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Current Oral Health Reports

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Open Access 01-06-2019 | Oral Cancer | Microbiology (C Genco, Section Editor)

The Microbiome of Oral Squamous Cell Carcinomas: a Functional Perspective

Authors: Nezar N. Al-Hebshi, Wenche S. Borgnakke, Newell W. Johnson

Published in: Current Oral Health Reports | Issue 2/2019

Abstract

Purpose of Review

This decade has witnessed increasing interest in the potential role of the oral microbiome in head and neck cancers, particularly oral squamous cell carcinoma (OSCC). Most studies have focused on the bacterial component of the microbiome (bacteriome), but the fungal component (mycobiome) is also receiving attention. In this review, we provide an overview of mechanisms by which the microbiome can contribute to oral carcinogenesis, and summarize results from clinical studies, especially focusing on those reporting functional microbiome analysis. Synthesizing and illustrating the evidence, we also suggest a new “passenger-turning-driver” functional model for the role of the microbiome in oral cancer.

Recent Findings

In vitro studies provide convincing evidence for the carcinogenicity of the periodontal bacteria Fusobacterium nucleatum and Porphyromonas gingivalis. However, results from clinical studies are inconsistent, with significant variations in composition of the microbiome associated with oral cancer. Methodological differences may partially explain the differing conclusion. However, variations observed may also reflect functional redundancy: the phenomenon that different species may be enriched in different samples, but still serve the same functions. Indeed, functional analyses of the bacteriome associated with oral cancer have revealed more consistent results, namely enrichment of a virulent, inflammatory bacteriome in the tumors.

Summary

Apart from oncoviruses associated with a special entity of oral cancer, no consistent evidence implicates specific microbial species in OSCC etiology. Instead, the disturbed function of an initially “passenger” microbiome within the tumor microenvironment likely contributes to tumor progression by sustaining chronic inflammation.

Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on. Cancer. 2018; https://gco.iarc.fr/today. Accessed 19 February, 2019.

Gupta B, Johnson NW, Kumar N. Global epidemiology of head and neck cancers: a continuing challenge. Oncol. 2016;91(1):13–23. https://doi.org/10.1159/000446117.CrossRef

American Cancer Society. Cancer facts & figures 2017. Atlanta: American Cancer Society; 2017.

Petersen PE. Oral cancer prevention and control—the approach of the World Health Organization. Oral Oncol. 2009;45(4–5):454–60. https://doi.org/10.1016/j.oraloncology.2008.05.023.CrossRefPubMed

Gupta B, Johnson NW. Systematic review and meta-analysis of association of smokeless tobacco and of betel quid without tobacco with incidence of oral cancer in South Asia and the Pacific. PLoS One. 2014;9(11):e113385. https://doi.org/10.1371/journal.pone.0113385.CrossRefPubMedPubMedCentral

Emmett S, Jenkins G, Boros S, et al. Low prevalence of human papillomavirus in oral cavity squamous cell carcinoma in Queensland, Australia. ANZ J Surg. 2017;87(9):714–9. https://doi.org/10.1111/ans.13607.CrossRefPubMed

Lingen MW, Xiao W, Schmitt A, et al. Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol. 2013;49(1):1–8. https://doi.org/10.1016/j.oraloncology.2012.07.002.CrossRefPubMed

Shaikh MH, Khan AI, Sadat A, et al. Prevalence and types of high-risk human papillomaviruses in head and neck cancers from Bangladesh. BMC Cancer. 2017;17(1):792. https://doi.org/10.1186/s12885-017-3789-0.CrossRefPubMedPubMedCentral

Sklenicka S, Gardiner S, Dierks EJ, et al. Survival analysis and risk factors for recurrence in oral squamous cell carcinoma: does surgical salvage affect outcome? J Oral Maxillofac Surg. 2010;68(6):1270–5. https://doi.org/10.1016/j.joms.2009.11.016.CrossRefPubMed

10.

Wang B, Zhang S, Yue K, et al. The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases. Chin J Cancer. 2013;32(11):614–8. https://doi.org/10.5732/cjc.012.10219.CrossRefPubMedPubMedCentral

11.

