{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:03:28Z","timestamp":1790701408317,"version":"4.1.0"},"reference-count":72,"publisher":"IMR Press","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Oral squamous cell carcinoma (OSCC) develops within a complex inflammatory microenvironment where chronic mucosal inflammation and microbial dysbiosis may contribute to malignant transformation. Increasing evidence suggests that periodontal pathogens associated with chronic gingival inflammation can influence epithelial signaling, immune responses, and tumor progression. This scoping review aimed to map current molecular, genomic, and immunological evidence linking chronic gingival inflammation and periodontal pathogen\u2013associated dysbiosis to OSCC. Following the Population-Concept-Context (PCC) framework, electronic searches were conducted in PubMed, Scopus, and Web of Science through February 2026. Original studies investigating mechanistic links between periodontal inflammation, microbial dysbiosis, and OSCC in human samples, in vitro models, or animal models were included. Data were extracted on microbial drivers, oncogenic signaling pathways, immune modulation, and genomic or epigenetic alterations. A total of 46 studies were included, suggesting that periodontal pathogens, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, may activate oncogenic signaling pathways such as NF-\u03baB, PI3K\/Akt, Wnt\/\u03b2-catenin, and TGF-\u03b2. Evidence from in vitro, animal, and human studies indicates that these pathways may contribute to epithelial-mesenchymal transition (EMT), tumor invasion, and resistance to apoptosis. Microbial exposure has also been associated with modulation of the tumor immune microenvironment, including macrophage polarization, suppression of cytotoxic T-cell responses, and enhanced immune checkpoint signaling. In addition, genomic and transcriptomic studies have identified dysregulated genes and microRNAs associated with inflammation-driven carcinogenesis. Overall, chronic gingival inflammation and periodontal dysbiosis appear to contribute to OSCC development through interconnected mechanisms involving inflammatory and cytokine signalling, microbe sensing and innate immune activation, immune suppression and tumor immune escape, EMT, invasion and metastatic signaling, and metabolic reprogramming with regulatory networks. However, as current evidence is largely derived from in vitro and animal studies with limited prospective clinical data, well-designed longitudinal human studies are needed to confirm these associations and support biomarkers discovery and novel preventive or therapeutic strategies targeting early oncogenic events in inflamed oral tissues.<\/jats:p>","DOI":"10.31083\/fbl53502","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:21:51Z","timestamp":1790698911000},"source":"Crossref","is-referenced-by-count":0,"title":["From Inflamed Gingiva to Invasive Malignancy: Molecular Crosstalk in Oral Carcinogenesis: A Scoping Review"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1089-2598","authenticated-orcid":true,"given":"Elena","family":"Jovanova","sequence":"first","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3231-0704","authenticated-orcid":true,"given":"Angela","family":"Angjelova","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2607-2734","authenticated-orcid":true,"given":"Roberto","family":"Campagna","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life, San Raffaele Roma University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6717-8899","authenticated-orcid":true,"given":"Alessandro","family":"Polizzi","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"},{"name":"International Research Center on Periodontal and Systemic Health \u201cPerioHealth\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2009-4393","authenticated-orcid":true,"given":"Anand","family":"Marya","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Puthisastra, 