Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis

• Published in: Infectious Agents and Cancer
• Main Authors: Arash Letafati, Zahra Taghiabadi, Negar Zafarian, Roxana Tajdini, Mozhgan Mondeali, Amir Aboofazeli, Silvia Chichiarelli, Luciano Saso, Seyed Mohammad Jazayeri
• Format: Article
• Language: English
• Published: BMC 2024-07-01
• Subjects: Oxidative stress; HPV-mediated carcinogenesis; Smoking; Alcohol; Psychological stress
• Online Access: https://doi.org/10.1186/s13027-024-00581-8

Abstract The contribution of the human papillomavirus (HPV) to cancer is significant but not exclusive, as carcinogenesis involves complex mechanisms, notably oxidative stress. Oxidative stress and HPV can independently cause genome instability and DNA damage, contributing to tumorigenesis. Oxidative stress-induced DNA damage, especially double-strand breaks, aids in the integration of HPV into the host genome and promotes the overexpression of two viral proteins, E6 and E7. Lifestyle factors, including diet, smoking, alcohol, and psychological stress, along with genetic and epigenetic modifications, and viral oncoproteins may influence oxidative stress, impacting the progression of HPV-related cancers. This review highlights various mechanisms in oxidative-induced HPV-mediated carcinogenesis, including altered mitochondrial morphology and function leading to elevated ROS levels, modulation of antioxidant enzymes like Superoxide Dismutase (SOD), Glutathione (GSH), and Glutathione Peroxidase (GPx), induction of chronic inflammatory environments, and activation of specific cell signaling pathways like the Phosphoinositide 3-kinase, Protein kinase B, Mammalian target of rapamycin (PI3K/AKT/mTOR) and the Extracellular signal-regulated kinase (ERK) signaling pathway. The study highlights the significance of comprehending and controlling oxidative stress in preventing and treating cancer. We suggested that incorporating dietary antioxidants and targeting cancer cells through mechanisms involving ROS could be potential interventions to mitigate the impact of oxidative stress on HPV-related malignancies.