Skip to main content
Log in

The Oral Microbiome in the Development of Oral Cancer

  • REVIEWS
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract—Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms that regulate metabolism, immune function, and health. There are three types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokines, including interleukins, interferons, and tumor necrosis factor. Second, bacteria can interact directly with host cells by secreting toxins or by binding to membrane receptors. Finally, the production of metabolites by bacteria may also contribute to carcinogenesis. The importance of the bacteria level and composition in the transition of oral precancerous lesions to cancer has been demonstrated. The relationships of changes in microbiome composition with smoking, inflammation in healthy individuals, as well as with the development of oral cancer in patients, have been studied.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.

Similar content being viewed by others

REFERENCES

  1. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. 2022. Cancer statistics, 2022. CA: Cancer J. Clin. 72, 7‒33.

    PubMed  Google Scholar 

  2. 2022. Sostoyanie onkologicheskoi pomoshchi naseleniyu Rossii v 2021 godu. (The State of Cancer Care for the Russian Population in 2021). Kaprin A.D., Starinsky V.V., Shakhzadova A.O., Eds. Moscow: Herzen Moscow Research Institute of Oncology—Branch of the National Medical Research Center of Radiology of the Health Ministry of Russia.

  3. Cullin N., Azevedo Antunes C., Straussman R., Stein-Thoeringer C.K., Elinav E. 2021. Microbiome and cancer. Cancer Cell. 39, 1317‒1341.

    Article  CAS  PubMed  Google Scholar 

  4. Yangyanqiu W., Shuwen H. 2022. Bacterial DNA involvement in carcinogenesis. Front. Cell Infect. Micro-biol. 12, 996778.

    Article  Google Scholar 

  5. Nokhandani N., Poursheikhani A., Alhosseini M.N., Davoodi H. 2021. Bacteria in carcinogenesis and cancer prevention: A review study. Int. J. Cancer Manage. 14. https://doi.org/10.5812/ijcm.107956

  6. Whisner C.M., Athena Aktipis C. 2019. The role of the microbiome in cancer initiation and progression: How microbes and cancer cells utilize excess energy and promote one another’s growth. Curr. Nutr. Rep. 8, 42‒51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gaines S., Williamson A.J., Hyman N., Kandel J. 2018. How the microbiome is shaping our understanding of cancer biology and its treatment. Semin. Colon Rectal Surg. 29, 12‒16.

    Article  Google Scholar 

  8. Chang A.H., Parsonnet J. 2010. Role of bacteria in oncogenesis. Clin. Microbiol. Rev. 23, 837‒857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Contreras A.V., Cocom-Chan B., Hernandez-Mon-tes G., Portillo-Bobadilla T., Resendis-Antonio O. 2016. Host-microbiome interaction and cancer: Potential application in precision medicine. Front. Physiol. 7, 606.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Liu J., Zhang Y. 2022. Intratumor microbiome in cancer progression: Current developments, challenges and future trends. Biomark. Res. 10, 37.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Han Y.W., Shi W., Huang G.T., Kinder Haake S., Park N.H., Kuramitsu H., Genco R.J. 2000. Interactions between periodontal bacteria and human oral epithelial cells: Fusobacterium nucleatum adheres to and invades epithelial cells. Infect. Immun. 68, 3140‒3146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Han Y.W., Redline R.W., Li M., Yin L., Hill G.B., McCormick T.S. 2004. Fusobacterium nucleatum induces premature and term stillbirths in pregnant mice: Implication of oral bacteria in preterm birth. Infect. Immun. 72, 2272‒2279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang S., Li C., Liu J., Geng F., Shi X., Li Q., Lu Z., Pan Y. 2020. Fusobacterium nucleatum promotes epithelial-mesenchymal transiton through regulation of the lncRNA mir4435-2hg/mir-296-5p/Akt2/Snai1 signaling pathway. FEBS J. 287, 4032‒4047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Guo P., Tian Z., Kong X., Yang L., Shan X., Dong B., Ding X., Jing X., Jiang C., Jiang N. 2020. FadA promotes DNA damage and progression of Fusobacterium nucleatum-induced colorectal cancer through up-regulation of Chk2. J. Exp. Clin. Cancer Res. 39, 1‒13.