12211 Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-6992","authenticated-orcid":true,"given":"Gaetano","family":"Isola","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"},{"name":"International Research Center on Periodontal and Systemic Health \u201cPerioHealth\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Prostakishina EA, Sidenko EA, Kolegova ES, Patysheva MR, Kononova GA, Choinzonov EL. Premalignant lesions of the oral cavity: a narrative review of factors and mechanisms of transformation into cancer. International Journal of Oral and Maxillofacial Surgery. 2025; 54: 479\u2013493.","DOI":"10.1016\/j.ijom.2024.12.006"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Jo\u015bko-Ochojska J, Rygiel K, Postek-Stefa\u0144ska L. Diseases of the oral cavity in light of the newest epigenetic research: Possible implications for stomatology. Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University. 2019; 28: 397\u2013406.","DOI":"10.17219\/acem\/76060"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Li S, Liu X, Zhou Y, Acharya A, Savkovic V, Xu C, et al. Shared genetic and epigenetic mechanisms between chronic periodontitis and oral squamous cell carcinoma. Oral Oncology. 2018; 86: 216\u2013224.","DOI":"10.1016\/j.oraloncology.2018.09.029"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Mishra MK, Gupta S, Shivangi, Sharma M, Sehgal S. The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer. Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2023; 25: 3332\u20133344.","DOI":"10.1007\/s12094-023-03192-8"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Wang S, Nie F, Yin Q, Tian H, Gong P, Ju J, et al. Periodontitis promotes tumor growth and immune evasion via PD-1\/PD-L1. Cancer Immunology, Immunotherapy: CII. 2024; 74: 22.","DOI":"10.1007\/s00262-024-03865-5"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Gabusi A, Gissi DB, Grillini S, Stefanini M, Tarsitano A, Marchetti C, et al. Shared epigenetic alterations between oral cancer and periodontitis: A preliminary study. Oral Diseases. 2023; 29: 2052\u20132060.","DOI":"10.1111\/odi.14251"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Reyes M, Urra H, Pe\u00f1a-Oyarz\u00fan D. Evaluating the link between periodontitis and oral squamous cell carcinoma through Wnt\/\u03b2-catenin pathway: a critical review. Frontiers in Oral Health. 2025; 6: 1575721.","DOI":"10.3389\/froh.2025.1575721"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Shao W, Fujiwara N, Mouri Y, Kisoda S, Yoshida K, Yoshida K, et al. Conversion from epithelial to partial-EMT phenotype by Fusobacterium nucleatum infection promotes invasion of oral cancer cells. 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Cell Adhesion & Migration. 2018; 12: 127\u2013137.","DOI":"10.1080\/19336918.2017.1322253"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Akbari E, Epstein JB, Samim F. Unveiling the Hidden Links: Periodontal Disease, Fusobacterium Nucleatum, and Cancers. Current Oncology Reports. 2024; 26: 1388\u20131397.","DOI":"10.1007\/s11912-024-01591-w"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Imamura Y, Makita Y, Masuno K, Oh H. Inhibitory Mechanism of IL-6 Production by Orento in Oral Squamous Cell Carcinoma Cell Line CAL27 Stimulated by Pathogen-Associated Molecular Patterns from Periodontopathogenic Porphyromonas gingivalis. International Journal of Molecular Sciences. 2022; 24: 697.","DOI":"10.3390\/ijms24010697"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"de Castro LR, de Oliveira LD, Milan TM, Eskenazi APE, Bighetti-Trevisan RL, de Almeida OGG, et al. 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Oral Diseases. 2024; 30: 1873\u20131886.","DOI":"10.1111\/odi.14700"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Qin Y, Li Z, Liu T, Ma J, Liu H, Zhou Y, et al. Prevotella intermedia boosts OSCC progression through ISG15 upregulation: a new target for intervention. Journal of Cancer Research and Clinical Oncology. 