Abstract
The human oral cavity harbors a diverse and dynamic microbial ecosystem, including bacteriophages (phages), which play a critical role in shaping the microbial community structure. Bacteriophages, viruses that specifically target and infect bacteria, have been increasingly recognized for their potential to influence both microbial balance and disease progression within the oral environment. Recent studies suggest that bacteriophages not only modulate the composition of the oral microbiome but also play an essential role in the pathogenesis and treatment of oral cancer. This review aims to explore the complex crosstalk between bacteriophages and oral health related to oral carcinogenesis, with a particular focus on their emerging roles in oral carcinogenesis and therapeutic interventions. Oral cancer, a major global health concern, is often associated with microbial dysbiosis and chronic inflammation, both of which contribute to tumor progression. Fusobacterium nucleatum, a key bacterial species implicated in oral carcinogenesis, has been shown to promote tumor growth, enhance immune evasion, and exacerbate inflammation within the tumor microenvironment. Bacteriophages offer a promising strategy to selectively target and eliminate such pathogenic bacteria such as Fusobacterium nucleatum, thereby restoring microbial balance and reducing the pro-tumorigenic effects of bacterial infections. Through the disruption of tumor-associated biofilms and modulation of cancer-promoting bacterial populations, phages may help mitigate the inflammatory responses that drive oral cancer progression. Additionally, phage therapy could complement existing treatments by sensitizing cancer cells to chemotherapy and immunotherapy. Beyond their direct antibacterial effects, genetically engineered bacteriophages present novel opportunities for targeted cancer therapy. Advances in synthetic biology have enabled the development of phages capable of delivering therapeutic payloads, such as anti-cancer peptides, cytotoxic agents, and immune modulators. These engineered phages can be designed to selectively target bacterial species that influence tumor progression, offering a highly specific and precision-based approach to oncology. Moreover, phages can serve as vectors for cancer vaccines, facilitating antigen presentation and enhancing immune responses against tumor cells. In addition to therapeutic applications, bacteriophages hold promise in the field of cancer diagnostics. The ability of phages to selectively bind to specific bacterial biomarkers associated with oral cancer could be leveraged for early disease detection and non-invasive screening. Phage-based biosensors, for instance, have shown potential in identifying cancer-associated microbial signatures, paving the way for innovative diagnostic tools that could improve early intervention and patient outcomes. Despite their potential, several challenges must be addressed before phage-based strategies can be fully integrated into clinical practice. Phage resistance, immune system clearance, and regulatory barriers pose significant hurdles to the widespread adoption of phage therapy. Additionally, the complex interactions between bacteriophages, host immunity, and the tumor microenvironment require further investigation to optimize therapeutic efficacy and safety. Advancing research on bacteriophages in the context of oral cancer could revolutionize current treatment paradigms, providing more targeted, efficient, and patient-friendly alternatives to conventional therapies. By harnessing the natural specificity and adaptability of bacteriophages, clinicians and researchers can develop innovative approaches to combat oral cancer, ultimately improving patient care and clinical outcomes.