HPV Infection and Oxidative Stress in Cervical Carcinogenesis: Linking Apoptosis, Senescence, SASP, and EMT

Despot, Albert; Fureš, Rajko; Despot, Ana-Marija; Hrgović, Zlatko; Gredičak, Martin; Malinac Malojčić, Sanja; Ćosić, Vesna; Mešić, Larisa; Sinković, Nikola; Sabol, Ivan (2026) HPV Infection and Oxidative Stress in Cervical Carcinogenesis: Linking Apoptosis, Senescence, SASP, and EMT. Antioxidants, 15 (4). ISSN 2076-3921

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Abstract

Cervical cancer (CC) is a complex, multistep process involving various viral, molecular, cellular, endogenous, and environmental events that transform normal cervical epithelium into a malignant tumor through a cascade of events. The contribution of high-risk human papillomavirus (HPV) to cancer is significant but involves many additional mechanisms such as oxidative stress (OS), arrested apoptosis of non-functional intraepithelial neoplastic cells, senescence-associated secretory phenotype (SASP), and the final epithelial–mesenchymal transition (EMT) of cervical epithelial neoplasia (CIN) cells. While high-risk HPV oncoproteins E6 and E7 are widely recognized as the primary triggers of CC, the critical role of E6 in degrading the p53 regulatory protein, thereby inhibiting the apoptosis of reactive oxygen species (ROS)-damaged neoplastic cells, is frequently underappreciated in the gynecological literature. Arrested apoptosis of non-functional neoplastic intraepithelial cells is a key event in cervical carcinogenesis and the biological basis of CIN progression via SASP senescence and ultimately EMT. While recent reviews touched upon each of the reviewed aspects, this review aims to provide a general understanding of all links in this complex molecular-biological chain, from HPV infection, oxidative stress, arrested apoptosis, SASP, and EMT. Beyond providing an encompassing primer for clinical researchers, we additionally review potential oxidative stress-related markers for shifting the classic diagnostic and therapeutic paradigms of CIN and cervical cancer.

Item Type:	Article
Uncontrolled Keywords:	ROS; SASP; HPV; cervical cancer
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions:	Division of Molecular Medicine
Depositing User:	Ivan Sabol
Date Deposited:	21 Apr 2026 05:38
URI:	https://fulir.irb.hr/id/eprint/11735
DOI:	10.3390/antiox15040486

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