Abstract
Oral squamous cell carcinoma (OSCC) remains a pressing public health challenge, with stagnant survival rates and limited progress in preventive strategies. In addition to classical risk factors such as tobacco and alcohol consumption, recent evidence highlights the role of microbial dysbiosis, particularly the overrepresentation of Fusobacterium nucleatum and Porphyromonas gingivalis, in promoting tumor initiation and progression through inflammation, epithelial transformation, and immune escape. This narrative review aims to summarize and discuss the current evidence linking the oral microbiota to the development of OSCC, with a particular focus on the potential role of probiotics as modulators of microbial balance, inflammation, and epithelial homeostasis. Probiotics have emerged as potential modulators of these carcinogenic processes. Emerging data indicate that specific probiotic strains, including Lactobacillus plantarum, Lactobacillus salivarius, Streptococcus salivarius, and Lactobacillus acidophilus, show antiproliferative and immunomodulatory effects in preclinical models. These include the inhibition of oncogenic bacteria, restoration of microbial equilibrium, downregulation of pro-inflammatory pathways, and enhancement of anti-tumor immunity. Engineered probiotics producing guided antimicrobial peptides (gAMPs), synthetic molecules specifically designed to target tumor-promoting microbes, further exemplify the potential of precision microbial modulation. However, most available evidence derives from experimental or small-scale human studies, with limited data directly addressing oral cancer prevention. Probiotics represent a promising, biologically plausible approach to modulating the oral microenvironment in ways that may reduce carcinogenic risk. While preliminary evidence supports their mechanistic and translational potential, robust clinical trials are needed to validate their safety and efficacy as adjuncts in oral cancer prevention.