Sains Malaysiana 48(9)(2019): 1969–1974

http://dx.doi.org/10.17576/jsm-2019-4809-18

The Association between Epstein-Barr virus (EBV) Past Infection with the Risk of Oral Squamous Cell Carcinoma (OSCC)

(Hubung Kait antara Jangkitan Lepas Virus Epstein Barr (EBV) dengan Risiko Karsinoma Sel Skuama Mulut (OSCC))

JESINDA P KERISHNAN¹, MING-KIT MAH¹, NURUL AIN BINTI MOHD FAWZI¹, ANAND RAMANATHAN^2,3, GHEE-SEONG LIM⁴, AZWATEE ABDUL AZIZ⁴, USHARANI BALASINGAM⁵ & YENG CHEN¹*

¹Department of Oral & Craniofacial Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

²Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

³Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

⁴Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

⁵Faculty of Law, University of Malaya, 50603, Kuala Lumpur, Federal Territory, Malaysia

Received: 9 February 2019/Accepted: 11 June 2019

ABSTRACT

The association of Epstein-Barr virus (EBV) with oral cancer has been widely reported in the past. However, previous studies mainly focused on the current infection of EBV without acknowledging the possibility of past infection in patients which may lead to oral cancer development. The present study aims to investigate the correlation between past EBV infections with Oral Squamous Cell Carcinoma (OSCC). Both Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies against EBV were screened to detect the presence of EBV in sera of OSCC patients using Enzyme-Linked Immunosorbent Assay (ELISA). The use of IgM antibody against EBV confirms current infection in patients, whereas IgG antibody would predict past infection throughout patients’ lifetime. Through the present study, we would be able to confirm whether patients with past EBV infection have a significant risk in developing oral cancer. ELISA tests were carried out to detect the presence of EBV IgG and IgM in 206 OSCC and control serum samples. Statistical analysis was performed using SPSS 12.0.1. Our results had shown that 96.6% (n = 199) of OSCC samples and 97.2% (n = 130) control were positive with EBV VCA IgG, however, none of the OSCC and control samples was positive for EBV VCA IgM. The presence of EBV VCA IgG in both OSCC and control suggest that past EBV infection does not play a significant role as a risk indicator for OSCC. Therefore, the association between EBV and OSCC was not well demonstrated in this study.

Keywords: Enzyme-linked immunosorbent assay; Epstein-Barr virus; immunoglobulin G (IgG); immunoglobulin M (IgM); oral squamous cell carcinoma

ABSTRAK

Hubung kait virus Epstein-Barr (EBV) dengan kanser mulut telah banyak dilaporkan sebelum ini. Namun demikian, kajian terdahulu lebih tertumpu kepada jangkitan semasa EBV tanpa mengambil kira kebarangkalian jangkitan masa lalu pada pesakit yang boleh menyebabkan perkembangan kanser mulut. Tujuan kajian ini dijalankan adalah untuk mengkaji korelasi antara jangkitan EBV yang lalu dengan Karsinoma Sel Skuama Mulut (OSCC). Kedua-dua antibodi Imunoglobulin M (IgM) dan Imunoglobulin M (IgG) terhadap EBV telah dikesan menggunakan Asai Imunojerapan Berpaut Enzim (ELISA) untuk mengenal pasti kehadiran EBV dalam sera pesakit OSCC. Antibodi IgM terhadap EBV digunakan untuk mengesahkan jangkitan semasa pada pesakit, manakala antibodi IgG dapat menjangkakan kebarangkalian jangkitan masa lalu sepanjang hayat pesakit. Melalui kajian ini, kami boleh mengesahkan sama ada pesakit yang mengalami jangkitan EBV yang lalu mempunyai tahap risiko tinggi dalam permulaan OSCC. Ujian ELISA dijalankan untuk mengesan kehadiran EBV IgG dan IgM dalam 206 sampel serum OSCC dan kawalan. Analisis statistik dijalankan menggunakan SPSS 12.0.1. Berdasarkan hasil kajian ini, didapati 96.6% (n = 199) sampel OSCC dan 97.2% (n = 130) sampel kawalan, positif dengan EBV VCA IgG. Akan tetapi, tiada sampel OSCC dan kawalan positif terhadap EBV VCA IgM. Kehadiran IgG VCA EBV dalam kedua-dua sampel OSCC dan kawalan mencadangkan bahawa jangkitan EBV yang lalu tidak memainkan peranan penting sebagai penanda risiko terhadap OSCC. Oleh yang demikian, hubung kait antara EBV dan OSCC tidak dapat dibentangkan dengan baik dalam kajian ini.

