Epstein-Barr virus predominance and immunological abnormalities in oral squamous cell carcinoma


  • Ahmed Talib Ghadhban
  • Marwa Mohammed Ali Jassim
  • Majid Mohammed Mahmood




oral squamous cell carcinoma, Epstein-Barr virus, in situ hybridization, EBNA, IL-10


BACKGROUND: Both benign and harmful head and neck disorders have been associated with the Epstein-Barr virus (EBV). Many studies have connected EBV to oral squamous cell carcinoma (OSCC). Oral squamous cell carcinoma is the most prevalent type of cancer. Fresh tissue samples from patients with OSCC were tested for the presence of Epstein-Barr virus.

OBJECTIVE: To determine the frequency of EBV and IL10 expression in OSCC patients.

MATERIALS AND METHODS: Fifty individuals with OSCC and 25 with clinically healthy oral mucosa were studied. In situ hybridization was used for the detection of EBV. Serum IL-10 levels were also evaluated in patients and controls using a human IL-10 ELISA Kit.

RESULTS: EBV was detected in 4 healthy patients, 6 with moderately differentiated OSCC, 10 with poorly differentiated OSCC, and 19 with undifferentiated OSCC. These differences were statistically significant (p<0.05). IL-10 expression was more common in OSCC diagnostic groups than healthy controls, and the difference in blood IL-10 levels between patients and controls was statistically significant (p<0.01).

CONCLUSION: The prevalence of EBV in OSCC suggests its possible role in oral cavity malignancy. On the other hand, IL-10 is expressed at higher levels in OSCC biopsies; such elevated concentrations may promote viral spread.

Author Biographies

Ahmed Talib Ghadhban

College of Dentistry, Al-Muthanna University, Al-Muthanna, Iraq

Marwa Mohammed Ali Jassim

College of Dentistry, Al-Muthanna University, Al-Muthanna, Iraq

Majid Mohammed Mahmood

Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq


Pennacchiotti G, Álvarez C, Montes R, Cárcamo M, Sáez R, Martínez MJ. Epstein-Barr Virus in Oral Cavity Squamous Cell Carcinoma of Chilean Patients. Int J Oral Dent Health. 2020;6:106.

Anwar N, Pervez S, Chundriger Q, Awan S, Moatter T, Ali TS. Oral cancer: Clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in Pakistan. Plos one. 2020;15(8):e0236359.

Alvarez Amézaga J, Barbier Herrero L, Pijoan del Barrio JI, Martín Rodríguez JC, Romo Simón L, Genolla Subirats J, Rios Altolaguirre G, Ríos AD, Arteagoitia Calvo I, Landa Llona S, Arruti González JA. Diagnostic efficacy of sentinel node biopsy in oral squamous cell carcinoma: Cohort study and meta-analysis. Medicina Oral, Patología Oral y Cirugía Bucal (Internet). 2007;12(3):235-43.

Museedi OS, Younis WH. Oral cancer trends in Iraq from 2000 to 2008. The Saudi Journal for Dental Research. 2014 ;5(1):41-7.

Al-Rawi N, Talabani N. Squamous cell carcinoma of the oral cavity: a case series analysis of clinical presentation and histological grading of 1425 cases from Iraq. Clin Oral Investig. 2008;12(1):15–8.

Al-Mahfoud M, AlSaimary I, Al SA. Occurrence of oral and oropharyngeal squamous cell carcinoma among patients in Basrah city. Iraqi J Biotechnol. 2017;16(3):255–61.

Khudier H. Malignant oral lesions in Sulaimania governorate/ a (5 years) retrospective study. Diyala J Med. 2012;2(1):13–20.

Al-Niaimi AI. Oral malignant lesions in a sample of patients in the north of Iraq (Retrospective study). Al–Rafidain Dent J. 2006; 6(2): 176–180.

Fuoad SA, Mohammad DN, Hamied MA, Garib BT. Oro-facial malignancy in north of Iraq: a retrospective study of biopsied cases. BMC Oral Health. 2021;21:1-0.

Mohammed M. The retrospective survey of oral and maxillofacial malignant neoplasms. MDJ. 2014;11(1):129–35.

Aljazaeri S, Al Qudsi G, Jaber H, Al Elwi W, Haddad S, Echrish H. Biopsy records to the oral lesions in Basrah between 2012–2017. J Oral Med Oral Surg Oral Pathol Oral Radiol. 2020;6(2):74–80.

Basha S, Mohamed R, Al-Thomali Y, Al SA. The prevalence of oral cancer in Saudi Arabia—a systematic review. Ann Med Health Sci Res. 2019;9(2):553–7.