Perera M, Al-Hebshi NN, Speicher DJ, et al. Emerging role of bacteria in oral carcinogenesis: a review with special reference to perio-pathogenic bacteria. J Oral Microbiol. 2016;8(n/a):32762. https://doi.org/10.3402/jom.v8.32762.CrossRefPubMed

12.

Prescott SL. History of medicine: origin of the term microbiome and why it matters. Human Microbiomed J. 2017;4(n/a):24–5. https://doi.org/10.1016/j.humic.2017.05.004.CrossRef

13.

Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature. 2007;449(7164):804–10. https://doi.org/10.1038/nature06244.CrossRefPubMedPubMedCentral

14.

Belizario JE, Napolitano M. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front Microbiol. 2015;6(n/a):1050. https://doi.org/10.3389/fmicb.2015.01050.CrossRefPubMedPubMedCentral

15.

Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14. https://doi.org/10.1038/nature11234.CrossRef

16.

Hooks KB, O’Malley MA. Dysbiosis and its discontents. MBio. 2017;8(5):e01492–17. https://doi.org/10.1128/mBio.01492-17.CrossRefPubMedPubMedCentral

17.

Dupuy AK, David MS, Li L, et al. Redefining the human oral mycobiome with improved practices in amplicon-based taxonomy: discovery of Malassezia as a prominent commensal. PLoS One. 2014;9(3):e90899. https://doi.org/10.1371/journal.pone.0090899.CrossRefPubMedPubMedCentral

18.

Ghannoum MA, Jurevic RJ, Mukherjee PK, et al. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog. 2010;6(1):e1000713. https://doi.org/10.1371/journal.ppat.1000713.CrossRefPubMedPubMedCentral

19.

Perez-Brocal V, Moya A. The analysis of the oral DNA virome reveals which viruses are widespread and rare among healthy young adults in Valencia (Spain). PLoS One. 2018;13(2):e0191867. https://doi.org/10.1371/journal.pone.0191867.CrossRefPubMedPubMedCentral

20.

Van Dyne EA, Henley SJ, Saraiya M, et al. Trends in human papillomavirus-associated cancers—United States, 1999–2015. MMWR Morb Mortal Wkly Rep. 2018;67(33):918–24. https://doi.org/10.15585/mmwr.mm6733a2.CrossRefPubMedPubMedCentral

21.

Johnson NW, Gupta B, Speicher DJ, et al. Chapter 2. Etiology and risk factors. In: Shah JP, Johnson NW, editors. Oral and oropharyngeal cancer. 2nd ed. Boca Raton: CRC Press, Taylor & Francis Group; 2018. p. 19–94.

22.

Shaikh MH, Idris A, Johnson NW, et al. Aurora kinases are a novel therapeutic target for HPV-positive head and neck cancers. Oral Oncol. 2018;86(n/a):105–12. https://doi.org/10.1016/j.oraloncology.2018.09.006.CrossRefPubMed

23.

Tsao SW, Tsang CM, Lo KW. Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond Ser B Biol Sci. 2017;372(1732). https://doi.org/10.1098/rstb.2016.0270.CrossRef

24.

Al-Hebshi NN, Nasher AT, Speicher DJ, et al. Possible interaction between tobacco use and EBV in oral squamous cell carcinoma. Oral Oncol. 2016;59(n/a):e4–5. https://doi.org/10.1016/j.oraloncology.2016.06.005.CrossRefPubMed

25.

He M, Cheng F, da Silva SR, et al. Molecular biology of KSHV in relation to HIV/AIDS-associated oncogenesis. Cancer Treat Res. 2019;177(n/a):23–62. https://doi.org/10.1007/978-3-030-03502-0_2.CrossRefPubMed

26.

Speicher DJ, Wanzala P, D’Lima M, et al. Detecting DNA viruses in oral fluids: evaluation of collection and storage methods. Diagn Microbiol Infect Dis. 2015;82(2):120–7. https://doi.org/10.1016/j.diagmicrobio.2015.02.013.CrossRefPubMed

27.

Edlund A, Santiago-Rodriguez TM, Boehm TK, et al. Bacteriophage and their potential roles in the human oral cavity. J Oral Microbiol. 2015;7(n/a):27423. https://doi.org/10.3402/jom.v7.27423.CrossRefPubMed

28.

