HPV infection associated DNA damage correlated with cervical precancerous lesions and cancer in the highest area of cervical cancer mortality, Longnan, China
Received 14 January 2019
Accepted for publication 27 June 2019
Published 30 July 2019 Volume 2019:11 Pages 7197—7210
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Professor Nakshatri
Jin Zhao,1,* Zhong Guo,1,* Qiang Wang,2 Tianbin Si,3 Shuyan Pei,1 Hongmei Qu,1 Lina Shang,1 Yuqing Yang,1 Lili Wang1
1Department of Medical Function, Medical College of Northwest Minzu University, Lanzhou 730030, People’s Republic of China; 2Department of Pathology, No. 1 Hospital of Longnan City, Longnan 746000, People’s Republic of China; 3Department of Gynecology and Oncology, Gansu Provincial Cancer Hospital, Lanzhou 730050, People’s Republic of China
*These authors contributed equally to this work
Objectives: This study was to assess whether human papillomavirus (HPV) resulting in genetic instability is one reason for the high incidence and mortality of cervical cancer in Longnan.
Methods: Between 2012 and 2016, a total of 346 samples from Longnan were collected and divided into four groups: cervicitis group (n=57), cervical intraepithelial neoplasia I group (CIN I, n=63), CIN II/III group (n=79) and invasive squamous cell carcinoma group (SCC, n=147). HPV E6/E7 mRNA was detected by Quantivirus® HPV E6/E7 RNA 3.0 assay (bDNA). The markers of DNA damage response (DDR) – ataxia telangiectasia mutated (ATM) pSer1981, H2AX pSer139 (γH2AX), Chk2 pThr68 and P53 – were analyzed by immunohistochemistry.
Results: The activation of ATM, γH2AX, Chk2 and P53 was increased with increasing severity of cervical lesion. A significant difference of ATM expression in simple infection was also shown accompanied by the cervical lesion. The expression of γH2AX between HPV16+ and HPV16- specimens, γH2AX and P53 between HPV58+ and HPV58- groups had statistical significance. The expression and copy number of HPV E6/7 mRNA increases with the cervical lesion severity. A significant difference was shown for P53 expression between HPV E6/7 mRNA+ and mRNA- specimens. A close correlation with CHK2 expression for HPV E6/7 mRNA+ and HPV16 E6/7 mRNA+ specimens and γH2AX and CHK2 expression for SCC specimens was shown between low and high viral load groups.
Conclusions: DDR, HPV genotypes and HPV E6/E7 oncogene expression correlated with the level of dysplasia of cervical lesions. HPV infection resulted in genetic instability may be one reason for the high incidence and mortality in Longnan.
Keywords: human papillomaviruses, E6/E7 oncogenes, DNA damage response, cervical cancer
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