Papillomaviruses are a large family of small deoxyribonucleic acid (DNA) tumour viruses that cause hyperproliferative warts of cutaneous and mucosal epithelium. These viruses are ubiquitous in the animal kingdom and infect reptiles, birds and mammals and probably originated 350 million years ago. Subsets of human papillomaviruses (HPVs), referred to as ‘high‐risk’ types are associated with anogenital cancers (uterine cervix, vulva, vagina, anus, penis), oropharyngeal cancers and skin cancers. The papillomavirus life cycle is strictly dependent on the terminal differentiation programme of the host cell – the keratinocyte. The virus deregulates host cell cycle control and inactivates the host cells' antiproliferative response in order to reprogramme the differentiating cells to support viral replication. In the case of high‐risk viruses, this is achieved by interactions with important tumour repressor pathways. Two prophylactic vaccines (Gardasil and Cervarix) are available to control infection by the most prevalent HPV types found in anogenital and oropharyngeal cancers.
Key Concepts
Papillomaviruses show strong species and tissue restriction and they share a similar genetic organisation.
Papillomaviruses are small double‐stranded (ds) DNA viruses that replicate as non‐integrated episomes in keratinocytes and are dependent on the keratinocyte undergoing terminal differentiation in order to complete their life cycle.
Low‐risk viruses such as HPV6 and 11 are associated with the formation of anogenital warts and laryngeal papillomaviruses that have a low risk of progression to cancer.
The most severe impact of human papillomavirus infection is the progression of a small proportion of infections to anogenital, oropharyngeal and skin cancers.
High‐risk viruses such as HPV16 and 18 are associated with infections of the mucosa lining the anogenital and oropharyngeal tract and HPV16 is the most prevalent genotype in cancers arising at these sites.
A majority of HPV infections are naturally eliminated by host‐cell‐mediated immunity and HPV infections are especially common in immunocompromised individuals (e.g. HIV‐infected patients, organ‐recipient patients, predisposing genetic conditions, e.g. epidermodysplasia verruciformis).
These viruses are a common sexually transmitted disease (STD) and infection in the oropharynx is most likely via an oral‐genital route.
High‐risk HPV early proteins E5, E6 and E7 are oncoproteins and the expression of E6 and E7 is retained in all cancers; E6 and E7 deregulate tumour suppressor pathways leading to host genomic instability.
Papillomaviruses replicate as extrachromosomal plasmids in the nulei of infected cells, but during cancer progression, the viral genome often becomes integrated into the host chromosome, resulting in a loss of the negative feedback control of viral oncogene expression by E2.
Prophylactic vaccines protect against infection with vaccine‐associated HPV types by inducing neutralising antibodies that recognise epitopes on the major capsid protein.