Human papillomaviruses (HPV)

Papillomaviruses are a family of closely related agents that infect epithelial cells either of the skin or of inner 'mucosal' surfaces.

The virus matches its own life cycle to the life cycle of the epithelial cells and replicates to produce new virus particles just as the cells become 'squamous' and reach the surface of the skin or mucosa. This replication causes warts (papillomas).

Most warts are benign lesions which eventually clear up, for instance common skin warts caused by HPV types 1 and 2 or genital warts caused by HPV 6 and 11. However, other genital lesions can be caused by particular 'high risk' virus types such as HPV 16 and 18.

A small proportion of these can progress to malignant carcinomas, cervical cancer in women being by far the commonest example, but also including many penile,1 anal,2 vaginal,7 and vulval cancers.8  HPV infection is also linked to laryngeal and oral and pharyngeal cancers, with the strongest association found for oropharyngeal cancer.9-11,20 A study published in December 2011 estimated that around 5,100 cases of cancer in the UK in 2010 were linked to HPV infection.20

A key step in the malignant progression of HPV infection seems to be the accidental integration of viral DNA sequences into the genome of cells in the 'basal' epithelial layer, the cells in which papillomaviruses normally persist as a latent infection.

When the cells move upwards, replication to new virus particles no longer occurs and the normal progress of infection is interrupted. In some cases the integrated viral DNA retains the capacity to express particular early genes (E6 and E7). These become switched on permanently, they continue to produce viral proteins which can drive cell growth (see Figure 3.1 (a)).

Download this image (24KB)

Secondary genetic changes occurring in these latently-infected proliferating cells can then complete the oncogenic process ( Figure 3.2)3

Download this image (26KB)

The molecular evidence now strongly implicates Human Papilloma Virus (HPV) 16/18 and a few other closely related 'high risk' types as causative agents for cervical carcinoma.

Using modern assays, HPV DNA is found in almost 100% of cervical cancer and stage 3  cervical intraepithelial neoplasia (CIN3) samples world-wide4

The viruses are sexually transmitted and widespread in human populations; prevalence genital HPV infections in sexually active young women is as high as 40%5,6

Co-factors influencing the chances of progression of HPV infection in cervical cancer include cigarette smoking, higher parity, earlier age at first intercourse and immune suppression.12,13 Smoking also appears to interact with HPV in vulval cancer.14 Infection with certain other sexually transmitted infections may also act as a co-factor with HPV infection: A pooled analysis of case-control studies reported almost a doubling in risk of squamous cell carcinoma (SCC) of the cervix among women with evidence of infection with herpes simplex virus-2 (HSV-2) and with HPV DNA in cells compared with women positive for HPV only.15 HSV-2 infection has also been associated with an increased risk of anal cancer,16 vaginal cancer,17 in situ vulval cancer,14 and penile cancer.18 An international multi-centre case-control study reported a 70% risk increase for cervical SCC in HPV-positive women with antibodies to chlamydia trachomatis.19 In addition to HPV prevalence, these factors influence incidence rates of cervical cancer seen in different countries ( Figure 3.3) as does the existence of cervical screening programmes.

Download this map (27KB)

section reviewed 01/03/06
section updated 01/01/12