Tayup ŞİMŞEK, Serap FIRTINA TUNCER, Özer BİRGE, Hasan Aykut TUNCER, İkbal ÖZEN KÜCÜKÇETİN

Düşük ve Yüksek Dereceli Servikal Preinvaziv Lezyonlarda Serum Dinamik Tiyol/Disülfid Oranlarının Karşılaştırılması

Amaç: Serviks kanseri, Human Papilloma Virüs HPV enfeksiyonuna bağlı gelişir. Servikal premalign lezyonların serviks kanserine progresyonunda oksidatif stresin rol aldığı düşünülmektedir. Biz bu çalışmamızda düşük ve yüksek dereceli servikal preinvaziv lezyonlarda serum dinamik tiyol/disülfid oranlarını karşılaştırmayı amaçladık. Gereç ve Yöntemler: HPV test sonucu elde edilen 132 hasta prospektif kohort çalışma kapsamında değerlendirildi. Tüm hastalarda serum total ve doğal tiyol, dinamik disülfid, azaltılmış ve oksitlenmiş tiyol oranları ve tiyol oksidasyon-indirgeme oranı ölçüldü. Hastalar kolposkopik biyopsi, endoservikal örnekleme veya Loop elektrocerrahi eksizyon prosedürü patoloji raporlarındaki en yüksek dereceli servikal intraepithelial neoplazi CIN ya da serviks kanseri sonuçlarına göre ≤CIN 1 ve ≥CIN 2 olarak iki gruba ayrılarak, demografik, klinik ve dinamik tiyol/disülfid hemostazı parametreleri karşılaştırıldı.Bulgular: CIN 2 lezyonlar 42 %31,8 hastada saptanırken 1 hasta serviks kanseri tanısı aldı. ≤CIN 1 ve ≥CIN 2 grupları arasında dinamik tiyol/disülfid hemostazı parametrelerinin benzer olduğu görüldü. Yüksek riskli HPV Hr-HPV taşıyıcılığının ≥CIN 2 grubunda, ≤CIN 1 grubuna göre belirgin olarak fazla olduğu görüldü %39 vs %12,5, p=0,005 . Sonuç: Düşük ve yüksek dereceli servikal preinvaziv lezyonların serum dinamik tiyol/disülfid oranları arasında fark bulunmamaktadır. ≤CIN 1 ve ≥CIN 2 hastaların ayrımında belirgin tek faktör Hr-HPV taşıyıcılığıdır

Anahtar Kelimeler:

Oksidatif stres, Tiyol/Disülfid homeostazı, Human papilloma virüs, Premalign lezyon, Serviks kanseri

Comparison of Serum Dynamic Thiol/Disulfide Ratios in Low and High Grade Cervical Preinvasive Lesions

Objective: Cervical cancer develops due to the Human Papilloma Virus HPV infection. Oxidative stress is thought to play a role in cervical premalignant lesions’ evolving to cervical cancer. This study aims at comparing serum dynamic thiol/disulfide ratios in low and high grade cervical preinvasive lesions. Material and Methods: One hundred thirty-two patients diagnosed with HPV as a result of tests were evaluated within the scope of prospective cohort study. Serum total and natural thiol, dynamic disulfide, reduced and oxidized thiol ratios, and the thiol oxidation-reduction ratios were measured in all patients. The patients were divided into 2 groups as ≤CIN 1 and ≥CIN 2. This has been done on the basis of the highest grade of cervical intraepithelial neoplasia CIN or cervical cancer results on colposcopic biopsy, endocervical sampling, as well as the Loop electrosurgical excision procedure. Demographic, clinical and dynamic thiol/disulfide homeostasis parameters were compared between the 2 groups. Results: While CIN 2 lesions were detected in 42 31.8% patients, 1 patient was diagnosed with cervical cancer. Dynamic thiol/disulfide homeostasis parameters were similar between the ≤CIN 1 and ≥CIN 2 groups. High-risk HPV Hr-HPV positivity was remarkably higher in ≥CIN 2 patients compared to ≤CIN 1 patients 39% vs. 12.5%, p=0.005 . Conclusion: There is no difference between the serum dynamic thiol/disulfide ratios of low grade and high grade cervical preinvasive lesions. Hr-HPV is the only marker in differentiating ≤CIN 1 and ≥CIN 2 patients

Keywords:

Oxidative Stress, Thiol/disulfide homeostasis, Human papilloma virus, Premalignant lesion, Cervical cancer,

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Cruz Gregorio A, Manzo Merino J, Lizano M. Cellular redox, cancer and human papillomavirus. Virus Res 2018; 246:35-45.
Hudelist G, Manavi M, Pischinger KI, Watkins-Riedel T, Singer CF, Kubista E, Czerwenka KF. Physical state and expression of HPV DNA in benign and dysplastic cervical tissue: different levels of viral integration are correlated with lesion grade. Gynecol Oncol 2004; 92:873-80.
Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, Snijders PJ, Meijer CJ. International Agency for Research on Cancer Multicenter Cervical Cancer Study Group: Epidemiologic classification of human papilloma virus types associated with cervical cancer. N Engl J Med 2003; 348:518-27.
Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990; 63:1129-36.
Cripe TP, Haugen TH, Turk JP, Tabatabai F, Schmid PG, Durst M, Gissmann L, Roman A, Turek LP. Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte- dependent enhancer, and by viral E2 trans-activator and repressor gene products: Implications for cervical carcinogenesis. EMBO J 1987; 6:3745-53.
Cullen AP, Reid R, Campion M, Lorincz AT. Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. J Virol 1991; 65:606-12.
Pirami L, Giache V, Becciolini A. Analysis of HPV16, 18, 31, and 35 DNA in pre-invasive and invasive lesions of the uterine cervix. J Clin Pathol 1997;50:600-4.
Beerheide W, Sim MM, Tan YJ, Bernard HU, Ting AE. Inactivation of the human papillomavirus-16 E6 oncoprotein by organic disulfides. Bioorg Med Chem 2000; 8:2549-60.
Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014;47:326- 32.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189:12-9.
Mogensen O. Improvement of women’s health-HPV vaccination after 16 years of age? Acta Obstet Gynecol Scand 2009; 88:756-7.
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420:860-7.
Bartsch H, Nair J. Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: Role of lipid peroxidation, DNA damage, and repair. Langenbecks Arch Surg 2006; 391:499-510.
Foppoli C, De Marco F, Cini C, Perluigi M. Redox control of viral carcinogenesis: The human papillomavirus paradigm. Biochim Biophys Acta 2015; 1850:1622-32.
Stanley M. HPV - immune response to infection and vaccination. Infect Agent Cancer 2010; 5:19.
De Marco F. Oxidative stress and HPV carcinogenesis. Viruses 2013; 5:708-31.
De Marco F, Bucaj E, Foppoli C, Fiorini A, Blarzino C, Filipi K, Giorgi A, Schininà ME, Di Domenico F, Coccia R, Butterfield DA, Perluigi M. Oxidative stress in HPV-driven viral carcinogenesis: Redox proteomics analysis of HPV-16 dysplastic and neoplastic tissues. PLoS One 2012; 7:e34366.
Senapati R, Senapati NN, Dwibedi B. Molecular mechanisms of HPV mediated neoplastic progression. Infect Agent Cancer 2016; 11:59.
Butterfield DA. Keller JN. Antioxidants and antioxidant treatment in disease. Biochem Biophys Acta 2012; 1822:615.
Butterfield DA. Oxidative stress in neurodegenerative disorders. Antioxid Redox Signal 2006; 2006:1971-3.