Nevertheless, in vitro studies, clinical trials, and mouse models of periodontitis/oncogenic-related carcinogenesis confirm that chronic bacterial infection may potentially promote the development of OSCC through direct interaction of periodontal pathogens with neoplastic and precancerous oral epithelial cells via Toll-like receptors (TLRs) P2 × 7, C5aR, or B7H1 receptors. This evidence concerns the gene C5AR1 and periodontitis.