Kata kunci: Asai imunojerapan berpaut enzim; imunoglobulin G (IgG); imunoglobulin M (IgM); karsinoma sel skuama mulut; virus Epstein-Barr

REFERENCES

Abbott, R.J., Pachnio, A., Pedroza-Pacheco, I., Leese, A.M., Begum, J., Long, H.M., Croom-Carter, D., Stacey, A., Moss, P.A.H. & Hislop, A.D. 2017. Asymptomatic primary infection with Epstein-Barr virus: Observations on young adult cases. Journal of Virology 91(21): e00382-17.

Acharya, S., Ekalaksananan, T., Vatanasapt, P., Loyha, K., Phusingha, P., Promthet, S., Kongyingyoes, B. & Pientong, C. 2015. Association of Epstein-Barr virus infection with oral squamous cell carcinoma in a case - Control study. Journal of Oral Pathology & Medicine 44(4): 252-257.

Arbach, H., Viglasky, V., Lefeu, F., Guinebretiere, J.M., Ramirez, V., Bride, N., Boualaga, N., Bauchet, T., Peyrat, J.P. & Mathieu, M.C. 2006. Epstein-Barr virus (EBV) genome and expression in breast cancer tissue: Effect of EBV infection of breast cancer cells on resistance to paclitaxel (Taxol). Journal of Virology 80(2): 845-853.

Bamoulid, J., Courivaud, C., Coaquette, A., Crépin, T., Carron, C., Gaiffe, E., Roubiou, C., Rebibou, J.M. & Ducloux, D. 2017. Late persistent positive EBV viral load and risk of solid cancer in kidney transplant patients. Transplantation 101(6): 1473-1478.

Cohen, J.I. 2015. Primary immunodeficiencies associated with EBV disease. In Epstein Barr Virus, edited by Münz, C. Volume 1. Springer, Cham. pp. 241-265.

Creager, A.J., Maia, D.M. & Funkhouser, W.K. 1998. Epstein- Barr virus-associated renal smooth muscle neoplasm: Report of a case with review of the literature. Arch. Pathol. Lab. Med. 122(3): 277-281.

Danielsson, K., Nylander, E., Sjöström, M. & Ebrahimi, M. 2018. Epstein-Barr virus is not detected in mucosal lichen planus. Medicina Oral, Patologia Oral y Cirugia Bucal. 23(5): e560-e563.

de Lima, M.A.P., Neto, P.J.N., Lima, L.P.M., Júnior, J.G., Teixeira Junior, A.G., Teodoro, I.P.P., Facundo, H.T., da Silva, C.G.L. & Lima, M.V.A. 2018. Association between Epstein-Barr virus (EBV) and cervical carcinoma: A meta-analysis. Gynecologic Oncology 148(2): 317-328.

de Oliveira, D.E., Müller-Coan, B.G. & Pagano, J.S. 2016. Viral carcinogenesis beyond malignant transformation: EBV in the progression of human cancers. Trends in Microbiology 24(8): 649-664.

Evans, A.S. 2013. Viral Infections of Humans: Epidemiology and Control, edited by Kaslow, R.A., Stanberry, L.R. & LeDuc, J.W. New York: Springer Science & Business Media.

Farrell, P.J. 2019. Epstein-Barr virus and cancer. Annual Review of Pathology: Mechanisms of Disease 14: 29-53.

Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Piñeros, M., Znaor, A., Soerjomataram, I. & Bray, F. 2018. Global cancer observatory: Cancer today. Lyon, France: International Agency for Research on Cancer.

Gupta, K. & Metgud, R. 2013. Evidences suggesting involvement of viruses in oral squamous cell carcinoma. Pathology Research International 2013: 642496.

Hanlon, P., Avenell, A., Aucott, L. & Vickers, M.A. 2014. Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and systemic lupus erythematosus. Arthritis Research & Therapy 17(1): 274.