2024; 150: 206.","DOI":"10.1007\/s00432-024-05730-5"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Vadovics M, Ho J, Igaz N, Alf\u00f6ldi R, Rakk D, Veres \u00c9, et al. Candida albicans Enhances the Progression of Oral Squamous Cell Carcinoma In Vitro and In Vivo. mbio. 2021; 13: e0314421.","DOI":"10.1128\/mBio.03144-21"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Pigossi SC, Oliveira JA, de Medeiros MC, Soares LFF, D'Silva NJ. Demystifying the link between periodontitis and oral cancer: a systematic review integrating clinical, pre-clinical, and in vitro data. 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International Journal of Nanomedicine. 2025; 20: 6659\u20136674.","DOI":"10.2147\/IJN.S491473"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Zhang Y, Xu L, Naijibai M, Li J, Ling B. Mechanism of Porphyromonas gingivalis Inducing the Formation of a Local Immunosuppressive Microenvironment in Oral Squamous Cell Carcinoma. Journal of Sichuan University (Medical Sciences) = Sichuan Da Xue Xue Bao Yi Xue Ban. 2025; 56: 746\u2013753.  (In Chinese)","DOI":"10.12182\/20250560602"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Yuan Q, Wu H, Tan H, Wang X, Cao Y, Chen G. Oral Microbial Dysbiosis Driven by Periodontitis Facilitates Oral Squamous Cell Carcinoma Progression. Cancers. 2025; 17: 2181.","DOI":"10.3390\/cancers17132181"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Dang J, Bian YQ, Sun JY, Chen F, Dong GY, Liu Q, et al. MicroRNA-137 promoter methylation in oral lichen planus and oral squamous cell carcinoma. Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2013; 42: 315\u2013321.","DOI":"10.1111\/jop.12012"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Liu B, Hu J, Zhao H, Zhao L, Pan S. MicroRNA-155-5p Contributes to 5-Fluorouracil Resistance Through Down-Regulating TP53INP1 in Oral Squamous Cell Carcinoma. Frontiers in Oncology. 2022; 11: 706095.","DOI":"10.3389\/fonc.2021.706095"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"\u0160piljak B, Ozreti\u0107 P, Brailo V, \u0160krinjar I, Lon\u010dar Brzak B, Andabak Rogulj A, et al. Microbial dysbiosis and host-microbe interactions in proliferative verrucous leukoplakia: insights into carcinogenic potential. Archives of Microbiology. 2025; 208: 65.","DOI":"10.1007\/s00203-025-04611-w"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Hu CC, Wang SG, Gao Z, Qing MF, Pan S, Liu YY, et al. Emerging salivary biomarkers for early detection of oral squamous cell carcinoma. World Journal of Clinical Oncology. 2025; 16: 103803.","DOI":"10.5306\/wjco.v16.i4.103803"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Peters MDJ, Marnie C, Tricco AC, Pollock D, Munn Z, Alexander L, et al. Updated methodological guidance for the conduct of scoping reviews. JBI Evidence Synthesis. 2020; 18: 2119\u20132126.","DOI":"10.11124\/JBIES-20-00167"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Chen Q, Pang X, Liu K, Wang H, Qiu T, Luo GF, et al. Porphyromonas gingivalis outer membrane vesicles promote oral tumorigenesis through suppressing innate immune surveillance. Microbiological Research. 2025; 301: 128296.","DOI":"10.1016\/j.micres.2025.128296"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Mu\u00f1oz-Grez CP, Vidal MA, Rojas TB, Ferrada LE, Zu\u00f1iga FA, Vera AA, et al. Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression. International Journal of Oral Science. 2025; 17: 1.","DOI":"10.1038\/s41368-024-00326-8"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Zhou Y, Qin Y, Ma J, Li Z, Heng W, Zhang L, et al. Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment. Experimental Hematology & Oncology. 