Kim SS, Ruiz VE, Carroll JD, et al. Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma. Cancer Lett. 2011;305(2):228–38. https://doi.org/10.1016/j.canlet.2010.07.014.CrossRefPubMed

29.

Markowska J, Fischer N, Markowski M, et al. The role of Chlamydia trachomatis infection in the development of cervical neoplasia and carcinoma. Med Wieku Rozwoj. 2005;9(1):83–6.PubMed

30.

Nagaraja V, Eslick GD. Systematic review with meta-analysis: the relationship between chronic Salmonella typhi carrier status and gall-bladder cancer. Aliment Pharmacol Ther. 2014;39(8):745–50. https://doi.org/10.1111/apt.12655.CrossRefPubMed

31.

Toprak NU, Yagci A, Gulluoglu BM, et al. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006;12(8):782–6. https://doi.org/10.1111/j.1469-0691.2006.01494.x.CrossRefPubMed

32.

Ahn J, Segers S, Hayes RB. Periodontal disease, Porphyromonas gingivalis serum antibody levels and orodigestive cancer mortality. Carcinogenesis. 2012;33(5):1055–8. https://doi.org/10.1093/carcin/bgs112.CrossRefPubMedPubMedCentral

33.

Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22(2):299–306. https://doi.org/10.1101/gr.126516.111.CrossRefPubMedPubMedCentral

34.

Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22(2):292–8. https://doi.org/10.1101/gr.126573.111.CrossRefPubMedPubMedCentral

35.

Michaud DS, Izard J. Microbiota, oral microbiome, and pancreatic cancer. Cancer J. 2014;20(3):203–6. https://doi.org/10.1097/PPO.0000000000000046.CrossRefPubMedPubMedCentral

36.

Yilmaz Ö, Jungas T, Verbeke P, et al. Activation of the phosphatidylinositol 3-kinase/Akt pathway contributes to survival of primary epithelial cells infected with the periodontal pathogen Porphyromonas gingivalis. Infect Immun. 2004;72(7):3743–51. https://doi.org/10.1128/IAI.72.7.3743-3751.2004.CrossRefPubMedPubMedCentral

37.

Mao S, Park Y, Hasegawa Y, et al. Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis. Cell Microbiol. 2007;9(8):1997–2007. https://doi.org/10.1111/j.1462-5822.2007.00931.x.CrossRefPubMedPubMedCentral

38.

Yao L, Jermanus C, Barbetta B, et al. Porphyromonas gingivalis infection sequesters pro-apoptotic Bad through Akt in primary gingival epithelial cells. Mol Oral Microbiol. 2010;25(2):89–101. https://doi.org/10.1111/j.2041-1014.2010.00569.x.CrossRefPubMedPubMedCentral

39.

Moffatt CE, Lamont RJ. Porphyromonas gingivalis induction of microRNA-203 expression controls suppressor of cytokine signaling 3 in gingival epithelial cells. Infect Immun. 2011;79(7):2632–7. https://doi.org/10.1128/IAI.00082-11.CrossRefPubMedPubMedCentral

40.

Yilmaz Ö, Yao L, Maeda K, et al. ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis. Cell Microbiol. 2008;10(4):863–75. https://doi.org/10.1111/j.1462-5822.2007.01089.x.CrossRefPubMed

41.

Kuboniwa M, Hasegawa Y, Mao S, et al. P. gingivalis accelerates gingival epithelial cell progression through the cell cycle. Microbes Infect. 2008;10(2):122–8. https://doi.org/10.1016/j.micinf.2007.10.011.CrossRefPubMed

42.

Pan C, Xu X, Tan L, et al. The effects of Porphyromonas gingivalis on the cell cycle progression of human gingival epithelial cells. Oral Dis. 2014;20(1):100–8. https://doi.org/10.1111/odi.12081.CrossRefPubMed

43.

Uitto VJ, Baillie D, Wu Q, et al. Fusobacterium nucleatum increases collagenase 3 production and migration of epithelial cells. Infect Immun. 2005;73(2):1171–9. https://doi.org/10.1128/IAI.73.2.1171-1179.2005.CrossRefPubMedPubMedCentral

44.

