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
A key step in this progression 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)).
Secondary genetic changes occurring in these latently-infected proliferating cells can then complete the oncogenic process (Figure 3.2)3.
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-wide 4.
The viruses are sexually transmitted and widespread in human populations; prevalence genital HPV infections in sexually active young women is as high as 40%56.
Co-factors influencing the chances of progression include cigarette smoking, higher parity, earlier age at first intercourse, infection with other sexually transmitted infections and immune suppression. These influence incidence rates of cervical cancer seen in different countries (Figure 3.3) as does the existence of cervical screening programmes.
References for Human papillomaviruses (HPV) and cancer
- Daling JR, Madeleine MM, Johnson LG, et al.Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. IJC 2005;116(4):606-16.
- Daling JR, Madeleine MM, Johnson LG, et al.Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer 2004;101(2):270-80.
- Fehrmann, L. and L. Laimins, .Human papilliomaviruses: targetting differentiating epithelial cells for malignant transformation. Oncogene, 2003. 22(33): p. 5201-5207
- Walboomers, J., M. Jacobs, and M. Manos, Human Papillomavirus is a necessary cause of invasive Cervical Cancer Worldwide. Journal of Pathology, 1999. 189: p. 12-19
- Baseman, J. and L. Koutsky, .The epidemiology of human papillomavirus infections. J Clin Virol, 2005. 32S: p. S16-S24
- Clifford, G.M., et al., .Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet, 2005. 366(9490): p. 991-8
- Daling JR, Madeleine MM, Schwartz SM, et al. .A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 2002;84(2):263-70
- Carter JJ, Madeleine MM, Shera K, et al. .Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites Cancer Res 2001;61(5):1934-40.
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