HEPATITIS B AND CANCER
In the case of liver cancer, we also have detailed knowledge of the most frequent carcinogen – hepatitis B infection. The disease is a massive cause of suffering worldwide, but particularly in China and other parts of Asia where up to 10% of the population is chronically infected. There are lower rates in India and the Middle East, with rates less than 1% in Europe and North America. The risk of developing chronic infection is highest in those infected in infancy. Since 1982, a vaccine to HBV has been available. With vaccine programmes in place in various countries for some years, this has allowed scientists to complete the final test of the link between a virus and cancer – if the link were causal, preventing infection should and did prevent the disease. The precise molecular mechanism whereby the virus causes cancer is still being studied, but, as with smoking, the evidence for causation is now compelling.
Moving on to another cancer linked to infection – cervical cancer – we can see a similar story emerging. It was observed in the 1920s that cervical cancer was more common in women who had had high numbers of sexual partners, in particular prostitutes, and it was rare in nuns (except for those who had been previously sexually active), suggesting an infective, sexually transmitted cause. The disease was shown to be linked to infection with the human papillomavirus (HPV) by Harald Zur Hausen in 1976. Dr Zur Hausen found HPV DNA in both genital warts and cervical cancer. He received the Nobel Prize for Medicine for this discovery and his subsequent work in the field, which demonstrated the precise molecular links between the virus and the cancer. The virus produces various proteins which interact with two genes called Rb and p53, both key controllers of the cell cycle, providing an obvious route for generating cancer.
The development of a vaccine against HPV and hence cervical cancer has proved more technically challenging than the HBV vaccine. However, the linkage between chronic viral infection and cancer allowed the study of the pre-malignant stages of cervical cancer. This led to the discovery that these could be identified in smears of cells taken with a wooden spatula from the cervix and then examined under the microscope. Identification of the pre-cancer stage, called cervical intra-epithelial neoplasia (CIN) or carcinoma-in-situ (CIS), allowed preventative treatment. Most European and North American countries have comprehensive screening based on the cervical smear test. These programmes have been estimated to have saved many thousands of lives. More recently, a vaccine against the varieties of HPV linked to cervical cancer became available in 2006 and is beginning to appear in public health vaccine programmes for girls as a way of preventing infection, with consequent reduction in cancer risk. There is some controversy about the vaccine as some interpret it as a way of protecting against the risks of promiscuity. However, protection against one sexually transmitted disease does not lower risks from others such as HIV. In addition, the vaccine will protect women against the risks of prior promiscuity in their partners, something they have no control over whatsoever. It will, however, take 10 to 20 years for this benefit to be seen, as this is the typical time lag between HPV infection and the development of cancer.