2024; 13: 33.","DOI":"10.1186\/s40164-024-00500-y"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Zhang S, Li C, Liu J, Geng F, Shi X, Li Q, et al. Fusobacterium nucleatum promotes epithelial-mesenchymal transiton through regulation of the lncRNA MIR4435-2HG\/miR-296-5p\/Akt2\/SNAI1 signaling pathway. The FEBS Journal. 2020; 287: 4032\u20134047.","DOI":"10.1111\/febs.15233"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Lan Z, Zou KL, Cui H, Zhao YY, Yu GT. Porphyromonas gingivalis suppresses oral squamous cell carcinoma progression by inhibiting MUC1 expression and remodeling the tumor microenvironment. Molecular Oncology. 2024; 18: 1174\u20131188.","DOI":"10.1002\/1878-0261.13517"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Sztukowska MN, Ojo A, Ahmed S, Carenbauer AL, Wang Q, Shumway B, et al. Porphyromonas gingivalis initiates a mesenchymal-like transition through ZEB1 in gingival epithelial cells. Cellular Microbiology. 2016; 18: 844\u2013858.","DOI":"10.1111\/cmi.12554"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Seto-Tetsuo F, Katase N, Sasaki Y, Yukitake H, Naito M. Supernatants from DNase-deficient Prevotella intermedia strains enhance oral squamous cell carcinoma cell migration and invasion by activating inflammatory and epithelial-mesenchymal transition pathways. Biochemical and Biophysical Research Communications. 2026; 805: 153304.","DOI":"10.1016\/j.bbrc.2026.153304"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Wei K, Ma Y, Xu J, Hu S, Zheng H, Liu Y, et al. Oral and intratumoral microbiota influence tumor immunity and patient survival. Frontiers in Immunology. 2025; 16: 1572152.","DOI":"10.3389\/fimmu.2025.1572152"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Zhu W, Shen W, Wang J, Xu Y, Zhai R, Zhang J, et al. Capnocytophaga gingivalis is a potential tumor promotor in oral cancer. Oral Diseases. 2024; 30: 353\u2013362.","DOI":"10.1111\/odi.14376"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Peng RT, Sun Y, Zhou XD, Liu SY, Han Q, Cheng L, et al. Treponema denticola Promotes OSCC Development via the TGF-\u03b2 Signaling Pathway. Journal of Dental Research. 2022; 101: 704\u2013713.","DOI":"10.1177\/00220345211067401"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Kashima K, Saito T, Kajikawa H, Kawashima A, Ueyama A, Uzawa N, et al. Impact of oral anaerobic bacteria on the tumor immune microenvironment and prognosis of oral cancer. Journal of Translational Medicine. 2025; 23: 1267.","DOI":"10.1186\/s12967-025-07189-5"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Zhang XY, Li YT, Guo J, Feng Y, Han Q, Zhang SH, et al. Saliva from oral squamous cell carcinoma patients promotes tumor progression via Inflammation, stromal remodeling, and metabolic reprogramming in a mouse model. BMC Oral Health. 2025; 26: 16.","DOI":"10.1186\/s12903-025-07413-0"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Zang X, Li X, Sun R, Zhang X, Li Z, Cheng Z. Intratumoral microbiota drive immune evasion and disease progression in oral squamous cell carcinoma. BDJ Open. 2025; 11: 89.","DOI":"10.1038\/s41405-025-00385-x"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Zhang R, Takigawa H, Maruyama H, Nambu T, Mashimo C, Okinaga T. Fisetin Inhibits Periodontal Pathogen-Induced EMT in Oral Squamous Cell Carcinoma via the Wnt\/\u03b2-Catenin Pathway. Nutrients. 2025; 17: 3522.","DOI":"10.3390\/nu17223522"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Su SC, Chang LC, Huang HD, Peng CY, Chuang CY, Chen YT, et al. Oral microbial dysbiosis and its performance in predicting oral cancer. Carcinogenesis. 2021; 42: 127\u2013135.","DOI":"10.1093\/carcin\/bgaa062"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Sun J, Tang Q, Yu S, Xie M, Zheng W, Chen G, et al. F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production. EBioMedicine. 2023; 88: 104444.","DOI":"10.1016\/j.ebiom.2023.104444"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Inaba H, Sugita H, Kuboniwa M, Iwai S, Hamada M, Noda T, et al. Porphyromonas gingivalis promotes invasion of oral squamous cell carcinoma through induction of proMMP9 and its activation. Cellular Microbiology. 