Zhou Y, Sztukowska M, Wang Q, et al. Noncanonical activation of beta-catenin by Porphyromonas gingivalis. Infect Immun. 2015;83(8):3195–203. https://doi.org/10.1128/IAI.00302-15.CrossRefPubMedPubMedCentral

45.

Rubinstein MR, Wang X, Liu W, et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013;14(2):195–206. https://doi.org/10.1016/j.chom.2013.07.012.CrossRefPubMedPubMedCentral

46.

Inaba H, Sugita H, Kuboniwa M, et al. Porphyromonas gingivalis promotes invasion of oral squamous cell carcinoma through induction of proMMP9 and its activation. Cell Microbiol. 2014;16(1):131–45. https://doi.org/10.1111/cmi.12211.CrossRefPubMed

47.

Inaba H, Amano A, Lamont RJ, et al. Involvement of protease-activated receptor 4 in over-expression of matrix metalloproteinase 9 induced by Porphyromonas gingivalis. Med Microbiol Immunol. 2015;204(5):605–12. https://doi.org/10.1007/s00430-015-0389-y.CrossRefPubMed

48.

Ha NH, Woo BH, Kim d J, et al. Prolonged and repetitive exposure to Porphyromonas gingivalis increases aggressiveness of oral cancer cells by promoting acquisition of cancer stem cell properties. Tumour Biol. 2015;36(12):9947–60. https://doi.org/10.1007/s13277-015-3764-9.CrossRefPubMed

49.

Andrian E, Grenier D, Rouabhia M. In vitro models of tissue penetration and destruction by Porphyromonas gingivalis. Infect Immun. 2004;72(8):4689–98. https://doi.org/10.1128/IAI.72.8.4689-4698.2004.CrossRefPubMedPubMedCentral

50.

Groeger S, Domann E, Gonzales JR, et al. B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by Porphyromonas gingivalis. Immunobiology. 2011;216(12):1302–10. https://doi.org/10.1016/j.imbio.2011.05.005.CrossRefPubMed

51.

Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14(2):207–15. https://doi.org/10.1016/j.chom.2013.07.007.CrossRefPubMedPubMedCentral

52.

McCoy AN, Araujo-Perez F, Azcarate-Peril A, et al. Fusobacterium is associated with colorectal adenomas. PLoS ONE. 2013;8(1):e53653. https://doi.org/10.1371/journal.pone.0053653.CrossRefPubMedPubMedCentral

53.

Kurkivuori J, Salaspuro V, Kaihovaara P, et al. Acetaldehyde production from ethanol by oral streptococci. Oral Oncol. 2007;43(2):181–6. https://doi.org/10.1016/j.oraloncology.2006.02.005.CrossRefPubMed

54.

Muto M, Hitomi Y, Ohtsu A, et al. Acetaldehyde production by non-pathogenic Neisseria in human oral microflora: implications for carcinogenesis in upper aerodigestive tract. Int J Cancer. 2000;88(3):342–50. https://doi.org/10.1002/1097-0215(20001101)88:3<342::AID-IJC4>3.0.CO;2-I.CrossRefPubMed

55.

Gainza-Cirauqui ML, Nieminen MT, Novak Frazer L, et al. Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders. J Oral Pathol Med. 2013;42(3):243–9. https://doi.org/10.1111/j.1600-0714.2012.01203.x.CrossRefPubMed

56.

Nieminen MT, Uittamo J, Salaspuro M, et al. Acetaldehyde production from ethanol and glucose by non-Candida albicans yeasts in vitro. Oral Oncol. 2009;45(12):e245–8. https://doi.org/10.1016/j.oraloncology.2009.08.002.CrossRefPubMed

57.

• Nagy KN, Sonkodi I, Szoke I, et al. The microflora associated with human oral carcinomas. Oral Oncol. 1998;34(4):304–8. https://doi.org/10.1016/S1368-8375(98)80012-2 Based on the available culturing techniques, this study was the first to identify compositional differences in the microbial community colonizing the surface of OSCC vs adjacent clinically healthy tissue. CrossRefPubMed

58.

Tateda M, Shiga K, Saijo S, et al. Streptococcus anginosus in head and neck squamous cell carcinoma: implication in carcinogenesis. Int J Mol Med. 2000;6(6):699–703. https://doi.org/10.3892/ijmm.6.6.699.CrossRefPubMed

59.