Jalouli, J., Ibrahim, S.O., Mehrotra, R., Jalouli, M.M., Sapkota, D., Larsson, P.A. & Hirsch, J.M. 2010. Prevalence of viral (HPV, EBV, HSV) infections in oral submucous fibrosis and oral cancer from India. Acta Oto-Laryngologica 130(11): 1306-1311.

Jayasooriya, S., De Silva, T.I., Njie-jobe, J., Sanyang, C., Leese, A.M., Bell, A.I., McAulay, K.A., Yanchun, P., Long, H.M. & Dong, T. 2015. Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children. PLoS Pathogens 11(3): e1004746.

Jenson, H.B. 2011. Epstein-Barr virus. Pediatrics in Review-Elk Grove 32(9): 375-383.

Kerishnan, J.P., Gopinath, S.C.B., Kai, S.B., Tang, T.H., Ng, H.L.C., Zainal Ariff, Abdul Rahman, Uda Hashim. & Chen, Y. 2016. Detection of human papillomavirus 16-specific IgG and IgM antibodies in patient sera: A potential indicator of oral squamous cell carcinoma risk factor. International Journal of Medical Sciences 13(6): 424-431.

Kumar, M., Nanavati, R., Modi, T.G. & Dobariya, C. 2016. Oral cancer: Etiology and risk factors: A review. Journal of Cancer Research and Therapeutics 12(2): 458-463.

Le Campion, A.C.O.V., Ribeiro, C.M.B., Luiz, R.R., da Silva Júnior, F.F., Barros, H.C.S., de Cássia Batista dos Santos, K., Ferreira, S.J., Gonçalves, L.S. & Ferreira, S.M.S. 2017. Low survival rates of oral and oropharyngeal squamous cell carcinoma. International Journal of Dentistry 2017: 5815493.

Litvinov, I.V., Shtreis, A., Kobayashi, K., Glassman, S., Tsang, M., Woetmann, A., Sasseville, D., Ødum, N. & Duvic, M. 2016. Investigating potential exogenous tumor initiating and promoting factors for cutaneous T-cell lymphomas (CTCL), a rare skin malignancy. Oncoimmunology 5(7): e1175799.

Macsween, K.F. & Johannessen, I. 2014. Epstein-barr virus (EBV): Infectious mononucleosis and other non-malignant EBV-associated diseases. In Viral Infections of Humans, edited by Kaslow, R., Stanberry, L. & Le Duc, J. Boston: Springer. pp. 867-896.

Mezher, M.N., Dakhil, A.S. & Abdul-Jawad, D.H. 2017. Role of Epstein-Barr virus (EBV) in human females with breast cancer. Journal of Pharmaceutical Sciences and Research 9(7): 1173-1177.

Mirzaei Habibollah, Hossein Goudarzi, Gita Eslami. & Ebrahim Faghihloo. 2018. Role of viruses in gastrointestinal cancer. Journal of Cellular Physiology 233(5): 4000-4014.

Odumade, O.A., Hogquist, K.A. & Balfour, H.H. 2011. Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clinical Microbiology Reviews 24(1): 193-209.

Patel, R. 2014. Epstein-Barr virus infections. In Sexually Transmitted Infections-E-book, edited by Gupta, S. & Kumar, B. New Delhi: Elsevier. p. 412.

Petter, A., Heim, K., Guger, M., Christensen, N., Sarcletti, M., Wieland, U., Pfister, H., Zangerle, R. & Höpfl, R. 2000. Specific serum IgG, IgM and IgA antibodies to human papillomavirus types 6, 11, 16, 18 and 31 virus-like particles in human immunodeficiency virus-seropositive women. Journal of General Virology 81(3): 701-708.

Polz-Gruszka, D., Macielag, P., Foltyn, S. & Polz-Dacewicz, M. 2014. Oral squamous cell carcinoma (OSCC)-molecular, viral and bacterial concepts. Journal of Pre-Clinical and Clinical Research doi: 10.5604/18982395.1135651.

Prabhu, S.R. & Wilson, D.F. 2016. Evidence of Epstein-Barr virus association with head and neck cancers: A review. J. Can. Dent. Assoc. 82(g2): 1488-2159.

Purushothaman, P. & Verma, S.C. 2014. Human DNA tumor viruses and oncogenesis. In Animal Biotechnology, edited by Verma, A.S. & Singh, A. Massachusetts: Academic Press. pp. 121-137.

