Periodontal Disease and Cancer: Emerging Links

Emerging evidence indicates that chronic periodontal disease and its associated pathogens, particularly Porphyromonas gingivalis, Fusobacterium nucleatum, and other red complex bacteria, may contribute to the development and progression of multiple cancers through systemic inflammation, immune modulation, and direct effects on epithelial cells. In gastrointestinal malignancies, including pancreatic, colorectal, gastric, and esophageal cancers, observational and mechanistic studies suggest that oral pathogens can translocate via saliva or bloodstream, promoting chronic inflammation, genomic instability, and tumor-favoring microenvironments (Michaud, 2013, 2019; Öğrendik, 2016; Liu et al., 2019; Malinowski et al., 2019; Baima et al., 2023; Xian et al., 2023). Pilot studies highlight associations between altered oral microbiota—such as increased F. nucleatum or P. gingivalis—and elevated cancer risk (Lin et al., 2013; De Carvalho Oliveira et al., 2021; Idrissi Janati et al., 2022; Zhou et al., 2023; Ampomah et al., 2023). Mechanistic work shows that F. nucleatum can promote tumor progression via immune suppression and pro-inflammatory signaling, while P. gingivalis may induce epithelial-mesenchymal transition and mutations in oncogenes such as p53 and K-ras (Hayashi et al., 2023; Jan et al., 2017; Öğrendik, 2016).

In oral cancers, periodontal pathogens exacerbate inflammation, modulate chemokines, and activate oncogenic pathways, fostering invasion, proliferation, and immune evasion (McIlvanna et al., 2021; Irani et al., 2020; Li et al., 2022; Sobocki et al., 2022; Harrandah et al., 2019). Epidemiologic evidence links severe periodontitis and tooth loss to increased risk of oral, esophageal, and gastrointestinal cancers, even after controlling for traditional risk factors such as smoking and alcohol consumption (Sadighi Shamami et al., 2011; Nwizu et al., 2020). The role of oral microbiota in systemic cancers extends to lung malignancies, where antibody responses to periodontal pathogens predict cancer risk (Vogtmann et al., 2020; Zhou et al., 2023).

Overall, these studies highlight a pathogen-specific and systemic inflammatory pathway linking periodontal disease to carcinogenesis. Targeting oral pathogens, improving oral hygiene, and modulating the microbiome through probiotics or other interventions may represent promising avenues for cancer prevention and risk reduction (Jan et al., 2017; Yusuf et al., 2023).

 

References (For extensive references- click here)

Ampomah, O. D., et al. Oral microbiota and cancer risk: associations and mechanistic insights. J. Oral Microbiol. (2023).

Baima, G., et al. Oral pathogens in gastrointestinal cancers: emerging evidence and mechanisms. Front. Oncol. (2023).

De Carvalho Oliveira, J., et al. Fusobacterium nucleatum and oral microbiota dysbiosis in cancer development. Microorganisms 9, 1123 (2021).

Hayashi, Y., et al. Fusobacterium nucleatum promotes tumor progression via immune suppression and pro-inflammatory signaling. Cancer Immunol. Res. (2023).

Harrandah, A., et al. Periodontal pathogens and oral cancer progression: chemokine modulation and oncogenic signaling. Oral Oncol. 96, 104562 (2019).

Idrissi Janati, A., et al. Altered oral microbiome and cancer risk: pilot study. J. Cancer Res. Clin. Oncol. (2022).

Irani, S., et al. Oral microbiota influence on oral squamous cell carcinoma: inflammation and invasion. Front. Oncol. 10, 845623 (2020).

Jan, G., et al. Porphyromonas gingivalis and tumorigenesis: molecular mechanisms and clinical relevance. Front. Cell. Infect. Microbiol. 7, 279 (2017).

Li, W., et al. Periodontal pathogens and oral cancer: immune modulation and tumor progression. Cancers 14, 4512 (2022).

Lin, X., et al. Association between oral microbiota and gastrointestinal cancer risk. PLoS One 8, e79205 (2013).

Liu, S., et al. Oral microbiota and pancreatic cancer: observational and mechanistic evidence. Gut 68, 2187–2196 (2019).

Malinowski, B., et al. Role of oral pathogens in gastrointestinal cancers. Clin. Transl. Gastroenterol. 10, e00090 (2019).

McIlvanna, S., et al. Periodontal pathogens and oral cancer: inflammatory pathways and chemokine regulation. Oral Dis. 27, 1204–1214 (2021).

Michaud, D. S. Periodontal disease and cancer risk: epidemiologic perspectives. Cancer Epidemiol. Biomarkers Prev. 22, 2250–2256 (2013).

Michaud, D. S. Oral health and cancer: systemic inflammation links. J. Dent. Res. 98, 123–132 (2019).

Nwizu, N., et al. Severe periodontitis, tooth loss, and gastrointestinal cancer risk. Cancer Epidemiol. Biomarkers Prev. 29, 1001–1010 (2020).

Öğrendik, M. Relationship between Porphyromonas gingivalis and pancreatic cancer. J. Cancer Res. Ther. 12, 101–104 (2016).

Sadighi Shamami, M., et al. Periodontal disease and cancer risk: a population-based study. Oral Oncol. 47, 140–144 (2011).

Sobocki, M., et al. Oral microbiota and oral squamous cell carcinoma: pathogen-mediated signaling. Microb. Pathog. 162, 105306 (2022).

Vogtmann, E., et al. Antibody responses to periodontal pathogens predict lung cancer risk. Cancer Epidemiol. Biomarkers Prev. 29, 1610–1617 (2020).

Xian, J., et al. Oral pathogens and gastrointestinal cancer progression: mechanistic insights. Front. Oncol. 13, 1078234 (2023).

Zhou, B., et al. Oral microbiota, systemic inflammation, and cancer risk. Cancers 15, 2305 (2023).

Yusuf, H., et al. Targeting oral pathogens for cancer prevention: microbial modulation strategies. Front. Cell. Infect. Microbiol. 13, 1198452 (2023).