Shadi Setayeshi,1,*
1. Department of Medical Biotechnology, Faculty of Medicine, Babol University of Medical Sciences
Introduction: Human papillomaviruses (HPVs) are minute viruses that carry deoxyribonucleic acid (DNA) and are part of the Papillomaviridae family. More than 200 types of HPV have been established and classified into 29 genera, and most of them impact humans. HPVs linked with cancers of the uterine cervix, anogenital tumors, and head and neck malignancies. Oxidative stress (OS) represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. Worldwide, cervical cancer is the second most common malignancy in women, impacting about 35 of every 100,000 women. Attention given to the link between HPV and cancer was significantly raised when HPV types 16 and 18 were detected in cervical cancers and preneoplastic dysplasia, the lesions that can make a woman susceptible to malignancy of the uterine cervix. The aim of this study was to review available evidence evaluating the role of oxidative stress in Human papillomaviruses pathogenesis and cervical cancer.
Methods: An electronic search with time (recent ten years, up to 2021) and language (English) restrictions was conducted using PubMed in order to find relevant studies to the research question. The search terms included “Human Papillomavirus”, “HR-HPV”, “Reactive oxygen species (ROS)”, “Oxidative marker”, “Oxidative stress (OS)”, “cervical cancer “, were used individually or/and in various combinations to retrieve the relevant kinds of literature. Most recent studies including case-control studies, original research, and review articles were selected.
Results: For investigation of the oxidative stress role in the pathogenesis of diseases, mainly, studies have examined oxidative stress biomarkers in cervical tissue and modulation of proteins involved in the redox status regulation. In vivo study by redox proteomic approach showed five proteins which have been found to have increased levels of carbonyls in dysplastic samples (HPV-16 positive tissues) namely: cytokeratin 6, actin, cornulin, retinal dehydrogenase and GAPDH. One recent study looked at the role of the early expressed viral proteins E1, E2, E6, and E7 from HPV types 16 and 18 in the modulation of the redox state reported that the combined expression of E1 and E2 proteins increased ROS levels with the subsequent increase in the marker for DNA damage.
Conclusion: The upregulation of stress protein markers indicated that an increased oxidative environment occurs both in dysplastic and neoplastic tissues. However, in dysplastic tissues this condition resulted in oxidative modification of DNA and of proteins involved in cell morphogenesis and terminal differentiation such as CK6, actin, cornulin, RDH and GAPDH, providing the conditions for the neoplastic progression. Further studies are needed to better understand the effects of protein oxidation on cell transformation and cancer promotion.
Keywords: Human papillomaviruses, Oxidative stress, Reactive oxygen and nitrogen species, Antioxidant.