    Article  Google Scholar 

  15. Rubinstein M.R., Wang X., Liu W., Hao Y., Cai G., Han Y.W. 2013. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe. 14, 195‒206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Odenbreit S., Püls J., Sedlmaier B., Gerland E., Fischer W., Haas R. 2000. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science. 287, 1497‒1500.

    Article  CAS  PubMed  Google Scholar 

  17. Murata-Kamiya N., Kurashima Y., Teishikata Y., Yamahashi Y., Saito Y., Higashi H., Aburatani H., Akiyama T., Peek R., Azuma T. 2007. Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 26, 4617‒4626.

    Article  CAS  PubMed  Google Scholar 

  18. Parida S., Wu S., Siddharth S., Wang G., Muniraj N., Nagalingam A., Hum C., Mistriotis P., Hao H., Tal-bot C.C., Jr., Konstantopoulos K., Gabrielson K.L., Sears C.L., Sharma D. 2021. A procarcinogenic colon microbe promotes breast tumorigenesis and metastatic progression and concomitantly activates Notch and β-catenin axes. Cancer Discovery 11, 1138‒1157.

    Article  CAS  PubMed  Google Scholar 

  19. Cheng W.T., Kantilal H.K., Davamani F. 2020. The mechanism of Bacteroides fragilis toxin contributes to colon cancer formation. Malays. J. Med. Sci. 27, 9.

    PubMed  PubMed Central  Google Scholar 

  20. Wu S., Morin P.J., Maouyo D., Sears C.L. 2003. Bacteroides fragilis enterotoxin induces c-myc expression and cellular proliferation. Gastroenterology. 124, 392‒400.

    Article  CAS  PubMed  Google Scholar 

  21. Lu R., Bosland M., Xia Y., Zhang Y.-G., Kato I., Sun J. 2017. Presence of Salmonella avra in colorectal tumor and its precursor lesions in mouse intestine and human specimens. Oncotarget. 8, 55104.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wu S., Ye Z., Liu X., Zhao Y., Xia Y., Steiner A., Petrof E.O., Claud E.C., Sun J. 2010. Salmonella typhimurium infection increases p53 acetylation in intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 298, G784‒G794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wynendaele E., Verbeke F., D’Hondt M., Hendrix A., Van De Wiele C., Burvenich C., Peremans K., De Wever O., Bracke M., De Spiegeleer B. 2015. Crosstalk between the microbiome and cancer cells by quorum sensing peptides. Peptides. 64, 40‒48.

    Article  CAS  PubMed  Google Scholar 

  24. De Spiegeleer B., Verbeke F., D’Hondt M., Hendrix A., Van De Wiele C., Burvenich C., Peremans K., De Wever O., Bracke M., Wynendaele E. 2015. The quorum sensing peptides PhrG, CSP and EDF promote angiogenesis and invasion of breast cancer cells in vitro. PLoS One. 10, e0119471.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Rossi T., Vergara D., Fanini F., Maffia M., Bravaccini S., Pirini F. 2020. Microbiota-derived metabolites in tumor progression and metastasis. Int. J. Mol. Sci. 21, 5786.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kadosh E., Snir-Alkalay I., Venkatachalam A., May S., Lasry A., Elyada E., Zinger A., Shaham M., Vaalani G., Mernberger M. 2020. The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic. Nature. 586, 133‒138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cañas M.-A., Giménez R., Fábrega M.-J., Toloza L., Baldomà L., Badia J. 2016. Outer membrane vesicles from the probiotic Escherichia coli nissle 1917 and the commensal ECOR12 enter intestinal epithelial cells via clathrin-dependent endocytosis and elicit differential effects on DNA damage. PLoS One. 11, e0160374.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Chmiela M., Walczak N., Rudnicka K. 2018. Helicobacter pylori outer membrane vesicles involvement in the infection development and Helicobacter pylori-related diseases. J. Biomed. Sci. 25, 1‒11.

