Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection

• Published in: Journal of medical virology 2016-02, Vol.88 (2), p.336-344
• Main Authors: Visalli, Giuseppa, Riso, Romana, Facciolà, Alessio, Mondello, Placido, Caruso, Carmela, Picerno, Isa, Di Pietro, Angela, Spataro, Pasquale, Bertuccio, Maria Paola
• Format: Article
• Language: English
• Subjects: 8-Oxo-2′-deoxyguanosine; Adolescent; Adult; Biomarkers - analysis; cervical lesions; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - analysis; DNA Damage; Female; high-risk HPV; Human papillomavirus; Humans; Middle Aged; Mutagens - toxicity; Oncogene Proteins, Viral - biosynthesis; Oncogene Proteins, Viral - genetics; Oxidative stress; Papillomavirus Infections - complications; Papillomavirus Infections - pathology; Reactive Oxygen Species - toxicity; RNA, Messenger - analysis; RNA, Messenger - genetics; Uterine Cervical Dysplasia - pathology; Virology; Young Adult
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.24327

The Human papillomavirus is responsible for the most common sexually transmitted infection and is also known to be an oncogenic virus that is associated with cervical, anogenital, and head‐neck cancers. The present study aims to assess whether oxidative DNA damage is correlated with the grade of HPV‐related lesions. Moreover, we evaluated clinical data and unhealthy lifestyles to verify their possible influence on the genesis of oxidative DNA damage in cervical cells. We quantified the amount of 8‐Oxo‐2′‐deoxyguanosine in DNA as a biomarker of oxidative damage in women with and without HPV infection. We also correlated oxidative damage with different stages of cervical lesions and available clinical data (e.g., HPV genotypes). To identify HPV infections, in which proteins with a transforming potential are produced, we performed a qualitative detection of HPV E6/E7 mRNA. Our results showed greater oxidative damage in HPV‐related dysplastic cervical lesions compared to samples with normal cytology, especially in women with high‐grade squamous intraepithelial lesions. The latter showed a closed link with high‐risk HPV genotypes. Reactive oxygen species can induce DNA double‐strand breaks in both the host DNA and in the circular viral episome; this could facilitate the integration of the virus, promoting HPV carcinogenesis. Therefore, in HPV‐infected women, it could be useful to reduce additional resources of reactive oxygen/nitrogen species (RONS) with a healthy lifestyle. J. Med. Virol. 88:336–344, 2016. © 2015 Wiley Periodicals, Inc.