Morita E, Narikiyo M, Yano A, et al. Different frequencies of Streptococcus anginosus infection in oral cancer and esophageal cancer. Cancer Sci. 2003;94(6):492–6. https://doi.org/10.1111/j.1349-7006.2003.tb01471.x.CrossRefPubMed

60.

Mager DL, Haffajee AD, Devlin PM, et al. The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J Transl Med. 2005;3:27. https://doi.org/10.1186/1479-5876-3-27.CrossRefPubMedPubMedCentral

61.

Sasaki M, Yamaura C, Ohara-Nemoto Y, et al. Streptococcus anginosus infection in oral cancer and its infection route. Oral Dis. 2005;11(3):151–6. https://doi.org/10.1111/j.1601-0825.2005.01051.x.CrossRefPubMed

62.

• Hooper SJ, Crean SJ, Lewis MA, et al. Viable bacteria present within oral squamous cell carcinoma tissue. J Clin Microbiol. 2006;44(5):1719–25. https://doi.org/10.1128/JCM.44.5.1719-1725.2006 This study demonstrated for the first time the presence of a viable microbial community within the tissue of OSCC. CrossRefPubMedPubMedCentral

63.

Hooper SJ, Crean SJ, Fardy MJ, et al. A molecular analysis of the bacteria present within oral squamous cell carcinoma. J Med Microbiol. 2007;56(Pt 12):1651–9. https://doi.org/10.1099/jmm.0.46918-0.CrossRefPubMed

64.

Katz J, Onate MD, Pauley KM, et al. Presence of Porphyromonas gingivalis in gingival squamous cell carcinoma. Int J Oral Sci. 2011;3(4):209–15. https://doi.org/10.4248/IJOS11075.CrossRefPubMedPubMedCentral

65.

Pushalkar S, Mane SP, Ji X, et al. Microbial diversity in saliva of oral squamous cell carcinoma. FEMS Immunol Med Microbiol. 2011;61(3):269–77. https://doi.org/10.1111/j.1574-695X.2010.00773.x.CrossRefPubMedPubMedCentral

66.

Pushalkar S, Ji X, Li Y, et al. Comparison of oral microbiota in tumor and non-tumor tissues of patients with oral squamous cell carcinoma. BMC Microbiol. 2012;12(n/a):144. https://doi.org/10.1186/1471-2180-12-144.CrossRefPubMedPubMedCentral

67.

Schmidt BL, Kuczynski J, Bhattacharya A, et al. Changes in abundance of oral microbiota associated with oral cancer. PLoS One. 2014;9(6):e98741. https://doi.org/10.1371/journal.pone.0098741.CrossRefPubMedPubMedCentral

68.

Al-Hebshi NN, Nasher AT, Idris AM, et al. Robust species taxonomy assignment algorithm for 16S rRNA NGS reads: application to oral carcinoma samples. J Oral Microbiol. 2015;7(n/a):28934. https://doi.org/10.3402/jom.v7.28934.CrossRefPubMed

69.

Guerrero-Preston R, Godoy-Vitorino F, Jedlicka A, et al. 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment. Oncotarget. 2016;7(32):51320–34. https://doi.org/10.18632/oncotarget.9710.CrossRefPubMedPubMedCentral

70.

Hu X, Zhang Q, Hua H, et al. Changes in the salivary microbiota of oral leukoplakia and oral cancer. Oral Oncol. 2016;56(n/a):e6–8. https://doi.org/10.1016/j.oraloncology.2016.03.007.CrossRefPubMed

71.

• Al-Hebshi NN, Nasher AT, Maryoud MY, et al. Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma. Sci Rep. 2017;7(1):1834. https://doi.org/10.1038/s41598-017-02079-3 This is the first attempt to perform functional analysis of the microbiome associated with OSCC and to describe it as being inflammatory. CrossRefPubMedPubMedCentral

72.

Amer A, Galvin S, Healy CM, et al. The microbiome of potentially malignant oral leukoplakia exhibits enrichment for Fusobacterium, Leptotrichia, Campylobacter, and Rothia species. Front Microbiol. 2017;8(2391):2391. https://doi.org/10.3389/fmicb.2017.02391.CrossRefPubMedPubMedCentral

73.

