Skip to main content

Advertisement

SpringerLink
Log in

Simultaneous occurrence of Epstein-Barr virus (EBV) in periodontal pockets and in oral squamous cell carcinoma: a cross-sectional study

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

This study aimed to investigate the detection of Epstein-Barr virus (EBV) in oral squamous cell carcinoma (OSCC) and to verify the concordance of EBV-DNA frequency in subgingival sites and in the OSCC.

Methods

A cross-sectional study with 30 OSCC patients, aged from 44 to 88 years old, was conducted. Samples were collected in subgingival sites and at the OSCC, then submitted to DNA isolation, qPCR, and genotyping. Descriptive statistic was performed to report the frequency of EBV-DNA in all samples, and McNemar test was applied to verify the concordance among the EBV-DNA frequency in both sites.

Results

The individuals presented 62 years old in average, and the majority were male (66.6%). EBV-DNA was detected in 56.7% OSCC lesions. Among the subgroup of 19 dentate individuals, high concordance (73.7%) in both EBV-DNA detection and the absence in subgingival sites and OSCC was observed, and it was statistically significant (p < 0.05).

Conclusions

We report the notable occurrence of EBV-DNA in OSCC; also, the presence of EBV in periodontal sites may contribute to find it in OSCC, although the possible contribution of EBV in the OSCC remains to be investigated.

Clinical relevance.

The identification of this easily accessible site of EBV latent infection may help to improve the patient’s quality of life by maintenance of oral/periodontal health condition and preventing further possible disorders related to the virus, and also encourages new approaches for investigating EBV, periodontitis, and OSCC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Thomson PJ (2018) Perspectives on oral squamous cell carcinoma prevention- proliferation, position, progression and prediction. J Oral Pathol Med 47:803–807. https://doi.org/10.1111/jop.12733

    Article  PubMed  Google Scholar 

  2. Feller L, Lemmer J (2012) Oral squamous cell carcinoma: epidemiology, clinical presentation and treatment. J Cancer Ther 3:263–268. https://doi.org/10.4236/jct.2012.34037

    Article  Google Scholar 

  3. Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45:309–316. https://doi.org/10.1016/j.oraloncology.2008.06.002

    Article  PubMed  Google Scholar 

  4. INCA- Instituto Nacional de Câncer José Alencar Gomes da Silva– INCA. Estimativa 2018/2019: incidência de câncer no Brasil. Rio de Janeiro: INCA, 2018. http://www1.inca.gov.br/rbc/n_64/v01/pdf/15-resenha-estimativa-2018-incidencia-de-cancer-no-brasil.pdf

  5. Zhong LP, Zhang CP, Ren GX, Guo W, William WN Jr, Hong CS, Sun J, Zhu HG, Tu WY, Li J, Cai YL, Yin QM, Wang LZ, Wang ZH, Hu YJ, Ji T, Yang WJ, Ye WM, Li J, He Y, Wang YA, Xu LQ, Zhuang Z, Lee JJ, Myers JN, Zhang ZY (2015) Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma. Oncotarget 30:18707–18714. https://doi.org/10.18632/oncotarget.4531

    Article  Google Scholar 

  6. Chin D, Boyle GM, Porceddu S, Theile DR, Parsons PG, Coman WB (2006) Head and neck cancer: past, present and future. Expert Rev Anticancer Ther 6:1111–1118. https://doi.org/10.1586/14737140.6.7.1111

    Article  PubMed  Google Scholar 

  7. Gallimidi AB, Fischman S, Revach B, Bulvik R, Maliutina A, Rubinstein AM, 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. https://doi.org/10.18632/oncotarget.4209

    Article  PubMed Central  Google Scholar 

  8. Gupta K, Metgud R (2013) Evidences suggesting involvement of viruses in oral squamous cell carcinoma. Patholog Res Int 2013:642496. https://doi.org/10.1155/2013/642496

    Article  PubMed  PubMed Central  Google Scholar 

  9. Higa M, Kinjo T, Kamiyama K, Chinen K, Iwamasa T, Arasaki A, Sunakawa H (2003) Epstein-Barr virus (EBV)-related oral squamous cell carcinoma in Okinawa, a subtropical island, in southern Japan- simultaneously infected with human papillomavirus (HPV). Oral Oncol 39:405–414. https://doi.org/10.1016/s1368-8375(02)00164-1

