Human papilloma virus: Apprehending the link with carcinogenesis and unveiling new research avenues (Review)

Abstract

Human papilloma viruses (HPV) are a small group of non‑enveloped viruses belonging to the Papillomaviridae family with strong similarities to polyoma viruses. The viral particles consist of a genome in the form of a circular double‑stranded DNA, encompassing eight open reading frames, as well as a non‑enveloped icosahedral capsid. HPV infection is considered the most common sexually transmitted disease in both sexes and is strongly implicated in the pathogenesis of different types of cancer. 'High‑risk' mucosal HPV types, predominantly types 16, 18, 31, 33 and 35, are associated with most cervical, penile, vulvar, vaginal, anal, oropharyngeal cancers and pre‑cancers. Screening for HPV is necessary for the prognosis and for determining treatment strategies for cancer. Novel HPV markers, including proteomic and genomic markers, as well as anti‑papillomavirus vaccines are currently available. The aim of this comprehensive review was to thoroughly present the updated information on virus development, cancer occurrence, treatment and prevention strategies, in an attempt to shed further light into the field, including novel research avenues.

Figure 1

An HPV-infected cell is subjected to multiple transformations. HPV infects initially actively dividing basal epithelial cells. HPV then integrates into the host genome inducing specific alterations of host cellular gene expression. The expression of high-risk HPV E6/E7 proteins augments genomic instability and induces epigenetic and further transcriptomic alterations that generate proteins (proteome) that maintain a host cellular milieu favorable to viral genome replication. The altered infected cell develops modified intracellular events that induce aberrant proliferation and further generate immune response activation. On all altered levels, beginning from HPV insertion into the host cell genome, through epigenetic alteration and the transcription of altered proteins, biomarkers indicative of HPV infection can be identified. HPV, human papilloma virus.

Figure 2

The mechanisms of action of HPV vaccines. HPV, human papilloma virus; mRNA, messenger ribonucleic acid; tRNA, transfer ribonucleic acid; rRNA, ribosomal ribonucleic acid.