OBJECTIVES: Oral dysbiosis can accelerate the progression of head and neck squamous cell carcinoma (HNSCC) by fostering a pro-inflammatory, immunosuppressive, and metabolically altered environment. This narrative review examines the relationships between periodontitis-associated bacteria and HNSCC, focusing on their impact on oncogenic pathways, immune modulation, and epigenetic alterations. MATERIALS AND METHODS: A comprehensive search of PubMed and Google Scholar was conducted up to January 28, 2026, without time limitations, using all relevant keywords related to HNSCC, head and neck cancers, periodontitis, and the oral microbiome. RESULTS: Key periodontitis-associated bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, Capnocytophaga gingivalis, and Prevotella intermedia, may play a vital role in HNSCC. These bacteria stimulate several oncogenic pathways, including Wnt/β-catenin, NF-κB, and PI3K/Akt, enabling HNSCC to evade immune responses, trigger epithelial-to-mesenchymal transition and angiogenesis, and encourage cell proliferation and stemness. Furthermore, microbial interactions within the tumor microenvironment significantly impact treatment resistance, particularly in the context of immune checkpoint inhibitor therapy. CONCLUSIONS: Incorporating periodontal screening, microbiome profiling, and bacterial-targeted therapies into oncology could enhance treatment outcomes for HNSCC. Future research should investigate CRISPR-based microbial interventions, targeted epigenetic therapies, and microbiome-driven precision oncology strategies.
Afshar et al. (Mon,) studied this question.