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 KimDavid Sidransky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)110931-110948
Number of pages18
JournalOncotarget
Volume8
Issue number67
DOIs
StatePublished - Jan 1 2017

Keywords

  • High-resolution microbiome profiling
  • Human microbiome project
  • Microbiota
  • Oral cancer
  • Oropharyngeal cancer

ASJC Scopus subject areas

  • Oncology

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    Guerrero-Preston, R., White, J. R., Godoy-Vitorino, F., Rodríguez-Hilario, A., Navarro, K., González, H., Michailidi, C., Jedlicka, A., Canapp, S., Bondy, J., Dziedzic, A., Lagos, B. M., Rivera-Alvarez, G., Ili-Gangas, C., Brebi-Mieville, P., Westra, W., Koch, W., Kang, H., Marchionni, L., ... Sidransky, D. (2017). 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. Oncotarget, 8(67), 110931-110948. https://doi.org/10.18632/oncotarget.20677