Strong SOD2 expression and HPV-16/18 positivity are independent events in cervical cancer

// Silvia Helena Rabelo-Santos 1 , Lara Termini 2 , Enrique Boccardo 3 , Sophie Derchain 4 , Adhemar Longatto-Filho 5, 6 , Maria Antonieta Andreoli 7 , Maria Cecilia Costa 2 , Rafaella Almeida Lima Nunes 2 , Liliana Aparecida Lucci Ângelo-Andrade 8 , Luisa Lina Villa 2, 9 and Luiz Carlos Zeferino 4 1 School of Pharmacy, Federal University of Goias (UFG – Universidade Federal de Goias), Goias, Brazil 2 Innovation in Cancer Laboratory, Center of Translational Research in Oncology, Cancer Institute of Sao Paulo (ICESP - Instituto do Câncer do Estado de Sao Paulo), Faculty of Medicine of University of Sao Paulo (FMUSP - Faculdade de Medicina da Universidade de Sao Paulo), Sao Paulo, Sao Paulo, Brazil 3 Laboratory of Oncovirology, Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo (USP - Universidade de Sao Paulo), Sao Paulo, Sao Paulo, Brazil 4 Department of Obstetrics and Gynecololy, State University of Campinas (UNICAMP – Universidade Estadual de Campinas), Campinas, Sao Paulo, Brazil 5 Laboratory of Medical Research, Faculty of Medicine of University of Sao Paulo (Faculdade de Medicina da Universidade de Sao Paulo-FMUSP), Sao Paulo, Sao Paulo, Brazil 6 Institute of Life Sciences and Health, Faculty of Health Sciences, (ICVS), University of Minho, Braga, Portugal. 7 International Research Center, A.C. Camargo Cancer Center, Sao Paulo, Sao Paulo, Brazil 8 Department of Pathology, State University of Campinas (UNICAMP – Universidade Estadual de Campinas), Campinas, Sao Paulo, Brazil 9 Department of Radiology and Oncology, Faculty of Medicine of University of Sao Paulo (FMUSP - Faculdade de Medicina da Universidade de Sao Paulo-USP), Sao Paulo, Sao Paulo, Brazil Correspondence to: Luiz Carlos Zeferino, email: zeferino@fcm.unicamp.br Keywords: human papillomavirus; cervical intraepithelial neoplasia; squamous cell carcinoma; adenocarcinoma; superoxide dismutase-2; Pathology Received: June 19, 2017      Accepted: March 11, 2018      Published: April 24, 2018 ABSTRACT It is well known that persistent infection with high-risk HPV (hr-HPV), mostly HPV-16 and 18, is the main cause of cervical cancer development. Manganese superoxide dismutase (MnSOD or SOD2) are highly expressed in different neoplasia. The present study investigated SOD2 protein expression and the presence of hr-HPV types in 297 cervical samples including non-neoplastic tissue, cervical intraepithelial neoplasia grade 3 (CIN3), squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Strong SOD2 expression was significantly higher in ADC (82%) than CIN3 (52%) or SCC (64%). There was no association between SOD2 expression and HPV 16 and/or 18 detection for every lesion analyzed. Binary Logist Regression revealed that strong SOD2 expression (OR: 27.50, 6.16-122.81) and HPV 16 and/or HPV 18 (OR: 12.67, 4.04-39.74) were independently more associated with CIN3 than non-neoplastic cervix. Strong SOD2 expression (OR: 3.30, 1.23-8.86) and HPV 16 and/or HPV 18 (OR: 3.51, 1.03-11.87) were independently more associated with ADC than SCC. Similar findings for SOD2 expression were observed by the Cochran Mantel-Haenszel test, controlling for HPV-16 and/or HPV 18. In conclusion, the expression of SOD2 was increased in CIN3 and SCC, and more increased in cervical ADC than in SCC. Strong SOD2 expression was statistically independent of the presence of HPV 16 and/or 18. These findings suggest that the mitochondrial antioxidant system and HPV infection could follow independent pathways in the carcinogenesis of cervical epithelium and in the differentiation to SCC or ADC of the cervix.