Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Although the oral cavity is an easily accessible area for visual examination, the OSCC is more often detected at an advanced stage. The global prevalence of OSCC is around 6%, with increasing trends posing a significant health problem due to the increase in morbidity and mortality. The oral cavity microbiome has been the target of numerous studies, with findings highlighting the significant role of dysbiosis in developing OSCC. Dysbiosis can significantly increase pathobionts (bacteria, viruses, fungi, and parasites) that trigger inflammation through their virulence and pathogenicity factors. In contrast, chronic bacterial inflammation contributes to the development of OSCC. Pathobionts also have other effects, such as the impact on the immune system, which can alter immune responses and contribute to a pro-inflammatory environment. Poor oral hygiene and carbohydrate-rich foods can also increase the risk of developing oral cancer. The risk factors and mechanisms of OSCC development are not yet fully understood and remain a frequent research topic. For this reason, this narrative review concentrates on the issue of dysbiosis as the potential cause of OSCC, as well as the underlying mechanisms involved.

Aggregatibacter actinomycetemcomitans (A. actinomycetecomitans) is a Gram-negative bacterial species that is an essential component of the oral microbiota. Due to its aggregative properties, it plays a role in the pathogenesis of human diseases. The presence of the surface proteins Fim, Briae, and microvesicles enables the bacterium to adhere to the epithelial surface and the tooth’s surface. The presence of leukotoxin A (LtxA), which plays an important role in the pathogenicity of the bacterium, has been associated with both periodontitis and the etiology of rheumatoid arthritis (RA). A. actinomycetecomitans is also associated with several other systemic diseases and complications, such as endocarditis and different abscesses. In addition to leukotoxin A, A. actinomycetecomitans possesses several different virulence factors, including bacteriocins, chemotaxis inhibitory factors, cytotoxic factors, Fc-binding proteins, immunosuppressive factors, lipopolysaccharide collagenase, fibroblast inhibitory factors, antibiotic resistance determinants, adhesins, invasive factors and factors that inhibit the function of polymorphonuclear leukocytes. The ability of A. actinomycetemcomitans lipopolysaccharide to induce macrophages to secrete the interleukins IL-1, IL-1β, and tumor necrosis factor (TNF) is of considerable importance. The primary etiologic factor in the pathogenesis of periodontal disease is the oral biofilm colonized by anaerobic bacteria. Among these, A. actinomycetemcomitans occupies an important place as a facultative anaerobic bacterium. In addition, A. actinomycetemcomitans possesses many virulence factors that contribute to its potential to cause cancer. This article provides an overview of the virulence factors of A. actinomycetecomitans and its association with various systemic diseases, its oncogenic potential, and the treatment options for infections caused by A. actinomycetecomitans.