    Article  Google Scholar 

  29. Zakharzhevskaya N.B., Tsvetkov V.B., Vanyushkina A.A., Varizhuk A.M., Rakitina D.V., Podgorsky V.V., Vishnyakov I.E., Kharlampieva D.D., Manuvera V.A., Lisitsyn F.V. 2017. Interaction of Bacteroides fragilis toxin with outer membrane vesicles reveals new mechanism of its secretion and delivery. Front. Cell. Infect. Microbiol. 7, 2.

    PubMed  PubMed Central  Google Scholar 

  30. Imai S., Ooki T., Murata-Kamiya N., Komura D., Tahmina K., Wu W., Takahashi-Kanemitsu A., Knight C.T., Kunita A., Suzuki N., Del Valle A.A., Tsuboi M., Hata M., Hayakawa Y., Ohnishi N., Ueda K., Fukayama M., Ushiku T., Ishikawa S., Hatakeyama M. 2021. Helicobacter pylori CagA elicits BRCAness to induce genome instability that may underlie bacterial gastric carcinogenesis. Cell Host Microbe. 29, 941‒958.e910.

    Article  CAS  PubMed  Google Scholar 

  31. Pleguezuelos-Manzano C., Puschhof J., Rosendahl Huber A., van Hoeck A., Wood H.M., Nomburg J., Gurjao C., Manders F., Dalmasso G., Stege P.B., Paganelli F.L., Geurts M.H., Beumer J., Mizutani T., Miao Y., van der Linden R., van der Elst S., Garcia K.C., Top J., Willems R.J.L., Giannakis M., Bonnet R., Quirke P., Meyerson M., Cuppen E., van Boxtel R., Clevers H. 2020. Mutational signature in colorectal cancer caused by genotoxic pks + E. coli. Nature. 580, 269‒273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Arthur J.C., Gharaibeh R.Z., Mühlbauer M., Perez-Chanona E., Uronis J.M., McCafferty J., Fodor A.A., Jobin C. 2014. Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer. Nat. Commun. 5, 4724.

    Article  CAS  PubMed  Google Scholar 

  33. Kipanyula M.J., Seke Etet P.F., Vecchio L., Farahna M., Nukenine E.N., Nwabo Kamdje A.H. 2013. Signaling pathways bridging microbial-triggered inflammation and cancer. Cell. Signal. 25, 403‒416.

    Article  CAS  PubMed  Google Scholar 

  34. Riley D.R., Sieber K.B., Robinson K.M., White J.R., Ganesan A., Nourbakhsh S., Dunning Hotopp J.C. 2013. Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples. PLoS Comput. Biol. 9, e1003107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ansari I., Raddatz G., Gutekunst J., Ridnik M., Cohen D., Abu-Remaileh M., Tuganbaev T., Shapiro H., Pikarsky E., Elinav E., Lyko F., Bergman Y. 2020. The microbiota programs DNA methylation to control intestinal homeostasis and inflammation. Nat. Microbiol. 5, 610‒619.

    Article  CAS  PubMed  Google Scholar 

  36. Yang Y., Weng W., Peng J., Hong L., Yang L., Toiyama Y., Gao R., Liu M., Yin M., Pan C., Li H., Guo B., Zhu Q., Wei Q., Moyer M.P., Wang P., Cai S., Goel A., Qin H., Ma Y. 2017. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating Toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21. Gastroenterology. 152, 851‒866.e824.

    Article  CAS  PubMed  Google Scholar 

  37. Fulbright L.E., Ellermann M., Arthur J.C. 2017. The microbiome and the hallmarks of cancer. PLoS Pathog. 13, e1006480.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bhatt A.P., Redinbo M.R., Bultman S.J. 2017. The role of the microbiome in cancer development and therapy. CA—Cancer J. Clin. 67, 326‒344.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hsiao Y.-C., Liu C.-W., Yang Y., Feng J., Zhao H., Lu K. 2023. DNA damage and the gut microbiome: From mechanisms to disease outcomes. DNA. 3, 13‒32.

