The role of oxidative stress in cancer associated with viral infection
More details
Hide details
Department of Virology, Medical University of Lublin, Poland
Chair and Department of Conservative Dentistry with Endodontics, Medical University of Lublin, Poland
Corresponding author
Ewa Kliszczewska   

Department of Virology, Medical University of Lublin, Al. Racławickie 1, 20-059 Lublin, Poland
J Pre Clin Clin Res. 2018;12(2):41-44
The role of oxidative stress in the pathogenesis of neoplastic diseases, including its connection with viral infections, is the subject of many publications. The results of numerous researches have revealed that virus-induced phagocyte activation is associated with oxidative stress, not only because reactive oxygen species (ROS) are released, but also because activated phagocytes can release cytokines, such as tumour necrosis factor (TNF-alpha) or interleukin-1 (IL-1).

The purpose of this review is to analyze the role of ROS in the pathogenesis of head and neck cancer and correlation between ROS and viruses, especially Epstein-Barr virus (EBV) and Human papillomavirus (HPV), in malignant tumour development in this area.

State of knowledge:
The effects of an increased amount of ROS or reactive nitrate species (RNS) with a simultaneous reduction of antioxidants are noticed in various cancers, including head and neck cancer. Increased oxidative stress is also associated with disorders in the antioxidant defence system. HPV and EBV, which are important risk factors for head and neck cancer, can act via ROS-based mechanisms. Long-term expression of the Epstein–Barr nuclear antigen 1 (EBNA1) causes increased ROS and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase level. During expression of HPV16- infected cells, RNS increase E6 and E7 levels, thereby increasing the level of DNA damage in the cell. ROS are also involved in many benign oral disorders.

Reactive oxygen species are involved in various pathological processes in the environment of chronic oxidative stress, including carcinogenicity. ROS contribute to the development of head and neck cancer through many risk factors, such as connection with viruses.

Karpińska A, Gromadzka G. Oxidative stress and natural antioxidant mechanisms: the role in neurodegeneration. From molecular mechanisms to therapeutic strategies. Postepy Hig Med Dosw. 2013; 67: 43–53. In Polish.
Bert P. La Pression barometrique, Libraire de l’Acad de Med. 1878; Paris.Kulbacka J, Saczko J, Chwiłkowska A. Oxidative stress in cells damage processes. Pol. Merk. Lek. 2009; XXVII, 157, 44. In Polish.
Ścibior-Bentkowska D, Czeczot H. Cancer cells and oxidative stress. Postepy Hig Med Dosw. (online). 2009; 63: 58–72. In Polish.
Choudhari SK, Chaudhary M, Gadbail AR, Sharma A, Tekade S. Oxidative and antioxidative mechanisms in oral cancer and precancer: a review. Oral Oncol. 2014; 50(1): 10–8.
Sharma S, Shrivastav A, Shrivastav BR. Clinical evidences of oxidative stress as biomarker in various types of cancers: A review. IJPSR. 2014; 5(3): 657–665.
Katakwar P, Metgud R, Naik S, Mittal R. Oxidative stress marker in oral cancer: A review. J Cancer Res Ther. 2016; 12(2): 438–46.
Trueba GP, Sánchez GM, Giuliani A. Oxygen free radical and antioxidant defence mechanism in cancer. Front Biosci. 2004; 9: 2029–2044.
Fuchs-Tarlovsky V. Role of antioxidants in cancer therapy. Nutrition. 2013; 29(1):15–21.
Mascolo M, Siano M, Ilardi G, Russo D, Merolla F, De Rosa G, et al. Epigenetic Disregulation in Oral Cancer. Int J Mol Sci. 2012; 13(2): 2331–2353.
Polz-Gruszka D, Macieląg P, Fołtyn S, Polz-Dacewicz M. Oral squamous cell carcinoma (OSCC) – molecular, viral and bacterial concepts. J Pre-Clin Clin Res. 2014; 8(2): 61–66.
Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted.
Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2017, 3(4), 524–548.
Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston- Martin S, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res. 1988; 48(11): 3282–3287.
Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008; 100(4): 261–269.
Hillbertz NS, Hirsch JM, Jalouli J, Jalouli MM, Sand L. Viral and molecular aspects of oral cancer. Anticancer Res. 2012; 32(10): 4201– 4212.
Kesarwala AH, Krishna MC, Mitchell JB. Oxidative stress in oral diseases. Oral Dis. 2016; 22(1): 9–18.
Konopka T, Gmyrek−Marciniak A, Kozłowski Z, Kaczmarek U, Wnukiewicz J. Antioxidant Capacity of Saliva in Patients with Periodontitis and Squamous Carcinoma of the Mouth Floor. Dent Med Probl. 2006; 43(3): 354–362. In Polish.
Metgud R, Astekar M, Verma M, Sharma A. Role of viruses in oral squamous cell carcinoma. Oncol Rev. 2012; 6(2): e21.
Sand L, Jalouli J. Viruses and oral cancer. Is there a link? Microbes Infect. 2014; 16(5): 371–378.
Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000; 92(9): 709–720.
Scully C. Oral cancer aetiopathogenesis; past, present and future aspects. Medicina Oral Patologia Oral Y Cirugia Bucal. 2011; 16(3): e306–e311.
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. International Agency for Research on Cancer: Lyon, France. 2007; pp. 222–230.
Acharya S, Ekalaksananan T, Vatanasapt P, Loyha K, Phusingha P, Promthet S, et al. Association of Epstein-Barr virus infection with oral squamous cell carcinoma in a case-control study. J Oral Pathol Med. 2005; 44(4): 252–257.
Jalouli J, Ibrahim SO, Mehrotra R, Jalouli MM, Sapkota D, Larson PA, et al. Prevalence of viral (HPV, EBV, HSV) infections in oral submucous fibrosis and oral cancer from India. Acta Otolaryngol. 2010; 130(11): 1306–1311.
Jalouli J, Jalouli MM, Sapkota D, Ibrahim SO, Larson PA, Sand L. Human papilloma virus, herpes simplex and Epstein-Barr virus in oral squamous cell carcinoma from eight different countries. Anticancer Res. 2012; 32(2): 571–580.
Cao JY, Mansouri S, Frappier L. Changes in the nasopharyn-geal carcinoma nuclear proteome induced by the EBNA1 protein of Epstein– Barr virus reveal potential roles for EBNA1 in metas-tasis and oxidative stress responses. J Virol. 2012; 86(1): 382–394.
Williams VM, Filippova M, Filippov V, Payne KJ, Duerksen-Hughes P. Human papillomavirus type 16 E6* induces oxidative stress and DNA damage. J Virol. 2014; 88(12): 6751–6761.
Radhashree M. Viruses and Head and Neck Cancers. Head and Cancer Research. 2015; 1(1): 3.
Wei L, Gravitt PE, Song H, Maldonado AM, Ozbun MA. Nitric oxide induces early viral transcription coincident with increased DNA damage and mutation rates in human papillomavirus-infected cells. Cancer Res. 2009; 69(11): 4878–4884.
Williams VM, Filippova M, Soto U, Duerksen-Hughes PJ. HPV-DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virol. 2011; 6(1): 45–57.
Lai D, Tan CL, Gunaratne J, Quek LS, Nei W, Thierry F, et al. Localization of HPV-18 E2 at mitochondrial membranes induces ROS release and modulates host cell metabolism. PLoS ONE. 2013; 8(9): e75625.
Journals System - logo
Scroll to top