Viruses and cancer Flashcards
List some type 1 carcinogen infections.
Viruses:
EBV, Hep B/C, HIV, HPV, Kaposi sarcoma herpes, human T-cell lymphotropic
Bacteria:
Helicobacter Pylori
Liver flukes/worms:
Schistosoma haematobrim, clonorchis sinensis
In which countries is the incidence of carcinogenic viruses higher?
Less developed countries
What cancers are caused by HIV-1?
Hodgkin’s and Non-Hodgkin’s lymphoma, cervial, anal and conjunctiva.
What is the risk to patients infected with HIV with regards to cancer?
The incidence of cancers caused by other infectious agents increases due to immunodeficiency. = indirect carcinogen
Why is causality in viruses difficult to establish?
Have long latency period
Only a small portion of those infected will develop cancer
Is a multi-step pathogenesis
Viruses is only a contributing factor, cannot cause cancer alone
No experimental animal models for human cancer
Give an example of a cancer caused by a virus that shows the development of cancer is multifactorial.
EBV is a common persistent infection that asymptomatically infects 95% of the world in childhood, with a lifelong latency. Only a small proportion of these will go on to develop epithelial cancers e.g. nasopharyngeal on the consumption of nitrosamines in salted fish
or
Burkitt’s lymphoma from myc translocation.
Which virus was found to be linked to Kaposi sarcoma?
HHV8 / KSHV - found in tumours but not in normal tissue. Affects HIV +ve pts more and is more common in homosexual men and women who have bisexual partners. Unknown if virus is the cause. Sexually transmitted infection.
Which virus is linked to aggressive Merkel cell carcinoma?
Merkel Cell Polyomavirus - Causes neuroectodermal tumour of Merkel cells in the skin. It is very aggressive and most evident in IMMUNOSUPPRESSED pts. MCPV is a common skin infection but only a few develop cancer. The structure of the virus in the tumour is different to that of the skin.
What is believed to be the cause for rising incidence in childhood leukaemia?
Has been linked to a virus, particularly near nuclear plants but not due to the radiation but due to the continuous flow of new workers that will bring new strains into the area.
How does HPV cause cancer?
A direct carcinogen via E6 and E7 viral proteins, particularly in immunosuppressed. It infects mitotically active basal cells to replicate without integrating into host when they’re inactive. Uses proliferation to amplify its genome and assemble new viruses. It is released through epithelial shedding. It causes host cells to replicate and promotes survival.
How does E6 impact a cell?
Deregulates p53 by removing it with proteosomes.
How does E7 impact a cell?
Stimulates cell proliferation by deregulating pRb.
Where does HPV target?
Targets stratified epithelium by utilising its differentiation and replication factors.
What cancers are caused by HPV?
Skin, head and neck, tonsils and tongue, cervical, external genitalia, anal.
What is the function of Rb?
Regulates progress from G1 to S phase.
What happens if Rb is deregulated by E7?
Continuous movement into S phase even if there is DNA damage present, increasing mutation levels.
How does a cell normally compensate for the loss of Rb?
It will increase p53 for apoptosis to prevent further replication of the virus within the cell.
How does the virus overcome the increased levels of p53?
E6 deregulates p53 = cell survival. This reprogrammes the cell with E6 and E7 working cooperatively.
What does the loss of the two tumour suppressor pathways result in?
Deregulating Rb and p53, promotes genome instability and increases the risk of acquiring an oncogenic mutation. q
What has been done to reduce the incidence of cancer development from oncogenic viruses?
Hep B vaccine
Cervical screening programme
HPV vaccine
What cancer has Hep B vaccine helped to reduce the most?
Liver cancer, by introducing viral surface antigens to the immune system. Used in newborns.
Who is eligible for cervical screening and what is its purpose?
For >25 year olds every 3 years and 50-64 every 5 years. It monitors cytological abnormalities in the cervix by looking for large nuclei and small cytoplasm. The woman is on a database so is continuously recalled until attends. Incidence is falling and coverage is increasing, but expensive so not used in countries with low incidence.
What is the HPV vaccine?
Contains virus like particles made up of the capsid protein L1. It introduces neutralising antibodies into the system. It is used prophylactically.
What are the two most common types of HPV? What is the vaccine for these?
HPV16 and HPV18. Cervarix
How effective is the HPV vaccine?
In naive pts who have never been infected = 100%
In pts previously infected = 50%
Shows the vaccine needs to be given prior to sexual activity and therefore prior to infection.
Why will it take time for the full impact of the vaccine to be experienced?
The vaccine is currently used in young girls, so as the vaccinated women get older and more young girls get vaccinated the incidence will fall.
Why are cervical smears still needed despite the HPV vaccine?
It only protects against some strains of HPV.
What are the 4 characteristics of oncogenic viruses?
- Common persistent infection with long latency
- Higher incidence of cancer development in immunosuppressed pts
- Complex multistep process that involves cofactors for cancer development. e.g. smoking and HPV, salted fish and EBV
- The infection is only part of the development and so the viral genes can be targeted by prophylactic vaccines