    Article  Google Scholar 

  40. Nejman D., Livyatan I., Fuks G., Gavert N., Zwang Y., Geller L.T., Rotter-Maskowitz A., Weiser R., Mallel G., Gigi E., Meltser A., Douglas G.M., Kamer I., Gopalakrishnan V., Dadosh T., Levin-Zaidman S., Avnet S., Atlan T., Cooper Z.A., Arora R., Cogdill A.P., Khan M.A.W., Ologun G., Bussi Y., Weinberger A., Lotan-Pompan M., Golani O., Perry G., Rokah M., Bahar-Shany K., Rozeman E.A., Blank C.U., Ronai A., Shaoul R., Amit A., Dorfman T., Kremer R., Cohen Z.R., Harnof S., Siegal T., Yehuda-Shnaidman E., Gal-Yam E.N., Shapira H., Baldini N., Langille M.G.I., Ben-Nun A., Kaufman B., Nissan A., Golan T., Dadiani M., Levanon K., Bar J., Yust-Katz S., Barshack I., Peeper D.S., Raz D.J., Segal E., Wargo J.A., Sandbank J., Shental N., Straussman R. 2020. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science. 368, 973‒980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Jin C., Lagoudas G.K., Zhao C., Bullman S., Bhutkar A., Hu B., Ameh S., Sandel D., Liang X.S., Mazzilli S., Whary M.T., Meyerson M., Germain R., Blainey P.C., Fox J.G., Jacks T. 2019. Commensal microbiota promote lung cancer development via γδT cells. Cell. 176, 998‒1013.e1016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Forbes N.S. 2010. Engineering the perfect (bacterial) cancer therapy. Nat. Rev. Cancer. 10, 785‒794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Baik S.C., Youn H.S., Chung M.H., Lee W.K., Cho M.J., Ko G.H., Park C.K., Kasai H., Rhee K.H. 1996. Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa. Cancer Res. 56, 1279‒1282.

    CAS  PubMed  Google Scholar 

  44. Bagheri N., Salimzadeh L., Shirzad H. 2018. The role of T helper 1-cell response in Helicobacter pylori-infection. Microb. Pathog. 123, 1‒8.

    Article  CAS  PubMed  Google Scholar 

  45. Engevik M.A., Danhof H.A., Ruan W., Engevik A.C., Chang-Graham A.L., Engevik K.A., Shi Z., Zhao Y., Brand C.K., Krystofiak E.S., Venable S., Liu X., Hirschi K.D., Hyser J.M., Spinler J.K., Britton R.A., Versalovic J. 2021. Fusobacterium nucleatum secretes outer membrane vesicles and promotes intestinal inflammation. mBio. 12 (2), e02706‒20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Parhi L., Alon-Maimon T., Sol A., Nejman D., Shhadeh A., Fainsod-Levi T., Yajuk O., Isaacson B., Abed J., Maalouf N., Nissan A., Sandbank J., Yehuda-Shnaidman E., Ponath F., Vogel J., Mandelboim O., Granot Z., Straussman R., Bachrach G. 2020. Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression. Nat. Commun. 11, 3259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Abreu M.T., Peek R.M., Jr. 2014. Gastrointestinal malignancy and the microbiome. Gastroenterology. 146, 1534‒1546.e1533.