Riordan, H.D., Riordan, N. & Neathery, M.T.S. 1996. Epstein- Barr Virus (EBV) infections in patients. The Journal of Orthomolecular Medicine 11(4): 208-210.

Rosnah Binti Zain, Vimmitra Athirajan, Wan Maria Nabillah Ghani, Ishak Abdul Razak, Raja Jalaludin Raja Latifah, Siti Mazlipah Ismail, Atiya Abdul Sallam, Anita Zarina Bustam, Zainal Ariff Abdul Rahman, Adam Hussien, Norain Talib, Sok Ching Cheong & Amin Jallaludin. 2013. An oral cancer biobank initiative: A platform for multidisciplinary research in a developing country. Cell and Tissue Banking 14(1): 45-52.

Rosnah Bte. Zain, Noriaki Ikeda, Prakash Chandra Gupta, Saman Warnakulasuriya, Christian Werner van Wyk, Prashanta Shrestha & Tony Axéll. 1999. Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: Consensus from a workshop held in Kuala Lumpur, Malaysia, November 25-27, 1996. J. Oral Pathol. Med. 28(1): 1-4.

Rugge, M., Fassan, M. & Graham, D.Y. 2015. Epidemiology of gastric cancer. In Gastric Cancer, edited by Strong, V. New York: Springer. pp. 23-34.

Salehi Hassan, Marziyeh Salehi, Rasoul Roghanian, Majid Bozari, Shirin Taleifard, Mohamad Mahdi Salehi. & Maryam Salehi. 2016. Comparison of serological and molecular test for diagnosis of infectious mononucleosis. Advanced Biomedical Research 5: 95.

Sand, L. & Jalouli, J. 2014. Viruses and oral cancer. Is there a link? Microbes and Infection 16(5): 371-378.

Sand, L.P., Jalouli, J., Larsson, P.A. & Hirsch, J.M. 2002. Prevalence of Epstein-Barr virus in oral squamous cell carcinoma, oral lichen planus, and normal oral mucosa. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 93(5): 586-592.

Scully, C. & Bagan, J.V. 2009. Oral squamous cell carcinoma: Overview of current understanding of aetiopathogenesis and clinical implications. Oral Diseases 15(6): 388-399.

She, Y., Nong, X., Zhang, M. & Wang, M. 2017. Epstein-Barr virus infection and oral squamous cell carcinoma risk: A meta-analysis. PloS ONE 12(10): e0186860.

Shimakage, M., Horii, K., Tempaku, A., Kakudo, K., Shirasaka, T. & Sasagawa, T. 2002. Association of Epstein-Barr virus with oral cancers. Human Pathology 33(6): 608-614.

Stamatiou, D.P., Derdas, S.P., Zoras, O.L. & Spandidos, D.A. 2016. Herpes and polyoma family viruses in thyroid cancer. Oncology Letters 11(3): 1635-1644.

Syrjänen, S., Lodi, G., von Bültzingslöwen, I., Aliko, A., Arduino, P., Campisi, G., Challacombe, S., Ficarra, G., Flaitz, C. & Zhou, H.M. 2011. Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: A systematic review. Oral Diseases 17(s1): 58-72.

Tang, Y.I., Liu, Y., Zhao, W., Yu, T. & Yu, H. 2015. Caspase-8 polymorphisms and risk of oral squamous cell carcinoma. Experimental and Therapeutic Medicine 10(6): 2267-2276.

Thompson, M.P. & Kurzrock, R. 2004. Epstein-Barr virus and cancer. Clinical Cancer Research 10(3): 803-821.

Wang, S., Xiong, H., Yan, S., Wu, N. & Lu, Z. 2016. Identification and characterization of Epstein-Barr virus genomes in lung carcinoma biopsy samples by next-generation sequencing technology. Scientific Reports 6: 26156.

Yen, C.Y., Lu, M.C., Tzeng, C.C., Huang, J.Y., Chang, H.W., Chen, R.S., Liu, S.Y., Liu, S.T., Shieh, B. & Li, C. 2009. Detection of EBV infection and gene expression in oral cancer from patients in Taiwan by microarray analysis. BioMed Research International 2009: 904589.

*Corresponding author; email: chenyeng@um.edu.my