Research Papers:

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

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Oncotarget. 2017; 8:110931-110948. https://doi.org/10.18632/oncotarget.20677

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Rafael Guerrero-Preston1,2, James Robert White3, Filipa Godoy-Vitorino4, Arnold Rodríguez-Hilario4, Kelvin Navarro4, Herminio González4, Christina Michailidi1, Anne Jedlicka5, Sierra Canapp1, Jessica Bondy1, Amanda Dziedzic5, Barbara Mora-Lagos1,6, Gustavo Rivera-Alvarez1,2, Carmen Ili-Gangas6,7, Priscilla Brebi-Mieville6,7, William Westra1, Wayne Koch1, Hyunseok Kang8, Luigi Marchionni8, Young Kim9 and David Sidransky1

1Department of Otolaryngology and Head and Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA

2Department of Obstetrics and Gynecology, University of Puerto Rico, School of Medicine, San Juan, Puerto Rico

3Department of Computational Biology Resphera Biosciences, Baltimore, MD, USA

4Natural Sciences Department, Microbial Ecology and Genomics Lab, Inter American University of Puerto Rico, Metropolitan Campus, San Juan, Puerto Rico

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, School of Public Health, Baltimore, Maryland, USA

6Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile

7Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile

8Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA

9Department of Otolaryngology, Vanderbilt University School of Medicine, Nashville, TN, USA

Correspondence to:

Rafael Guerrero-Preston, email: rafael.guerrero@upr.edu

David Sidransky, email: dsidrans@jhmi.edu

Keywords: microbiota, high-resolution microbiome profiling, oral cancer, oropharyngeal cancer, human microbiome project

Received: April 27, 2017     Accepted: July 12, 2017     Published: September 07, 2017


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.

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