HPV infection associated DNA damage correlated with cervical precancerous lesions and cancer in the highest area of cervical cancer mortality, Longnan, China

• Main Authors: Zhao J, Guo Z, Wang Q, Si T, Pei S, Qu H, Shang L, Yang Y, Wang L
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-07-01
• Series: Cancer Management and Research
• Subjects: Human papillomaviruses; E6/E7 oncogenes; DNA damage response; cervical cancer
• Online Access: https://www.dovepress.com/hpv-infection-associated-dna-damage-correlated-with-cervical-precancer-peer-reviewed-article-CMAR

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 Wang11Department 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 workObjectives: 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