  48. Pushalkar S., Hundeyin M., Daley D., Zambirinis C.P., Kurz E., Mishra A., Mohan N., Aykut B., Usyk M., Torres L.E., Werba G., Zhang K., Guo Y., Li Q., Akkad N., Lall S., Wadowski B., Gutierrez J., Kochen Rossi J.A., Herzog J.W., Diskin B., Torres-Hernandez A., Leinwand J., Wang W., Taunk P.S., Savadkar S., Janal M., Saxena A., Li X., Cohen D., Sartor R.B., Saxena D., Miller G. 2018. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discovery. 8, 403‒416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kostic A.D., Chun E., Robertson L., Glickman J.N., Gallini C.A., Michaud M., Clancy T.E., Chung D.C., Lochhead P., Hold G.L., El-Omar E.M., Brenner D., Fuchs C.S., Meyerson M., Garrett W.S. 2013. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 14, 207‒215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Campbell C., McKenney P.T., Konstantinovsky D., Isaeva O.I., Schizas M., Verter J., Mai C., Jin W.B., Guo C.J., Violante S., Ramos R.J., Cross J.R., Kadaveru K., Hambor J., Rudensky A.Y. 2020. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature. 581, 475‒479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Roberti M.P., Yonekura S., Duong C.P.M., Picard M., Ferrere G., Tidjani Alou M., Rauber C., Iebba V., Lehmann C.H.K., Amon L., Dudziak D., Derosa L., Routy B., Flament C., Richard C., Daillère R., Fluckiger A., Van Seuningen I., Chamaillard M., Vincent A., Kourula S., Opolon P., Ly P., Pizzato E., Becharef S., Paillet J., Klein C., Marliot F., Pietrantonio F., Benoist S., Scoazec J.-Y., Dartigues P., Hollebecque A., Malka D., Pagès F., Galon J., Gomperts Boneca I., Lepage P., Ryffel B., Raoult D., Eggermont A., Vanden Berghe T., Ghiringhelli F., Vandenabeele P., Kroemer G., Zitvogel L. 2020. Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. Nat. Med. 26, 919‒931.

    Article  CAS  PubMed  Google Scholar 

  52. Dutzan N., Kajikawa T., Abusleme L., Greenwell-Wild T., Zuazo C.E., Ikeuchi T., Brenchley L., Abe T., Hurabielle C., Martin D., Morell R.J., Freeman A.F., Lazarevic V., Trinchieri G., Diaz P.I., Holland S.M., Belkaid Y., Hajishengallis G., Moutsopoulos N.M. 2018. A dysbiotic microbiome triggers Th17 cells to mediate oral mucosal immunopathology in mice and humans. Sci. Transl. Med. 10 (463), eaat0797.

  53. Pandiyan P., Bhaskaran N., Zou M., Schneider E., Jayaraman S., Huehn J. 2019. Microbiome dependent regulation of Tregs and Th17 cells in mucosa. Front. Immunol. 10, 426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang C., Xu C., Gao L., Li X., Zhao C. 2021. Porphyromonas gingivalis lipopolysaccharide promotes T-hel per17 cell differentiation by upregulating Delta-like ligand 4 expression on CD14+ monocytes. Peer J. 9, e11094.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Marques H.S., de Brito B.B., da Silva F.A.F., Santos M.L.C., de Souza J.C.B., Correia T.M.L., Lopes L.W., Neres N.S.M., Dórea R., Dantas A.C.S., Morbeck L.L.B., Lima I.S., de Almeida A.A., Dias M.R.J., de Melo F.F. 2021. Relationship between Th17 immune response and cancer. W. J. Clin. Oncol. 12, 845‒867.

    Article  Google Scholar 

  56. Guo Z.C., Jumatai S., Jing S.L., Hu L.L., Jia X.Y., Gong Z.C. 2021. 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. Oncol. Lett. 21, 189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gholizadeh P., Eslami H., Kafil H.S. 2017. Carcinogenesis mechanisms of Fusobacterium nucleatum. Biomed. Pharmacother. 89, 918‒925.

    Article  CAS  PubMed  Google Scholar 

  58. Gao Y., Bi D., Xie R., Li M., Guo J., Liu H., Guo X., Fang J., Ding T., Zhu H., Cao Y., Xing M., Zheng J., Xu Q., Xu Q., Wei Q., Qin H. 2021. Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer. Signal. Transduct. Target Ther. 6, 398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gur C., Ibrahim Y., Isaacson B., Yamin R., Abed J., Gamliel M., Enk J., Bar-On Y., Stanietsky-Kaynan N., Coppenhagen-Glazer S., Shussman N., Almogy G., Cuapio A., Hofer E., Mevorach D., Tabib A., Ortenberg R., Markel G., Miklić K., Jonjic S., Brennan C.A., Garrett W.S., Bachrach G., Mandelboim O. 2015. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor tigit protects tumors from immune cell attack. Immunity. 42, 344‒355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gholizadeh P., Eslami H., Yousefi M., Asgharzadeh M., Aghazadeh M., Kafil H.S. 2016. Role of oral microbiome on oral cancers, a review. Biomed. Pharmacother. 84, 552‒558.

