The Role of the Microbiome in Oropharyngeal Squamous Cell Carcinoma: A Systematic Review

Objective: This systematic review aimed to investigate existing evidence regarding the implications of the microbiome in the initiation and progression of oropharyngeal squamous cell carcinoma (OPSCC). Methods: PubMed, Scopus, and Cochrane Library systematic searches were conducted according to the PRISMA statements to identify the relevant studies examining microbiome signatures, underlying molecular mechanisms, and their associations with clinical and oncological outcomes in OPSCC. The bias analysis was conducted with the MINORS. Results: Of the 83 identified papers, 12 met the inclusion criteria (298 OPSCC patients). Spirochaetes and most Bacteroidetes may be predominant in OPSCC versus control specimens, while Proteobacteria may be predominant in control tissues compared to tumor. Leptotrichia, Selenomonas, and Treponema trended to be overrepresented in OPSCC compared to control specimens. Neisseria, Porphyromonas, Rothia, Streptococcus, and Veillonela were predominantly reported in normal compared to OPSCC patient specimens. Microbiome compositional shifts were associated with chemoradiation response, HPV status, and addictions. Methodological heterogeneity was noted in sampling protocols, control selection, and analytical approaches, with limited statistical power due to small cohort sizes. Conclusions: OPSCC demonstrates different microbiome signatures from healthy tissues, influenced by HPV status and addictions. A microbiome shift is plausible from pre- to post-chemoradiotherapy, with the baseline microbiome acting as a predictive response factor; however, the low number of studies and substantial methodological heterogeneity across investigations limit the drawing of valid conclusions. The identification of key species is important in the development of OPSCC for developing personalized medicine considering bacterial mediators in terms of prevention, and targeted therapy using the microbiome-tumor-host interaction pathways.