000 new diagnoses of and nearly 228,000 deaths due to oral cancer are reported worldwide, over 90% of which can be attributed to squamous cell carcinoma (SCC) (Bray et al, 2018)

  • Beta diversity analysis revealed a significant difference among tumor tissues (TTs), normal paracancerous tissue (NPT), and tissues (NPT) and saliva (TS) samples, indicating that oral microbiota dysbiosis might be involved in the progression of oral squamous cell carcinoma (OSCC) (Figure 1)

  • The comparison analysis revealed that microbiota colonizing TT, NPT, and TS samples showed significant differences

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Summary

Introduction

More than 447,000 new diagnoses of and nearly 228,000 deaths due to oral cancer are reported worldwide, over 90% of which can be attributed to squamous cell carcinoma (SCC) (Bray et al, 2018). SCC is defined as an epithelial malignancy with poor prognosis that originates from the buccal mucosa, tongue, mouth floor, gingiva, and oropharynx, with a 5year relative survival rate of less than 65% (Siegel et al, 2020). Environmental triggers, such as tobacco, alcohol consumption, and betel quid chewing, along with human papillomavirus infection, identified in the oropharynx, are major risk factors for oral cancer. A typical example of a bacterial carcinogen is Helicobacter pylori, which is known to promote gastric cancer (Amieva and Peek, 2016). It has been suggested that the oral microbiota plays an important role in carcinogenesis by stimulating chronic inflammation, producing carcinogenic substances, or inhibiting cell apoptosis (Karpinski, 2019)

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