    Article  CAS  PubMed  Google Scholar 

  61. Rajagopala S.V., Vashee S., Oldfield L.M., Suzuki Y., Venter J.C., Telenti A., Nelson K.E. 2017. The human microbiome and cancer. Cancer Prev. Res. 10, 226‒234.

    Article  Google Scholar 

  62. Zhao H., Chu M., Huang Z., Yang X., Ran S., Hu B., Zhang C., Liang J. 2017. Variations in oral microbiota associated with oral cancer. Sci. Rep. 7, 11773.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Deo P.N., Deshmukh R. 2019. Oral microbiome: Unveiling the fundamentals. J. Oral. Maxillofac. Pathol. 23, 122‒128.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Kilian M., Chapple I.L., Hannig M., Marsh P.D., Meuric V., Pedersen A.M., Tonetti M.S., Wade W.G., Zaura E. 2016. The oral microbiome—an update for oral healthcare professionals. Br. Dent. J. 221, 657‒666.

    Article  CAS  PubMed  Google Scholar 

  65. Takeshita T., Kageyama S., Furuta M., Tsuboi H., Takeuchi K., Shibata Y., Shimazaki Y., Akifusa S., Ninomiya T., Kiyohara Y., Yamashita Y. 2016. Bacterial diversity in saliva and oral health-related conditions: The Hisayama Study. Sci. Rep. 6, 22164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zaura E., Nicu E.A., Krom B.P., Keijser B.J. 2014. Acquiring and maintaining a normal oral microbiome: Current perspective. Front. Cell. Infect. Microbiol. 4, 85.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Turnbaugh P.J., Ley R.E., Hamady M., Fraser-Liggett C.M., Knight R., Gordon J.I. 2007. The human microbiome project. Nature. 449, 804‒810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Dewhirst F.E., Chen T., Izard J., Paster B.J., Tanner A.C., Yu W.H., Lakshmanan A., Wade W.G. 2010. The human oral microbiome. J. Bacteriol. 192, 5002‒5017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Morrison A.G., Sarkar S., Umar S., Lee S.T.M., Thomas S.M. 2023. The contribution of the human oral microbiome to oral disease: A review. Microorganisms. 11 (2), 318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wu J., Peters B.A., Dominianni C., Zhang Y., Pei Z., Yang L., Ma Y., Purdue M.P., Jacobs E.J., Gapstur S.M., Li H., Alekseyenko A.V., Hayes R.B., Ahn J. 2016. Cigarette smoking and the oral microbiome in a large study of American adults. ISME J. 10, 2435‒2446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Grover N., Sharma J., Sengupta S., Singh S., Singh N., Kaur H. 2016. Long-term effect of tobacco on unstimulated salivary pH. J. Oral Maxillofac. Pathol. 20, 16‒19.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kanwar A., Sah K., Grover N., Chandra S., Singh R.R. 2013. Long-term effect of tobacco on resting whole mouth salivary flow rate and pH: An institutional based comparative study. Eur. J. Gen. Dent. 2, 296‒299.

    Article  Google Scholar 

  73. Kenney E.B., Saxe S.R., Bowles R.D. 1975. The effect of cigarette smoking on anaerobiosis in the oral cavity. J. Periodontol. 46, 82‒85.