Börnigen D, Ren B, Pickard R, et al. Alterations in oral bacterial communities are associated with risk factors for oral and oropharyngeal cancer. Sci Rep. 2017;7(1):17686. https://doi.org/10.1038/s41598-017-17795-z.CrossRefPubMedPubMedCentral

74.

Guerrero-Preston R, White JR, Godoy-Vitorino F, et al. High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation. Oncotarget. 2017;8(67):110931–48. https://doi.org/10.18632/oncotarget.20677.CrossRefPubMedPubMedCentral

75.

Lee WH, Chen HM, Yang SF, et al. Bacterial alterations in salivary microbiota and their association in oral cancer. Sci Rep. 2017;7(1):16540. https://doi.org/10.1038/s41598-017-16418-x.CrossRefPubMedPubMedCentral

76.

Mukherjee PK, Wang H, Retuerto M, et al. Bacteriome and mycobiome associations in oral tongue cancer. Oncotarget. 2017;8(57):97273–89. https://doi.org/10.18632/oncotarget.21921.CrossRefPubMedPubMedCentral

77.

Shin JM, Luo T, Kamarajan P, et al. Microbial communities associated with primary and metastatic head and neck squamous cell carcinoma—a high Fusobacterial and low Streptococcal signature. Sci Rep. 2017;7(1):9934. https://doi.org/10.1038/s41598-017-09786-x.CrossRefPubMedPubMedCentral

78.

Wang H, Funchain P, Bebek G, et al. Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas. Genome Med. 2017;9(1):14. https://doi.org/10.1186/s13073-017-0405-5.CrossRefPubMedPubMedCentral

79.

Zhao H, Chu M, Huang Z, et al. Variations in oral microbiota associated with oral cancer. Sci Rep. 2017;7(1):11773. https://doi.org/10.1038/s41598-017-11779-9.CrossRefPubMedPubMedCentral

80.

• Hayes RB, Ahn J, Fan X, et al. Association of oral microbiome with risk for incident head and neck squamous cell cancer. JAMA Oncol. 2018;4(3):358–65. https://doi.org/10.1001/jamaoncol.2017.4777 This longitudinal study assessed whether baseline oral microbiome signature can influence the risk of developing OSCC. CrossRefPubMedPubMedCentral

81.

Lim Y, Fukuma N, Totsika M, et al. The performance of an oral microbiome biomarker panel in predicting oral cavity and oropharyngeal cancers. Front Cell Infect Microbiol. 2018;8(n/a):267. https://doi.org/10.3389/fcimb.2018.00267.CrossRefPubMedPubMedCentral

82.

Perera M, Al-Hebshi NN, Perera I, et al. inflammatory bacteriome and oral squamous cell carcinoma. J Dent Res. 2018;97(6):725–32. https://doi.org/10.1177/0022034518767118.CrossRefPubMed

83.

• Yang CY, Yeh YM, Yu HY, et al. Oral microbiota community dynamics associated with oral squamous cell carcinoma staging. Front Microbiol. 2018;9(862):862. https://doi.org/10.3389/fmicb.2018.00862 This study showed the relative abundance of a number of bacterial species to significantly correlate with staging of OSCC.CrossRefPubMedPubMedCentral

84.

Yang SF, Huang HD, Fan WL, et al. Compositional and functional variations of oral microbiota associated with the mutational changes in oral cancer. Oral Oncol. 2018;77:1–8. https://doi.org/10.1016/j.oraloncology.2017.12.005. CrossRefPubMed

85.

•• Yost S, Stashenko P, Choi Y, et al. Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses. Int J Oral Sci. 2018;10(4):32. https://doi.org/10.1038/s41368-018-0037-7 This is the only study so far that used metatranscriptome sequencing to assess the function/gene expression of the microbiome associated with OSCC. Transcripts of virulence factors and pro-inflammatory features were found to be enriched in the tumor samples. CrossRefPubMedPubMedCentral

86.

American Joint Committee on Cancer. AJCC cancer staging manual. 7th Ed. 2010. https://cancerstaging.org/references-tools/deskreferences/Documents/AJCC%207th%20Ed%20Cancer%20Staging%20Manual.pdf. Accessed 19 Feb, 2019.

87.

