Way back in 1907 it was first realized that human warts were transmitted by a virus, although it was not until 1933 that Richard Shope isolated the first papillomavirus from rabbits. In spite of this early start, human papillomaviruses (HPV) remained largely unstudied until the development of molecular virology in the 1970s. This was because there were no good experimental systems for working with human papillomaviruses, since they stubbornly refused to grow in cultured cells. Since we started using DNA as an experimental tool, we have much more knowledge about how these viruses work and what serious pathogens they are.
As viruses go, papillomaviruses are pretty small, only around 55 nanometers in diameter. The particles are simple icosahedral structures containing a short, circular, DNA genome of about 8 kbp in size. Individual papillomavirus isolates are highly species specific, only replicating in their own host species. They like to grow in squamous epithelial cells, found in the skin and other epithelia. The virus infects the basal cells of the dermal layer, and causes them to continue to divide, forming a wart (or papilloma) on the surface of the skin.
Warts may occur almost anywhere in or on the body. Genital warts (sometimes called condylomas) occur in the genital tract and are sexually transmitted. Superficial warts can be treated by topical application of caustic substances or by freezing them with liquid nitrogen, but surgical removal is more reliable, and is needed for internal warts e.g. laryngeal in the throat. Once you’ve got them, warts may persist for many years, but in some cases they disappear spontaneously due to a cytoxic T-cell response. This gives rise to folk tales about wart charmers who have supernatural powers allowing them to cure people of warts. There is a small risk that skin warts exposed to ultraviolet light may develop into invasive squamous cell carcinomas, but this is very rare.
The really bad news about human papillomaviruses is that they are associated with tumours, including >95% of all cervical cancers and probably about 20% of head and neck cancers. Cervical cancer is estimated to kill 275,000 women worldwide every year, including more than 1000 in the UK.
At least 60 different types of HPV have been identified using molecular techniques, but in the last few years, a small number of types have been found to be to be associated with certain tumours, in particular cervical carcinoma. Odd as it may sound, that might turn out to be good news. Because they are quite simple viruses, and because we know that the right kind of immune response can clear people of warts, pharmaceutical companies have been working on vaccines against human papillomaviruses for some time.
Gardasil is a new vaccine made by Merck and Sanofi Pasteur. In clinical trials involving more than 25,000 women, the vaccine was 100% effective in preventing cervical cancer, pre-cancerous lesions, and genital warts caused by human papillomaviruses type 6, 11, 16 and 18. This is an amazing finding, but is explained by the fact that HPV 16 and 18 are responsible for 70% of all cervical cancers, and types 6 and 11 cause about 90% of cases of genital warts. This vaccine was approved for use in the USA in August, and in the EU in September. Other vaccines are in development by other manufactures but have not been approved for general use yet. The question now is, what should we do with it?
These new vaccines have caused controversy over plans to give it to girls as young as nine, before they become sexually active, so protecting them against disease. But in might make more sense to vaccinate both boys and girls in order to reduce the rate of infection more quickly, and in the hope of eventually eradicating HPV. An editorial in the Lancet has called for compulsory vaccination for girls in all EU member states at the age of 11 or 12 (Should HPV vaccines be mandatory for all adolescents? The Lancet 2006 368: 1212). Pretty strong stuff, but ethically speaking, if a vaccine is available which will save over a thousand lives each year in the UK alone, shouldn’t we use it? Or do parents have a right to expose their children to the risk of dying of cancer? You can comment on this issue below.
- Wikipedia: Papillomaviruses
- BBC: Cervical and Uterine Cancers
- Gardasil Quadrivalent Human Papillomavirus Vaccine