    Article  CAS  PubMed  Google Scholar 

  74. Brook I. 2011. The impact of smoking on oral and nasopharyngeal bacterial flora. J. Dent. Res. 90, 704‒710.

    Article  CAS  PubMed  Google Scholar 

  75. Sopori M. 2002. Effects of cigarette smoke on the immune system. Nat. Rev. Immunol. 2, 372‒377.

    Article  CAS  PubMed  Google Scholar 

  76. Pushalkar S., Paul B., Li Q., Yang J., Vasconcelos R., Makwana S., González J.M., Shah S., Xie C., Janal M.N., Queiroz E., Bederoff M., Leinwand J., Solarewicz J., Xu F., Aboseria E., Guo Y., Aguallo D., Gomez C., Kamer A., Shelley D., Aphinyana-phongs Y., Barber C., Gordon T., Corby P., Li X., Saxena D. 2020. Electronic cigarette aerosol modulates the oral microbiome and increases risk of infection. iScience. 23, 100884.

  77. Yang I., Rodriguez J., Young Wright C., Hu Y.J. 2023. Oral microbiome of electronic cigarette users: A cross-sectional exploration. Oral Dis. 29, 1875‒1884.

    Article  PubMed  Google Scholar 

  78. Dal Maso L., Torelli N., Biancotto E., Di Maso M., Gini A., Franchin G., Levi F., La Vecchia C., Serraino D., Polesel J. 2016. Combined effect of tobacco smoking and alcohol drinking in the risk of head and neck cancers: A re-analysis of case-control studies using bi-dimensional spline models. Eur. J. Epidemiol. 31, 385‒393.

    Article  CAS  PubMed  Google Scholar 

  79. Socransky S.S., Haffajee A.D., Cugini M.A., Smith C., Kent R.L., Jr. 1998. Microbial complexes in subgingival plaque. J. Clin. Periodontol. 25, 134‒144.

    Article  CAS  PubMed  Google Scholar 

  80. Hajishengallis G., Liang S., Payne M.A., Hashim A., Jotwani R., Eskan M.A., McIntosh M.L., Alsam A., Kirkwood K.L., Lambris J.D., Darveau R.P., Curtis M.A. 2011. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 10, 497‒506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hajishengallis G., Lamont R.J. 2012. Beyond the red complex and into more complexity: The polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol. Oral Microbiol. 27, 409‒419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Persson G.R. 2005. Immune responses and vaccination against periodontal infections. J. Clin. Periodontol. 32 (Suppl 6), 39‒53.

    Article  CAS  PubMed  Google Scholar 

  83. Meisel P., Holtfreter B., Biffar R., Suemnig W., Kocher T. 2012. Association of periodontitis with the risk of oral leukoplakia. Oral Oncol. 48, 859‒863.

    Article  PubMed  Google Scholar 

  84. Petersen P.E., Bourgeois D., Ogawa H., Estupinan-Day S., Ndiaye C. 2005. The global burden of oral diseases and risks to oral health. Bull. W. Health Organ. 83, 661‒669.

    Google Scholar 

  85. Tezal M., Sullivan M.A., Hyland A., Marshall J.R., Stoler D., Reid M.E., Loree T.R., Rigual N.R., Merzianu M., Hauck L., Lillis C., Wactawski-Wende J., Scannapieco F.A. 2009. Chronic periodontitis and the incidence of head and neck squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 18, 2406‒2412.

