Background: Cervical cancer (CC) ranks third among all malignant diseases of the female reproductive system. CC arises through a series of pathological changes called cervical intraepithelial neoplasia (CIN). Timely diagnosis and treatment of CIN are essential in the prevention of CC. Oxidative stress (OS) presents a major risk factor in the pathogenesis of both CC and CIN. This study aimed to determine the association between OS and the pathohistological severity of cervical lesions.

Materials and Methods: The research was conducted at the Clinical Center of the University of Sarajevo on 240 female respondents divided into two groups. The experimental group consisted of 200 women with changes consistent with CIN, carcinoma in situ (CIS), and CC determined by biopsy, divided into 5 subgroups (CIN 1, CIN 2, CIN 3, CIS, and CC) with 40 respondents per group. The control group (N=40) had biopsy findings that were non-pathological. The concentration of acid thiobarbituric reactive substances (TBARS) was determined for all subjects from bioptic samples using the spectrophotometric method and according to standard laboratory practice.

Results: Our results showed a significant difference in age between patients with CIN 1, CIN 2, and CIN 3 and the control group as well as when compared to patients with CC. The oldest group comprised patients with CC. Tissue TBARS levels in the CIS group were significantly higher than that of the control group (p<0.001), CIN 1 group (p<0.001), CIN 2 group (p<0.001), CIN 3 group (p=0.033), as well as CC group (p=0.002). Likewise, tissue TBARS levels in the CIN 3 group were significantly higher than those of the control group (p=0.023), and CIN 1 group (p=0.024).

Conclusion: Compared to healthy controls, patients with CIN and CC have increased oxidative stress. Tissue TBARS levels represent a significant differentiation marker of the clinical stage of the disease and can be a useful diagnostic tool influencing the selection of therapeutic procedures.

 

oxidative stress, cervical intraepithelial neoplasia, cervical cancer

 

1. Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191-e203. doi: 10.1016/S2214-109X(19)30482-6.
2. Lukac A, Sulovic N, Smiljic S, Ilic AN, Saban O. The prevalence of the most important risk factors associated with cervical cancer. Mater Sociomed. 2018;30(2):131-5. doi: 10.5455/msm.2018.30.131-135.
3. Wang Z, Wang J, Fan J, Zhao W, Yang X, Wu L, et al. Risk factors for cervical intraepithelial neoplasia and cervical cancer in Chinese women: large study in Jiexiu, Shanxi Province, China. J Cancer. 2017;8(6):924-32. doi: 10.7150/jca.17416.
4. Basoya S, Anjankar A. Cervical cancer: early detection and prevention in reproductive age group. Cureus. 2022;14(11):e31312. doi: 10.7759/cureus.31312.
5. Anfinan N, Sait K. Indicators of survival and prognostic factors in women treated for cervical cancer at a tertiary care center in Saudi Arabia. Ann Saudi Med. 2020;40(1):25-35. doi: 10.5144/0256-4947.2020.25.
6. Jeong SY, Park H, Kim MS, Kang JH, Paik ES, Lee YY, et al. Pretreatment lymph node metastasis as a prognostic significance in cervical cancer: comparison between disease status. Cancer Res Treat. 2020;52(2):516-23. doi: 10.4143/crt.2019.328.
7. Zahra K, Patel S, Dey T, Pandey U, Mishra SP. A study of oxidative stress in cervical cancer- an institutional study. Biochem Biophys Rep. 2020;25:100881. doi: 10.1016/j.bbrep.2020.100881.
8. Manokaran K, Bhat P, Nayak D, Baskaran R, Paramasivam P, Ahmed SF, et al. Oxidative stress and female reproductive disorder: A review. Asian Pacific Journal of Reproduction.2022; 11(3):107-16. doi: 10.4103/2305-0500.346088.
9. Chang HK, Seo SS, Myong JP, Yu YL, Byun SW. Incidence and costs of cervical intraepithelial neoplasia in the Korean population. J Gynecol Oncol. 2019;30(3):e37. doi: 10.3802/jgo.2019.30.e37.
10. Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol. 2012;2012:137289. doi: 10.5402/2012/137289.
11. Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol. 2010;38(1):96-109. doi: 10.1177/0192623309356453.
12. Lepara Z, Lepara O, Fajkić A, Rebić D, Alić J, Spahović H. Serum malondialdehyde (MDA) level as a potential biomarker of cancer progression for patients with bladder cancer. Rom J Intern Med. 2020;58(3):146-52. doi: 10.2478/rjim-2020-0008.
13. Klaunig JE. Oxidative stress and cancer. Curr Pharm Des. 2018;24(40):4771-8. doi: 10.2174/1381612825666190215121712.
14. Calaf GM, Urzua U, Termini L, Aguayo F. Oxidative stress in female cancers. Oncotarget. 2018;9(34):23824-42. doi: 10.18632/oncotarget.25323.
15. Jelić M, Mandić A, Kladar N, Sudji J, Božin B, Srdjenović B. Lipid peroxidation, antioxidative defense and level of 8-hydroxy-2-deoxyguanosine in cervical cancer patients. J Med Biochem. 2018;37(3):336-45. doi: 10.1515/jomb-2017-0053.
16. Srivastava S, Natu SM, Gupta A, Pal KA, Singh U, Agarwal GG, et al. Lipid peroxidation and antioxidants in different stages of cervical cancer: prognostic significance. Indian J Cancer. 2009;46(4):297-302. doi: 10.4103/0019-509X.55549.
17. Carrero Y, Callejas D, Alaña F, Silva C, Mindiola R, Mosquera J. Increased vascular endothelial growth factor expression, CD3-positive cell infiltration, and oxidative stress in premalignant lesions of the cervix. Cancer. 2009;115(16):3680-8. doi: 10.1002/cncr.24411.
18. Jelic MD, Mandic AD, Maricic SM, Srdjenovic BU. Oxidative stress and its role in cancer. J Cancer Res Ther. 2021;17(1):22-8. doi: 10.4103/jcrt.JCRT_862_16.
19. Visalli G, Riso R, Facciolà A, Mondello P, Caruso C, Picerno I, et al. Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection. J Med Virol. 2016;88(2):336-44. doi: 10.1002/jmv.24327.
20. Carneiro SR, da Silva Lima AA, de Fátima Silva Santos G, de Oliveira CSB, Almeida MCV, da Conceição Nascimento Pinheiro M. Relationship between oxidative stress and physical activity in women with squamous intraepithelial lesions in a cervical cancer control program in the Brazilian Amazon. Oxid Med Cell Longev. 2019;2019:8909852. doi: 10.1155/2019/8909852.
21. Shah S, Kalal BS. Oxidative stress in cervical cancer and its response to chemoradiation. Turk J Obstet Gynecol. 2019;16(2):124-8. doi: 10.4274/tjod.galenos.2019.19577.
22. Asotic A. The role of oxidative stress in the development of cervical intraepithelial neoplasia and invasive cervical cancer [PhD Dissertation]. [Banja Luka]:Faculty of Medicine, University of Banja Luka;2022.105 p. Available from https://fedora.unibl.org/fedora/get/o:2463/bdef:Content/get