Human papilloma virus (HPV) mediated cancers: an insightful update

Abstract

Human papillomavirus (HPV), a DNA virus, is a well-documented causative agent of several cancers, including cervical, vulvar, vaginal, penile, anal, and head & neck cancers. Major factors contributing to HPV-related cancers include persistent infection and the oncogenic potential of particular HPV genotypes. High-risk HPV strains, particularly HPV-16 and HPV-18, are responsible for over 70% of cervical cancer cases worldwide, as well as a significant proportion of other genital and head and neck cancers. At the molecular level, the oncogenic activity of these viruses is driven by the overexpression of E6 and E7 oncoproteins. These oncoproteins dysregulate the cell cycle, inhibit apoptosis, and promote the accumulation of DNA damage, ultimately transforming normal cells into cancerous ones. This review aims to provide a comprehensive overview of the recent advances in HPV-related cancer biology and epidemiology. The review highlights the molecular pathways of HPV-driven carcinogenesis, focusing on the role of viral oncoproteins in altering host cell targets and disrupting cellular signalling pathways. The review explores the therapeutic potential of these viral proteins, and discusses current diagnostic and treatment strategies for HPV-associated cancers. Furthermore, the review highlights the critical role of HPV in the development of various malignancies, emphasizing the persistent challenges in combating these cancers despite advancements in vaccination and therapeutic strategies. We also emphasize recent breakthroughs in utilizing biomarkers to monitor cancer therapy responses, such as mRNAs, miRNAs, lncRNAs, proteins, and genetic markers. We hope this review will serve as a valuable resource for researchers working on HPV, providing insights that can guide future investigations into this complex virus, which continues to be a major contributor to global morbidity and mortality.

Keywords: Apoptosis; Cancer; Cell cycle; E6; E7; HPV; Oncoproteins; Therapeutics.

Fig. 1

A HPV genome organization. The genome of HPVs, about ∼7.9 kb circular double-stranded DNA, consists of approximately eight open reading frames (ORFs), which can be functionally categorized into three main regions: the E region, the L region, and the long control region (LCR). Early and late promoters (p) are denoted p97 and p670, respectively; early and late polyadenylation sites are denoted pAE and pALs, respectively with straight lines above the circular genome. B The HPV infection starts in the basal epithelial cells upon injury/trauma/permeability and ends with the assembly and virion release at the very top terminally differentiated epithelial cells. Early genes of E1, E2, E6, E7, E4, E5 and late genes of L1 and L2 are expressed in basal to superficial layers during the infection initiation, progression, and termination. Complete virions are then shed from the surface of the squamous epithelium in a non-lytic manner

Fig. 2

Integration of the HPV genome into the host genome induces disruption of the E2 gene, leading to the consecutive expression of the oncogenes E6 and E7, resulting in induced cellular immortalization, transformation, and, ultimately, carcinoma

Fig. 3

Events mediated and modulated by HPV E6/E7

Fig. 4

Tumor-associated signalling pathways regulated by HPV E6/E7

Fig. 5

Depiction of HPV-related cancers comparing percentages of HPV-associated and other causes