@Article{or.2026.083280,
AUTHOR = {Bianca Maria Messina, Alessandro Polizzi, Elena Jovanova, Angela Angjelova, Francesco Leonforte, Gaetano Isola},
TITLE = {<i>Porphyromonas gingivalis</i> as a Chronic Modulator of Oncogenic Processes in Oral Cancer: A Systematic Review},
JOURNAL = {Oncology Research},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/or/online/detail/28267},
ISSN = {1555-3906},
ABSTRACT = {<b>Objectives:</b> Oral squamous cell carcinoma (OSCC) remains a major global health burden with substantial morbidity, recurrence, and limited improvement in long-term survival. This systematic review aimed to synthesize mechanistic and translational evidence linking <i>Porphyromonas gingivalis</i> to OSCC development, progression, therapeutic resistance, and clinical relevance. <b>Methods:</b> A scoping review was conducted according to the PRISMA-ScR framework. Searches were performed in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and the reference lists of relevant articles using terms related to OSCC, oral cancer, <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), oncogenic signaling, immune modulation, epithelial–mesenchymal transition, therapy resistance, and tumor progression. Findings were synthesized qualitatively. Results: Fifty-four studies were included. Evidence indicates that chronic <i>P</i>. <i>gingivalis</i> exposure may modulate PI3K/Akt, MAPK, NF-κB, STAT3, NDK–ATP–P2X7, IL-6/EZH2/Snai2, miR-21/PDCD4/AP-1, autophagy, epithelial–mesenchymal transition, oxidative stress, epigenetic remodeling, ferroptosis, and stemness-related pathways. <i>P</i>. <i>gingivalis</i> also appears to reshape the tumor immune microenvironment by promoting macrophage and neutrophil remodeling, regulatory T-cell recruitment, PD-L1/checkpoint pathway activation, impaired cytotoxic responses, and resistance to cell death. Clinical and translational data suggest associations with aggressive phenotypes, unfavorable immune landscapes, poorer prognosis, and reduced therapeutic responsiveness, although evidence remains heterogeneous and not uniformly directional. <b>Conclusions:</b> Current evidence supports a model in which <i>P</i>. <i>gingivalis</i> acts as a chronic modulator of OSCC biology rather than a passive bystander. Microbial assessment may inform future risk stratification and microbiome-informed preventive or therapeutic strategies, pending standardized detection methods and prospective clinical validation.},
DOI = {10.32604/or.2026.083280}
}