    Article  PubMed  Google Scholar 

  10. Sand L, Jalouli J (2014) Viruses and oral cancer. is there a link? Microbes Infect 16:371–378. https://doi.org/10.1016/j.micinf.2014.02.009

    Article  PubMed  Google Scholar 

  11. Prabhu SR, Wilson DF (2016) Evidence of Epstein-Barr virus association with head and neck cancers: a review. J Can Dent Assoc 82:g2

    PubMed  Google Scholar 

  12. Tsao SW, Tsang CM, Lo KW (2017) Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond B Biol Sci 372:20160270. https://doi.org/10.1098/rstb.2016.0270

    Article  PubMed  PubMed Central  Google Scholar 

  13. Takada K (2000) Epstein-Barr virus and gastric carcinoma. Mol Pathol 53:255–256. https://doi.org/10.1136/mp.53.5.255

    Article  PubMed  PubMed Central  Google Scholar 

  14. She Y, Nong X, Zhang M (2017) Wang M (2017) Epstein-Barr virus infection and oral squamous cell carcinoma risk: a meta-analysis. PLoS ONE 12:e0186860. https://doi.org/10.1371/journal.pone.0186860.eCollection

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tsao SW, Tsang CM, Pang PS, Zhang G, Chen H, Lo KW (2012) The biology of EBV infection in human epithelial cells. Semin Cancer Biol 22:137–143. https://doi.org/10.1016/j.semcancer.2012.02.004

    Article  PubMed  Google Scholar 

  16. Hadinoto V, Shapiro M, Sun CC, Thorley-Lawson DA (2009) The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output. PLoS Pathog 5:e1000496. https://doi.org/10.1371/journal.ppat.1000496

    Article  PubMed  PubMed Central  Google Scholar 

  17. Gao Z, Lv J, Wang M (2017) Epstein-Barr virus is associated with periodontal diseases: A meta-analysis based on 21 case-control studies. Medicine (Baltimore) 96:e5980. https://doi.org/10.1097/MD.0000000000005980

    Article  Google Scholar 

  18. Agar N, Patel R (2014) Early detection causes and screening of oral cancer. JSM Dent 2:1039

    Google Scholar 

  19. Tonetti MS, Greenwell H, Kornman KS (2018) Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Clin Periodontol 45:S149–S161

    Article  Google Scholar 

  20. Scheutz F, Matee MI, Andsager L, Holm AM, Moshi J, Kagoma C, Mpemba N (1997) Is there an association between periodontal condition and HIV infection. J Clin Periodontol 24:580–587. https://doi.org/10.1111/j.1600-051x.1997.tb00232.x

    Article  PubMed  Google Scholar 

  21. Howlett SE, Castillo HS, Gioeni LJ, Lora J, Robertson JM, Donfack J (2014) Evaluation of DNAstable™ for DNA storage at ambient temperature. Forensic Sci Int Genet 8:170–178. https://doi.org/10.1016/j.fsigen.2013.09.003

    Article  PubMed  Google Scholar 

  22. Mesri EA, Feitelson MA, Munger K (2014) Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe 15:266–282. https://doi.org/10.1016/j.chom.2014.02.011

    Article  PubMed  PubMed Central  Google Scholar 

  23. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim- Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V (2009) WHO International Agency for Research on Cancer Monograph Working Group. a review of human carcinogens- Part B: biological agents. Lancet Oncol 10:321–322. https://doi.org/10.1016/s1470-2045(09)70096-8

    Article  PubMed  Google Scholar 

  24. Cordero OJ, Varela-Calvino R (2018) Oral hygiene might prevent cancer. Heliyon 4:e00879. https://doi.org/10.1016/j.heliyon.2018.e00879

    Article  PubMed  PubMed Central  Google Scholar 

  25. D’Costa J, Saranath D, Sanghvi V, Mehta AR (1998) Epstein-Barr virus in tobacco-induced oral cancers and oral lesions in patients from India. J Oral Pathol Med 27:78–82. https://doi.org/10.1111/j.1600-0714.1998.tb02098.x

