Human papillomavirus - cervical cancer
Hepatitis B and C - liver cancer
HIV and Kaposi's sarcoma
Oncogenesis is the accumulation of genetic changes that alter proteins that control cell growth and division. Oncogenic virsuses can affect these changes. Retroviruses insert DNA into our DNA which can alter human DNA to upregulate these things.
Human viruses:
HPV - cervical cancer
Herpes - Kaposi's sarcoma and Epstein-Barr Virus (after immunosuppression)
HBV and HCV - liver cancer
Most important ones:
Hepatitis C
Human T-cell leukaemia virus type 1
Human Papillomavirus
Epstein-Barr virus
Hepatitis B
Immune control is vital in cancer development, as usually the immune system controls elimination, equilibrium and finally evasion.
Koch's postulates:
- regular association
- virus can be taken from host and grown in culture
- reintroduced virus causes disease
- reintroduced virus can be extracted and grown in culture
This does not occur in all viruses that are involved in human cancer.
Obviously introducing vaccines has been shown to reduce the rate of cancer.
KSHV is an AIDs defining illness. There are different types of KS and it was first seen in elderly Mediterranean men and then it became noticeable in a number of young homosexual men. This was associated with HIV. It can also be caused in an iatrogenic way or endemically.
In HIV infection there is a 200,000 times higher incidence of KSHV than in the general population. There is a proved connection between KS and KSHV. In the spindle cells of KS there is Latent nuclear antigen (LANA). KS causes tumour products transcriptionally. In KSHV there are phenotypic changes from cobblestone to spindle cells.
Koch's postulates have been updated as they don't work exactly in relation to viruses associated with cancer. The viruses are obviously related and the tumours show copies of the KSHV, however, it can't be isolated and reintroduced- ethically this is not viable! In macaque monkeys this has been shown to increase the chance of tumour.
Zur Hausen updated the criteria:
-regular presence and persistance in biopsies
-growth promotion of upregulated genes
-malignant phenotype dependent on expression of the genes
-major risk factor for the development of tumour
Eukaryotic cell cycle is a very ordered process which means all the right factors need to come together to downregulate inhibition and increase the proliferation. The signals are produced in the cell and it regulates itself. The processes are M, G1, S and G2. Cytokines regulate the whole process, which cyclins. CDKs are involved. Usually the inhibitors of the cyclins and cytokines prevent proliferation.
HPV affects the non-differentiating keratinocytes to replicate in an unregulated manner. In the upregulation, the host usually acts to prevent proliferation by trying to apoptose cells usually but HPV suppressing the RB gene and phosphorylating this protein and suppressing p53. HPV E6 binds to p53 causes lack of transcription of cell cycle inhibitors. We can vaccinate against this by giving empty capsids, meaning you get the immune response to the virus stopping you from getting it.
Newcastle disease from chickens can cause an 'immunity' to stomach cancer!
Retroviruses cause the responses. However, there can be latency as the virus needs to insert near the gene it wants to activate to cause the change in the cell cycle. For example, if the virus is near c-myc gene this upregulates the gene. It is hard to attribute the cause to a virus.
Tumour associated viruses show us a lot about which genes are essential in cancer.
Novel therapeutic approaches involve vaccines.