Longitudinal Characterization of the Tumoral Microbiome during Radiotherapy in HPV-associated Oropharynx Cancer

Abstract

Purpose: To describe the baseline and serial tumor microbiome in HPV-associated oropharynx cancer (OPC) over the course of radiotherapy (RT). Methods: Patients with newly diagnosed HPV-associated OPC treated with definitive radiotherapy +/- concurrent chemotherapy were enrolled in this prospective study. Using 16S rRNA gene sequencing, dynamic changes in tumor microbiome during RT were investigated. Surface tumor samples were obtained before RT and at week 1, 3 and 5 of RT. Radiological primary tumor response at mid-treatment was categorized as complete (CR) or partial (PR). Results: Ten patients were enrolled. Mean age was 63 years (range: 51-71). As per AJCC 8th Ed, 50%, 20% and 30% of patients had stage I, II and III, respectively. At 4-weeks, 7 patients had CR and 3 patients had PR; at follow-up imaging post treatment, all patients had CR. Baseline diversity of tumoral and buccal microbiomes was not statistically different. For the entire cohort, alpha diversity was significantly decreased over the course of treatment (p=0.02). There was a significant alteration in the bacterial community within the first week of radiation. Baseline tumor alpha diversity of patients with CR was significantly higher than those with PR (p=0.03). While patients with CR had significant reduction in diversity over the course of radiation (p=0.02), the diversity remained unchanged in patients with PR. Patients with history of smoking had significantly increased abundance of Granulicatella (p=0.04), and Kingella (0.05) and lower abundance of Alloprevotella (p=0.04) compared to never smokers. Conclusions: The tumor microbiome of HPV-associated OPC exhibits reduced alpha diversity and altered taxa abundance over the course of radiotherapy. The baseline bacterial profiles of smokers vs. non-smokers were inherently different. Baseline tumor alpha diversity of patients with CR was higher than patients with PR, suggesting that the microbiome as a biomarker of radiation response deserves further investigation.

Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-Institutional Prospective Cohort Evaluation

“…The dynamic variation of the GM over the course of NAC in bladder cancer has not been studied, however, studies within colorectal[29], head and neck[30] and cervical cancer [31] [32]have all demonstrated significant fluctuations in composition. It is therefore not surprising, that the longitudinal microbiota fluctuations in our study are mostly driven by an increase in Bacteroides abundance during the course of chemotherapy.…”

The microbiota and radiotherapy for head and neck cancer: What should clinical oncologists know?

“…Schuurhuis et al followed a cohort of 26 and 27 oral or oropharyngeal cancer patients treated with radiotherapy and radiochemotherapy respectively and found that, when compared to patients treated with surgery alone, patients treated with radiotherapy had increased abundance of enteric rods, staphylococci and Candida one year after treatment [77]. Finally, another small study reported a shift in the composition of the bacterial community, with Actinomyces and Leptotrichia declining over the course of radiation, while Veillonella and Atopobium increased [36].…”

Distinct Microbial Communities Colonize Tonsillar Squamous Cell Carcinoma

“…Noteworthy, the majority of studies elaborating on the composition of the tonsillar microbiome have analyzed tissues from pediatric patients [14][15][16][17][18][19][20][21]. Tonsil cancer occurs only in adults and the few available datasets on the adult microbiome in tonsil cancer have not considered the inclusion of age-matched control cohorts [22,23]. Here, we have analyzed the tonsillar crypt microbiome from two different patient cohorts.…”