Genital HPV is a common sexually transmitted disease that is responsible for over 50 000 new cases of cancer per year. The genetics of papilloma virus and its tumorigenic effects are now well understood. This information could generate new ways to prevent and treat HPV related malignancy.
Human Papilloma Virus (HPV) Facts
- HPV is a transforming retrovirus. It is able to circumvent the effects of tumor suppressor genes and initiate malignant change within infected cells.
- HPV infection can cause cancer of the cervix, anus, vulva and penis, as well as cancers of the head and neck.
- More than 130 types of HPV have been identified and are classified as low or high risk, according to their ability to cause cervical cancer upon persistent infection.
- Approximately 70% of cervical cancers are associated with HPV types 16 and 18.
- In around 90% of people HPV infection is asymptomatic and is cleared within 2 years.
- It is hoped that the recent development of HPV vaccines will reduce the incidence of cervical cancer and limit the spread of HPV-associated oral cancer.
The Genetics of Papilloma Virus and its Oncogenic Potential
The genetics of papilloma virus and the pathogenesis of HPV associated malignancy is better understood than many other viral induced cancers. This is partly because cervical cancer screening programmes have aided long-term study of the HPV disease process.
Malignancy may take up to 15 years to develop. HPV associated carcinogenesis involves chronic inflammation and complex interactions with the infected individuals immune system. For carcinogenesis to occur, the viral DNA must integrate into the host genome. Expression of two viral genes called E6 and E7 are fundamental to the process, as well as a sequence of epigenetic effects.
The tumor suppressor gene p53 is the most frequently mutated gene in human cancer and is estimated to be altered in around 50% of malignancies. The E6 oncogene product from HPV associates with a cellular protein called E6-associated protein (E6-AP). E6 and E6-AP induce the rapid degradation of p53, therefore removing the tumor suppressive effects.
Another oncogenic factor in infected cells is the HPV oncogene E7. This inhibits the function of the retinoblastoma protein (Rb). Inappropriate inactivation of Rb usually triggers a strong antiproliferative response by the p53 protein in order to protect against cancerous change. However HPV is able to inactivate both p53 and Rb and hence can induce malignancy when accompanied by certain environmental and host related factors.
Cervical Cancer Screening
National cervical screening programs in Europe and the US have had a positive impact on the death rate from cervical cancer. However in developing countries, scarce resources and a lack of infrastructure have been barriers to effective mass screening programmes. As a result, 83% of cervical cancers occur in developing nations.
The introduction of a prophylactic HPV vaccine could have a major impact on reducing this disease globally. However, long-term surveillance of the HPV vaccination program will be needed to see if it does indeed produce the desired results.
References
Human tumor-associated viruses and new insights into the molecular mechanisms of cancer. D.Martin and J.Gutkind. Oncogene (2009) 27, S31–S42
Prophylactic HPV vaccination: a major breakthrough in the fight against cervical cancer? A.Saleem, A.Tristram, A.Fiander, S.Hibbetts. Minerva Med. 2009, Vol 100, P503-23