•• Tian L, Wu A-K, Friedman J, et al. Deciphering functional redundancy in the human microbiome. bioRxiv. 2017;(n/a):176313. https://doi.org/10.1101/176313 This is a key article that provides insight and mathematical modeling of the concept of functional redundancy. It highlights the importance of a function-based approach to studying the human-associated microbiomes and not relying on only microbial profiles based on their abundance.

88.

Krogh P, Hald B, Holmstrup P. Possible mycological etiology of oral mucosal cancer: catalytic potential of infecting Candida albicans and other yeasts in production of N-nitrosobenzylmethylamine. Carcinogenesis. 1987;8(10):1543–8. https://doi.org/10.1093/carcin/8.10.1543.CrossRefPubMed

89.

Rindum JL, Stenderup A, Holmstrup P. Identification of Candida albicans types related to healthy and pathological oral mucosa. J Oral Pathol Med. 1994;23(9):406–12. https://doi.org/10.1111/j.1600-0714.1994.tb00086.x.CrossRefPubMed

90.

Barrett AW, Kingsmill VJ, Speight PM. The frequency of fungal infection in biopsies of oral mucosal lesions. Oral Dis. 1998;4(1):26–31. https://doi.org/10.1111/j.1601-0825.1998.tb00251.x.CrossRefPubMed

91.

McCullough M, Jaber M, Barrett AW, et al. Oral yeast carriage correlates with presence of oral epithelial dysplasia. Oral Oncol. 2002;38(4):391–3. https://doi.org/10.1016/S1368-8375(01)00079-3.CrossRefPubMed

92.

Spolidorio LC, Martins VR, Nogueira RD, et al. The frequency of Candida sp. in biopsies of oral mucosal lesions. [Portugese]. Pesqui Odontol Bras. 2003;17(1):89–93. https://doi.org/10.1590/S1517-74912003000100017.CrossRefPubMed

93.

Hebbar PB, Pai A, Sujatha D. Mycological and histological associations of Candida in oral mucosal lesions. J Oral Sci. 2013;55(2):157–60. https://doi.org/10.2334/josnusd.55.157.CrossRefPubMed

94.

Berkovits C, Toth A, Szenzenstein J, et al. Analysis of oral yeast microflora in patients with oral squamous cell carcinoma. Springerplus. 2016;5(1):1257. https://doi.org/10.1186/s40064-016-2926-6.CrossRefPubMedPubMedCentral

95.

• Perera M, Al-Hebshi NN, Perera I, et al. A dysbiotic mycobiome dominated by Candida albicans is identified within oral squamous-cell carcinomas. J Oral Microbiol. 2017;9(1):1385369. https://doi.org/10.1080/20002297.2017.1385369 This study characterized the mycobiome present within OSCC tissues at the species-level using 16S rRNA sequencing.CrossRefPubMedPubMedCentral

96.

Perera I, Ekanayake L. Prevalence of oral impacts in a Sinhala-speaking older population in urban Sri Lanka. Community Dent Health. 2003;20(4):236–40.PubMed

97.

Tjalsma H, Boleij A, Marchesi JR, et al. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10(8):575–82. https://doi.org/10.1038/nrmicro2819.CrossRefPubMed

98.

Bartold PM, Van Dyke TE. Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts. Periodontol. 2013;62(1):203–17. https://doi.org/10.1111/j.1600-0757.2012.00450.x.CrossRef

99.

Bartold PM, Van Dyke TE. An appraisal of the role of specific bacteria in the initial pathogenesis of periodontitis. J Clin Periodontol. In press. https://doi.org/10.1111/jcpe.13046.CrossRefPubMed

Title: The Microbiome of Oral Squamous Cell Carcinomas: a Functional Perspective
Authors: Nezar N. Al-Hebshi
Wenche S. Borgnakke
Newell W. Johnson
Publication date: 01-06-2019
Publisher: Springer International Publishing
Keywords: Oral Cancer
Streptococci
Oral Cavity Carcinoma
Published in: Current Oral Health Reports / Issue 2/2019
Electronic ISSN: 2196-3002
DOI: https://doi.org/10.1007/s40496-019-0215-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The Microbiome of Oral Squamous Cell Carcinomas: a Functional Perspective

Abstract

Purpose of Review

Recent Findings

Summary

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

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