Lipid metabolism and oxidative stress in HPV-related cancers

Abstract

High-risk human papillomavirus (HR-HPVs) are associated with the development of cervical, anus, vagina, vulva, penis, and oropharynx cancer. HR-HPVs target and modify the function of different cell biomolecules such as glucose, amino acids, lipids, among others. The latter induce cell proliferation, cell death evasion, and genomic instability resulting in cell transformation. Moreover, lipids are essential biomolecules in HR-HPVs infection and cell vesicular trafficking. They are also critical in producing cellular energy, the epithelial-mesenchymal transition (EMT) process, and therapy resistance of HPV-related cancers. HPV proteins induce oxidative stress (OS), which in turn promotes lipid peroxidation and cell damage, resulting in cell death such as apoptosis, autophagy, and ferroptosis. HR-HPV-related cancer cells cope with OS and lipid peroxidation, preventing cell death; however, these cells are sensitized by OS, which could be used as a target for redox therapies to induce their elimination. This review focuses on the role of lipids in HR-HPV infection and HPV-related cancer development, maintenance, resistance to therapy, and the possible treatments associated with lipids. Furthermore, we emphasize the significant role of OS in lipid peroxidation to induce cell death through apoptosis, autophagy, and ferroptosis to eliminate HPV-related cancers.

Keywords: Apoptosis; Cellular trafficking; Epithelial-mesenchymal transition (EMT); Ferroptosis autophagy; Lipid metabolism; Lipogenesis; Reactive oxygen species (ROS); β-oxidation.