High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation.

Rafael Guerrero-Preston,Carmen Ili-Gangas,Sierra Canapp,Anne Jedlicka,Gustavo Rivera-Alvarez,Priscilla Brebi-Mieville,Luigi Marchionni,Herminio González,Filipa Godoy-Vitorino,Young Kim,Amanda Dziedzic,David Sidransky,Hyunseok Kang,Jessica Bondy,Christina Michailidi,Kelvin Navarro,Arnold Rodríguez-Hilario,Wayne M Koch ,James R White ,William H Westra ,Bárbara Mora-Lagos

doi:10.18632/oncotarget.20677

Abstract

Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data.Resphera Insight applied to saliva samples from HNSCC patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva). These species were not observed in normal saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the Human Microbiome Project (HMP). Interestingly, both species were only observed in saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal cancer patients. We confirmed the representation of both species in HMP data obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples.Resphera Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages.Together, these high-resolution analyses on 583 samples suggest a possible role for bacterial species in the therapeutic outcome of HPV positive and HPV negative HNSCC patients.

Highlights

Microorganisms cause an estimated 20% of cancer in humans [1, 2]
Resphera Insight applied to saliva samples from head and neck squamous cell carcinoma (HNSCC) patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva)
Resphera Insight led to the discovery that Fusobacterium nucleatum, an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages

Summary

Introduction

Microorganisms cause an estimated 20% of cancer in humans [1, 2]. A handful of laboratories have reported links between the human microbiome, immuno modulators, inflammation and tumor initiation or progression in oral [6], colon [7,8,9,10], pancreatic [7, 11], liver [12], esophageal [13] and prostate cancers [14]. Cancer initiation and progression by oncogenic mutations, genomic instability, early tumor promotion, and enhanced angiogenesis are changes linked to chronic inflammation associated to multiple etiologies [20]. Tumor-associated inflammation enhances angiogenesis, promotes tumor progression and metastatic spread, and causes local immunosuppression [19]. Therapy-induced inflammation can enhance antigen presentation, leading to immunemediated tumor eradication [23]

Methods

Results

Conclusion