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 RAMANATHAN2,3, 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
Diserahkan:
9 Februari 2019/Diterima: 11 Jun 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
RUJUKAN
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.
*Pengarang
untuk surat-menyurat; email: chenyeng@um.edu.my
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