Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma

• Published in: International journal of cancer 2023-05, Vol.152 (9), p.1903-1915
• Main Authors: Zhu, Hengyan, Yip, Hon Chi, Cheung, Man Kit, Chan, Hiu Ching, Ng, Cherrie, Lau, Eric H. L., Yeung, Zenon W. C., Wong, Eddy W. Y., Leung, Leanne, Qu, Xinyu, Wang, Daijuanru, Cai, Liuyang, Chan, Paul K. S., Chan, Jason Y. K., Chen, Zigui
• Format: Article
• Language: English
• Subjects: 16S rRNA; Bacteria - genetics; Cancer; Carcinoma, Squamous Cell - pathology; Case-Control Studies; DNA-directed RNA polymerase; Dysbacteriosis; Dysbiosis - complications; Esophageal cancer; esophageal lavage; Esophageal Neoplasms - microbiology; esophageal SCC; Esophageal Squamous Cell Carcinoma; Esophagus; Head and Neck Neoplasms; Humans; Lipoic acid; Malignancy; Medical research; Microbiota; Microbiota - genetics; Microenvironments; Mouth Neoplasms - microbiology; Nucleotide excision repair; Oral cancer; Oral carcinoma; Oral cavity; oral cavity SCC; oral rinse; Pathogenesis; Pyruvic acid; Risk factors; RNA polymerase; RNA, Ribosomal, 16S - genetics; rRNA 16S; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment; upper aerodigestive microbiota
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.34460

The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case‐control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3‐V4 amplicon sequencing. Compared with their respective non‐SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC‐associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host‐microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies. What's new? Esophageal squamous cell carcinoma and oral cavity squamous cell carcinoma have common risk factors and share oncogenic molecular processes. In this prospective case‐control study, the upper aerodigestive microbiota in patients with esophageal and oral cavity squamous cell carcinoma showed a convergent dysbiosis, pointing to further commonalities between the two cancer types. The shared enriched bacterial genera, which included Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus, may play important roles in the pathogenesis of the two upper aerodigestive malignancies and could potentially serve as biomarkers for cancer screening and patien