Zaccone R, Renzi A, Chalfon C, Lenzi J, Bellei E, Marconato L, Ros E, Rigillo A, Bettini G, Faroni E, Guerra D. Environmental risk factors for the development of oral squamous cell carcinoma in cats. Journal of Veterinary Internal Medicine. 2022;36(4):1398-408.

Bakkalci D, Jia Y, Winter JR, Lewis JE, Taylor GS, Stagg HR. Risk factors for Epstein Barr virus-associated cancers: a systematic review, critical appraisal, and mapping of the epidemiological evidence. Journal of global health. 2020;10(1).

Brouwer L, Moreni G, Wolthers KC, Pajkrt D. World-wide prevalence and genotype distribution of enteroviruses. Viruses. 2021;13(3):434.

Yu X, He S, Shen J, Huang Q, Yang P, Huang L, Pu D, Wang L, Li L, Liu J, Liu Z. Tumor vessel normalization and immunotherapy in gastric cancer. Therapeutic Advances in Medical Oncology. 2022;14:17588359221110176.

da Silva RR, Vasconcelos FD, Tavares DD, Dos Santos PL. Association between interleukin 10 (IL-10) polymorphisms and leishmaniasis progression: a systematic review and meta-analysis. Scientific Reports. 2022 ; 12(1):11136.

Caruntu A, Scheau C, Codrici E, Popescu ID, Calenic B, Caruntu C, Tanase C. The assessment of serum cytokines in oral squamous cell carcinoma patients: An observational prospective controlled study. Journal of Clinical Medicine. 2022 ;11(18):5398.

Xiao L, Li X, Cao P, Fei W, Zhou H, Tang N, Liu Y. Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway. Journal of Experimental & Clinical Cancer Research. 2022;41(1):166.

Meng C, Zhao X, Lao J. A modified immunofluorescence in situ hybridization method to detect long non coding RNAs and proteins in frozen spinal cord sections. Experimental and Therapeutic Medicine. 2018;15(6):4623-8.

Hoffmann TK, Sonkoly E, Homey B, Scheckenbach K, Gwosdz C, Bas M, Chaker A, Schirlau K, Whiteside TL. Aberrant cytokine expression in serum of patients with adenoid cystic carcinoma and squamous cell carcinoma of the head and neck. Head & Neck: Journal for the Sciences and Specialties of the Head and Neck. 2007;29(5):472-8.

Gaiolla RD, Domingues MA, Niéro-Melo L, De Oliveira DE. Serum levels of interleukins 6, 10, and 13 before and after treatment of classic Hodgkin lymphoma. Archives of pathology & laboratory medicine. 2011;135(4):483-9.

Ali MN, Omar TA, El Sheikh SM, Swaify GA, Fayad AI. Expression of interleukin-10 and its value as a potential marker in oral squamous cell carcinoma. Alexandria Dental Journal. 2018 ;43(1):11-6.

Hamzavi M, Tadbir AA, Rezvani G, Ashraf MJ, Fattahi MJ, Khademi B, Sardari Y, Jeirudi N. Tissue expression, serum and salivary levels of IL-10 in patients with head and neck squamous cell carcinoma. Asian Pacific Journal of Cancer Prevention. 2013;14(3):1681-5.

Nelson EL, Wenzel LB, Osann K, Dogan-Ates A, Chantana N, Reina-Patton A, Laust AK, Nishimoto KP, Chicz-DeMet A, du Pont N, Monk BJ. Stress, immunity, and cervical cancer: biobehavioral outcomes of a randomized clinical trail. Clinical cancer research. 2008 ;14(7):2111-8.

Aziz S, Ahmed SS, Ali A, Khan FA, Zulfiqar G, Iqbal J, Khan AA, Shoaib M. Salivary immunosuppressive cytokines IL-10 and IL-13 are significantly elevated in oral squamous cell carcinoma patients. Cancer investigation. 2015;33(7):318-28.

Szabo YZ, Newton TL, Miller JJ, Lyle KB, Fernandez-Botran R. Acute stress induces increases in salivary IL-10 levels. Stress. 2016;19(5):499-505.

Cruz I, Van den Brule AJ, Steenbergen RD, Snijders PJ, Meijer CJ, Walboomers JM, Snow GB, Van der Waal I. Prevalence of Epstein—Barr virus in oral squamous cell carcinomas, premalignant lesions and normal mucosa—a study using the polymerase chain reaction. Oral oncology. 1997 ;33(3):182-8.






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