    Article  PubMed  Google Scholar 

  86. Chocolatewala N., Chaturvedi P., Desale R. 2010. The role of bacteria in oral cancer. Indian J. Med. Paediatr. Oncol. 31, 126‒131.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Fitzsimonds Z.R., Rodriguez-Hernandez C.J., Bagaitkar J., Lamont R.J. 2020. From beyond the pale to the pale riders: The emerging association of bacteria with oral cancer. J. Dent. Res. 99, 604‒612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Karpiński T.M. 2019. Role of oral microbiota in cancer development. Microorganisms. 7 (1), 20.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Mauceri R., Coppini M., Vacca D., Bertolazzi G., Panzarella V., Di Fede O., Tripodo C., Campisi G. 2022. Salivary microbiota composition in patients with oral squamous cell carcinoma: a systematic review. Cancers (Basel). 14 (21), 5441.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Ohshima J., Wang Q., Fitzsimonds Z.R., Miller D.P., Sztukowska M.N., Jung Y.J., Hayashi M., Whiteley M., Lamont R.J. 2019. Streptococcus gordonii programs epithelial cells to resist ZEB2 induction by Porphyromonas gingivalis. Proc. Natl. Acad. Sci. U. S. A. 116, 8544‒8553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Al-Hebshi N.N., Nasher A.T., Maryoud M.Y., Homeida H.E., Chen T., Idris A.M., Johnson N.W. 2017. Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma. Sci. Rep. 7, 1834.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Hayes R.B., Ahn J., Fan X., Peters B.A., Ma Y., Yang L., Agalliu I., Burk R.D., Ganly I., Purdue M.P., Freedman N.D., Gapstur S.M., Pei Z. 2018. Association of oral microbiome with risk for incident head and neck squamous cell cancer. JAMA Oncol. 4, 358‒365.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Schmidt B.L., Kuczynski J., Bhattacharya A., Huey B., Corby P.M., Queiroz E.L., Nightingale K., Kerr A.R., DeLacure M.D., Veeramachaneni R., Olshen A.B., Albertson D.G. 2014. Changes in abundance of oral microbiota associated with oral cancer. PLoS One. 9, e98741.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Binder Gallimidi A., Fischman S., Revach B., Bulvik R., Maliutina A., Rubinstein A.M., Nussbaum G., Elkin M. 2015. Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Oncotarget. 6, 22613‒22623.

    Article  PubMed  Google Scholar 

  95. Wu J.S., Zheng M., Zhang M., Pang X., Li L., Wang S.S., Yang X., Wu J.B., Tang Y.J., Tang Y.L., L-iang X.H. 2018. Porphyromonas gingivalis promotes 4‑nitroquinoline-1-oxide-induced oral carcinogenesis with an alteration of fatty acid metabolism. Front. Microbiol. 9, 2081.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Shin J.M., Luo T., Kamarajan P., Fenno J.C., Rickard A.H., Kapila Y.L. 2017. Microbial communities associated with primary and metastatic head and neck squamous cell carcinoma—a high Fusobacterial and low Streptococcal signature. Sci. Rep. 7, 9934.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Yang C.Y., Yeh Y.M., Yu H.Y., Chin C.Y., Hsu C.W., Liu H., Huang P.J., Hu S.N., Liao C.T., Chang K.P., Chang Y.L. 2018. Oral microbiota community dynamics associated with oral squamous cell carcinoma staging. Front. Microbiol. 9, 862.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Yang J., He P., Zhou M., Li S., Zhang J., Tao X., Wang A., Wu X. 2022. Variations in oral microbiome and its predictive functions between tumorous and healthy individuals. J. Med. Microbiol. 71 (8). https://doi.org/10.1099/jmm.0.001568

  99. Eun Y.G., Lee J.W., Kim S.W., Hyun D.W., Bae J.W., Lee Y.C. 2021. Oral microbiome associated with lymph node metastasis in oral squamous cell carcinoma. Sci. Rep. 11, 23176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Tota J.E., Anderson W.F., Coffey C., Califano J., Cozen W., Ferris R.L., St John M., Cohen E.E., Chaturvedi A.K. 2017. Rising incidence of oral tongue cancer among white men and women in the United States, 1973‒2012. Oral Oncol. 67, 146‒152.

    Article  PubMed  Google Scholar 

  101. Zhang Z., Feng Q., Li M., Li Z., Xu Q., Pan X., Chen W. 2022. Age-related cancer-associated microbiota potentially promotes oral squamous cell cancer tumorigenesis by distinct mechanisms. Front. Microbiol. 13, 852566.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The work was carried out with the financial support of the Grant of the President of the Russian Federation no. MK-1940.2022.3.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. S. Kolegova.

Ethics declarations

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This work does not contain any studies involving human and animal subjects.

CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

Additional information

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kolegova, E.S., Schegoleva, A.A., Kononova, L.A. et al. The Oral Microbiome in the Development of Oral Cancer. Mol Biol 58, 205–215 (2024). https://doi.org/10.1134/S0026893324020092

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893324020092

Keywords:

Navigation