Altered Bacteria Abundance Is Associated With Outcomes in Head and Neck Squamous Cell Carcinoma

Abstract

Objective: To determine if microbiome differences exist in head and neck squamous cell carcinoma (HNSCC) based on high-risk pathologic features, smoking, and outcomes using The Cancer Microbiome Atlas (TCMA).

Study design: Database study.

Setting: Database review.

Methods: TCMA is a publicly available database containing curated, decontaminated microbial profiles for tumors from 1772 patients. The data were limited to microbiome profiles, survival, and clinicopathologic features for HNSCC patients. Phyloseq objects were created, low-read samples were removed, and differential abundance analysis (DAA) using Analysis of Compositions of Microbiomes with Bias Correction 2 (ANCOM-BC2) was performed. Statistical analysis was done in R (v4.3.1).

Results: One hundred fifty-six patients with HNSCC were included from TCMA with a mean age of 59 (std 13, min 19, and max 90), 72% male (n = 113), and 91% white (n = 140). Primary sites encompassed oral cavity (n = 106, 68%), oropharynx (n = 26, 17%), and larynx/hypopharynx (n = 24, 15%). For all HNSCC in TCMA, rates of lymphovascular invasion were 17% (n = 26), perineural invasion, 34% (n = 53), and microscopic or gross extranodal extension (ENE), 19% (n = 30). DAA revealed significant changes in bacterial genera based on high-risk pathologic features, smoking status, vital status, and disease-specific survival (DSS). Genera observed with ANCOM-BC2 include Scardovia, Alloscardovia, Lactobacillus, and Corynebacterium genera for vital status and DSS.

Conclusion: Changes in the relative abundance of select intratumoral bacterial genera are associated with adverse pathologic features, DSS, and vital status in HNSCC. Shifts in the microbiome need further investigation to determine if they can provide any mechanistic insight or predictive role.

Keywords: The Cancer Microbiome Atlas; disease‐specific survival; high‐risk pathologic features; intratumoral bacteria; microbiome; oral squamous cell carcinoma; overall survival; smoking.

Figure 1

Kaplan‐Meier survival curves of (A) disease‐specific survival (DSS), (B) DSS based on extranodal extension (ENE), and (C) DSS based on margin status for head and neck squamous cell carcinoma using The Cancer Microbiome Atlas (TCMA) database (n = 156).

Figure 2

Microbial diversity analysis for histologic grade (well‐differentiated [G1] vs poorly differentiated [G3]) in head and neck squamous cell carcinoma. (A) Alpha diversity and (B) beta diversity.

Figure 3

Diverging plots demonstrating changes in the relative abundance of bacteria in head and neck squamous cell carcinoma tumors comparing (A) extranodal extension (ENE), (B) lymphovascular invasion (LVI), (C) perineural invasion (PNI), and (D) histologic grade.

Figure 4

Diverging plot demonstrating changes in the relative abundance of bacteria based on smoking status in head and neck squamous cell carcinoma (HNSCC).

Figure 5

Diverging plots demonstrating changes in the relative abundance of bacteria based on vital status in (A) head and neck, (B) oral, (C) oropharyngeal, and (D) larynx/hypopharynx squamous cell carcinoma. Box plots demonstrating differences in select bacteria based on vital status in head and neck squamous cell carcinoma (HNSCC; E).

Figure 6

Diverging plot demonstrating changes in the relative abundance of bacteria based on disease‐specific survival (DSS) in head and neck squamous cell carcinoma (HNSCC).