    Article  PubMed  Google Scholar 

  26. Kikuchi K, Noguchi Y, Garcia-Nino de Rivera MW, Hoshino M, Sakashita H, Yamada T, Inoue H, Miyazaki Y, Nozaki T, González-López BS, Ide F, Kusama K (2016) Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity. Tumor Biol 37:3389–3404. https://doi.org/10.1007/s13277-015-4167-7

    Article  Google Scholar 

  27. Kikuchi K, Inoue H, Miyazaki Y, Ide F, Kojima M, Kusama K (2017) Epstein-Barr virus (EBV)-associated epithelial and non-epithelial lesions of the oral cavity. Jpn Dent Sci Rev 53:95–109. https://doi.org/10.1016/j.jdsr.2017.01.002

    Article  PubMed  PubMed Central  Google Scholar 

  28. Srivastava AK, Shukla S, Srivastava P, Dhole TN, Nayak MT, Nayak A, Mathur A (2019) Real time detection and quantification of Epstein Barr virus in different grades of oral gingivitis and periodontitis patients. J Exp Ther Oncol 13:9–14

    PubMed  Google Scholar 

  29. Kiprian D, Czarkowska-Paczek B, Wyczalkowska-Tomasik A, Paczek L (2018) Human cytomegalovirus and Epstein-Barr virus infections increase the risk of death in patients with head and neck cancers receiving radiotherapy or radiochemotherapy. Medicine (Baltimore) 97:e13777. https://doi.org/10.1097/MD.0000000000013777

    Article  Google Scholar 

  30. Van Rensburg EJ, Engelbrecht S, Van HW, Raubenheimer E, Schoub BD (1995) Detection of EBV DNA in oral squamous cell carcinomas in a black African population sample. In Vivo (Athens Greece) 9:199–202

    Google Scholar 

  31. Cruz I, Van den Brule AJ, Steenbergen RD, Snijders PJ, Meijer CJ, Walboomers JM, Snow GB, Van der Waal I (1997) Prevalence of Epstein-Barr virus in oral squamous cell carcinomas, premalignant lesions and normal mucosa — a study using the polymerase chain reaction. Oral Oncol 33:182–188. https://doi.org/10.1016/s0964-1955(96)00054-1

    Article  PubMed  Google Scholar 

  32. Kiryanov SA, Levina TA, Polyakov AP, Rebrikova IV, Murashko DA, Konopleva MV, Semenenko TA, Suslov AP (2019) Detection of Epstein-Barr virus genome in oral cavity squamous cell carcinoma samples of Russian patients. Vopr Virusol 64:112–117. https://doi.org/10.18821/0507-4088-2019-64-3-112-117

    Article  PubMed  Google Scholar 

  33. Sample J, Young L, Martin B, Chatman T, Kieff E, Rickinson A, Kieff E (1990) Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. J Virol 64:4084–4092. https://doi.org/10.1128/JVI.64.9.4084-4092.1990

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zimber U, Adldinger HK, Lenoir GM, Vuillaume M, Knebel-Doeberitz MV, Laux G, Desgranges C, Wittmann P, Freese UK, Schneider U, Bornkamm GW (1986) Geographical prevalence of two types ofEpstein-Barr virus. Virology 154:56–66. https://doi.org/10.1016/0042-6822(86)90429-0

    Article  PubMed  Google Scholar 

  35. Smith NA, Baresel PC, Jackson CL, Ogolla S, Toko EN, Heit S, Piriou E, Sumba OP, Middeldrop JM, Colborn KL, Rochford R (2019) Differences in the Epstein-Barr virus gp350 IgA antibody response are associated with increased risk for coinfection with a second strain of Epstein-Barr Virus. J Infect Dis 219:955–963. https://doi.org/10.1093/infdis/jiy601

    Article  PubMed  Google Scholar 

  36. Lung ML, Li SB, Chang RS (1991) Study of Epstein-Barr virus (EBV) transmission by EBV genotyping. J Infect Dis 164:213–214. https://doi.org/10.1093/infdis/164.1.213

    Article  PubMed  Google Scholar 

  37. Lucchesi W, Brady G, Dittrich-Breiholz O, Kracht M, Russ R, Farrell PJ (2008) Differential gene regulation by Epstein-Barr virus type 1 and type 2 EBNA2. J Virol 82:7456–7466. https://doi.org/10.1128/jvi.00223-08

