Transitions in oral and gut microbiome of HPV+ oropharyngeal squamous cell carcinoma following definitive chemoradiotherapy (ROMA LA-OPSCC study)

Br J Cancer. 2021 Apr;124(9):1543-1551. doi: 10.1038/s41416-020-01253-1. Epub 2021 Mar 10.

Abstract

Background: Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT).

Methods: Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and β-diversity.

Results: A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R2 = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use.

Conclusions: Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Carcinoma, Squamous Cell / virology
  • Chemoradiotherapy / adverse effects*
  • Female
  • Follow-Up Studies
  • Gastrointestinal Microbiome*
  • Humans
  • Male
  • Mouth Mucosa / drug effects
  • Mouth Mucosa / microbiology*
  • Mouth Mucosa / radiation effects
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / therapy*
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology
  • Prognosis
  • Prospective Studies
  • Saliva / drug effects
  • Saliva / microbiology*
  • Saliva / radiation effects