2014; 16: 131\u2013145.","DOI":"10.1111\/cmi.12211"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Ha NH, Woo BH, Kim DJ, Ha ES, Choi JI, Kim SJ, et al. Prolonged and repetitive exposure to Porphyromonas gingivalis increases aggressiveness of oral cancer cells by promoting acquisition of cancer stem cell properties. Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine. 2015; 36: 9947\u20139960.","DOI":"10.1007\/s13277-015-3764-9"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Chen X, Lei H, Cheng Y, Fang S, Sun W, Zhang X, et al. CXCL8, MMP12, and MMP13 are common biomarkers of periodontitis and oral squamous cell carcinoma. Oral Diseases. 2024; 30: 390\u2013407.","DOI":"10.1111\/odi.14419"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Omori Y, Noguchi K, Kitamura M, Makihara Y, Omae T, Hanawa S, et al. Bacterial Lipopolysaccharide Induces PD-L1 Expression and an Invasive Phenotype of Oral Squamous Cell Carcinoma Cells. Cancers. 2024; 16: 343.","DOI":"10.3390\/cancers16020343"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Wen L, Mu W, Lu H, Wang X, Fang J, Jia Y, et al. Porphyromonas gingivalis Promotes Oral Squamous Cell Carcinoma Progression in an Immune Microenvironment. Journal of Dental Research. 2020; 99: 666\u2013675.","DOI":"10.1177\/0022034520909312"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Wei W, Li J, Shen X, Lyu J, Yan C, Tang B, et al. Oral Microbiota from Periodontitis Promote Oral Squamous Cell Carcinoma Development via \u03b3\u03b4 T Cell Activation. MSystems. 2022; 7: e0046922.","DOI":"10.1128\/msystems.00469-22"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Nie F, Zhang J, Tian H, Zhao J, Gong P, Wang H, et al. The role of CXCL2-mediated crosstalk between tumor cells and macrophages in Fusobacterium nucleatum-promoted oral squamous cell carcinoma progression. Cell Death & Disease. 2024; 15: 277.","DOI":"10.1038\/s41419-024-06640-7"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Karri RL, Amrutha R, Shrinivas, Bojji M, Kumar KM, Benarji KA. Analyzing Pooled Microarray Gene Expression Data to Uncover Common Pathways in Periodontitis and Oral Squamous Cell Carcinoma from the Gene Expression Omnibus. Journal of Pharmacy & Bioallied Sciences. 2024; 16: S1515\u2013S1521.","DOI":"10.4103\/jpbs.jpbs_1180_23"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Li M, Li C, Wei W, Chen C, Wang B, Gong Z, et al. Study on the correlation between the expression of Porphyromonas gingivalis, tumor-associated macrophages and the clinical prognosis of oral squamous cell carcinoma. Shanghai Journal of Stomatology = Shanghai Kou Qiang Yi Xue. 2025; 34: 132\u2013138.","DOI":"10.19439\/j.sjos.2025.02.004"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Li Z, Fu R, Wen X, Zhang L. Network analysis reveals miRNA crosstalk between periodontitis and oral squamous cell carcinoma. BMC Oral Health. 2023; 23: 19.","DOI":"10.1186\/s12903-022-02704-2"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Chang C, Wang H, Liu J, Pan C, Zhang D, Li X, et al. Porphyromonas gingivalis Infection Promoted the Proliferation of Oral Squamous Cell Carcinoma Cells through the miR-21\/PDCD4\/AP-1 Negative Signaling Pathway. ACS Infectious Diseases. 2019; 5: 1336\u20131347.","DOI":"10.1021\/acsinfecdis.9b00032"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Mohamadnia A, Bayat M, Norouzi M, Gharayagh Zandi Z, Shirzadian F, Kazempoor Dizaji M, et al. The Role of Oral Microbiota in the Development of Oral Squamous Cell Carcinoma Using MicroRNA and Apoptosis-Related Gene Expression: An Exploratory Study. Asian Pacific Journal of Cancer Prevention: APJCP. 2025; 26: 1225\u20131231.","DOI":"10.31557\/APJCP.2025.26.4.1225"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Khoshbayan A, Narimisa N, Razavi S, Shariati A, Tavakoli-Yaraki M, Darban-Sarokhalil D, et al. The interactions of Fusobacterium nucleatum and Porphyromonas gingivalis with microRNAs: contributions to oral squamous cell carcinoma. Molecular Biology Reports. 