    Article  PubMed  PubMed Central  Google Scholar 

  38. Rickinson AB, Young LS, Rowe M (1987) Influence of the Epstein-Barr virus nuclear antigen EBNA 2 on the growth phenotype of virus-transformed B cells. J Virol 61:1310–1317. https://doi.org/10.1128/JVI.61.5.1310-1317.1987

    Article  PubMed  PubMed Central  Google Scholar 

  39. IARC (International Agency for Research on Cancer) Working Group on the Evaluation of Carcinogenic Risks to Humans. Epstein–Barr virus. In: a review of human carcinogens. B. Biological agents. IARC monograph on the evaluation of carcinogenic risks to humans 100(B). Lyon, France: IARC; 2012. p. 49–92.

  40. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F et al (2009) A review of human carcinogenesis — part B: biological agents. Lancet Oncol 10:321–322

    Article  Google Scholar 

  41. Griffin BE (2000) Epstein-Barr virus (EBV) and human disease: facts, opinions and problems. Mutat Res 462:395–405

    Article  Google Scholar 

  42. Parkin DM (2011) Cancers attributable to infection in the UK in 2010. Br J Cancer 105(suppl 2):S49-56

    Article  Google Scholar 

  43. IARC (International Agency for Research on Cancer) (1997) Working Group on the Evaluation of Carcinogenic Risks to Humans. Nasopharyngeal carcinoma. In: Epstein-Barr virus and Kaposi’s sarcoma herpes virus/human herpesvirus 8. IARC monograph on the evaluation of carcinogenic risks to humans 70. Lyon, France: IARC; p. 164–94.

Download references

Acknowledgements

H.J.S. is recipient of fellowship. R.A.M. is research fellows of CNPq. We also would like to thank Maria Sueli da Silva Kataoka, João de Jesus Viana Pinheiro, Julio Tanos de Lacerda, Maycon Douglas Oliveira Araújo, and Thais dos Santos Fontes Pereira for the technical contribution.

Funding

This study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Finance Code 001), Brazil. We also received financial support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #305493/2018–3, #435644/2018–1).

Author information

Authors and Affiliations

  1. Laboratory of Pathology and Immunohistochemistry (LAPI), School of Dentistry, Universidade Federal do Pará (UFPA), Belém, PA, Brazil

    Humberto Jácome-Santos, Helder Henrique Costa Pinheiro, Ana Cláudia Braga Amoras-Alves & Sérgio de Melo Alves-Junior

  2. Department of Virology, Laboratory of Epstein-Barr Virus, Instituto Evandro Chagas (IEC), Belém, PA, Brazil

    Naira da Silva e Silva

  3. Department of Stomatology & Oral and Maxillofacial Surgery, Hospital Metropolitano Odilon Behrens (HMOB), Belo Horizonte, MG, Brazil

    Renata Gonçalves Resende

  4. Laboratory of Virology, Universidade Federal do Pará (UFPA), Belém, PA, Brazil

    Luiz Fernando Almeida Machado & Igor Brasil-Costa

  5. Hospital das Clínicas (HC), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil

    Guilherme de Souza Silva

  6. Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil

    Humberto Jácome-Santos, Fernando de Oliveira Costa & Ricardo Alves Mesquita

Authors
  1. Humberto Jácome-Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naira da Silva e Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renata Gonçalves Resende
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helder Henrique Costa Pinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luiz Fernando Almeida Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guilherme de Souza Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fernando de Oliveira Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Igor Brasil-Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ana Cláudia Braga Amoras-Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ricardo Alves Mesquita
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sérgio de Melo Alves-Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Humberto Jácome-Santos.

Ethics declarations

Ethical approval.

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Research Ethics Committee of the Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (application number: 2.421.701).

Informed consent.

An informed consent form was obtained from all the patients.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Ana Cláudia Braga Amoras-Alves, Ricardo Alves Mesquita, and Sérgio de Melo Alves-Junior jointly directed this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jácome-Santos, H., da Silva e Silva, N., Resende, R. et al. Simultaneous occurrence of Epstein-Barr virus (EBV) in periodontal pockets and in oral squamous cell carcinoma: a cross-sectional study. Clin Oral Invest 26, 2807–2815 (2022). https://doi.org/10.1007/s00784-021-04258-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-021-04258-z

Keywords

Search

Navigation