2025; 52: 821.","DOI":"10.1007\/s11033-025-10926-0"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Liao X, Si H, Lai Y, Zhang X, Feng Y, Zhou T, et al. Porphyromonas gingivalis-OMVs promote the epithelial-mesenchymal transition of oral squamous cell carcinoma by inhibiting ferroptosis through the NF-\u03baB pathway. Journal of Oral Microbiology. 2025; 17: 2482924.","DOI":"10.1080\/20002297.2025.2482924"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Guo ZC, Jing SL, Jia XY, Elayah SA, Xie LY, Cui H, et al. Porphyromonas gingivalis promotes the progression of oral squamous cell carcinoma by stimulating the release of neutrophil extracellular traps in the tumor immune microenvironment. Inflammation Research. 2024; 73: 693\u2013705.","DOI":"10.1007\/s00011-023-01822-z"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"Inaba H, Amano A, Lamont RJ, Murakami Y. Involvement of protease-activated receptor 4 in over-expression of matrix metalloproteinase 9 induced by Porphyromonas gingivalis. Medical Microbiology and Immunology. 2015; 204: 605\u2013612.","DOI":"10.1007\/s00430-015-0389-y"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"Guo ZC, Jumatai S, Jing SL, Hu LL, Jia XY, Gong ZC. Bioinformatics and immunohistochemistry analyses of expression levels and clinical significance of CXCL2 and TANs in an oral squamous cell carcinoma tumor microenvironment of Prophyromonas gingivalis infection. Oncology Letters. 2021; 21: 189.","DOI":"10.3892\/ol.2021.12450"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Neuzillet C, Marchais M, Vacher S, Hilmi M, Schnitzler A, Meseure D, et al. Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients. Scientific Reports. 2021; 11: 7870.","DOI":"10.1038\/s41598-021-86816-9"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"Baraniya D, Chitrala KN, Al-Hebshi NN. Global transcriptional response of oral squamous cell carcinoma cell lines to health-associated oral bacteria - an in vitro study. Journal of Oral Microbiology. 2022; 14: 2073866.","DOI":"10.1080\/20002297.2022.2073866"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"Tsai MS, Chen YY, Chen WC, Chen MF. Streptococcus mutans promotes tumor progression in oral squamous cell carcinoma. Journal of Cancer. 2022; 13: 3358\u20133367.","DOI":"10.7150\/jca.73310"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"Zhao F, An R, Yu S, Ma Y, Liu W, Sheng C, et al. Fusobacterium nucleatum in cancer: Interactions with microbiota, tumour colonisation and cancer progression. Clinical and Translational Medicine. 2026; 16: e70704.","DOI":"10.1002\/ctm2.70704"},{"key":"ref68","doi-asserted-by":"publisher","unstructured":"Zhou Y, Meyle J, Groeger S. Periodontal pathogens and cancer development. Periodontology 2000. 2024; 96: 112\u2013149.","DOI":"10.1111\/prd.12590"},{"key":"ref69","doi-asserted-by":"publisher","unstructured":"Jiang SS, Chen YX, Fang JY. Fusobacterium nucleatum: ecology, pathogenesis and clinical implications. Nature Reviews. Microbiology. 2026; 24: 197\u2013214.","DOI":"10.1038\/s41579-025-01237-z"},{"key":"ref70","doi-asserted-by":"publisher","unstructured":"Chen S, Xu Y, Zhuo W, Zhang L. The emerging role of lactate in tumor microenvironment and its clinical relevance. Cancer Letters. 2024; 590: 216837.","DOI":"10.1016\/j.canlet.2024.216837"},{"key":"ref71","doi-asserted-by":"publisher","unstructured":"Wang X, He X, Zhong B. Oral microbiota: the overlooked catalyst in cancer initiation and progression. Frontiers in Cell and Developmental Biology. 2025; 12: 1479720.","DOI":"10.3389\/fcell.2024.1479720"},{"key":"ref72","doi-asserted-by":"publisher","unstructured":"Lamont RJ, Hajishengallis G. Polymicrobial synergy and dysbiosis in inflammatory disease. 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