Viruses and cancer

Question 1

List some type 1 carcinogen infections.

Answer 1

Viruses:
EBV, Hep B/C, HIV, HPV, Kaposi sarcoma herpes, human T-cell lymphotropic
Bacteria:
Helicobacter Pylori
Liver flukes/worms:
Schistosoma haematobrim, clonorchis sinensis

Question 2

In which countries is the incidence of carcinogenic viruses higher?

Answer 2

Less developed countries

Question 3

What cancers are caused by HIV-1?

Answer 3

Hodgkin’s and Non-Hodgkin’s lymphoma, cervial, anal and conjunctiva.

Question 4

What is the risk to patients infected with HIV with regards to cancer?

Answer 4

The incidence of cancers caused by other infectious agents increases due to immunodeficiency. = indirect carcinogen

Question 5

Why is causality in viruses difficult to establish?

Answer 5

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

Question 6

Give an example of a cancer caused by a virus that shows the development of cancer is multifactorial.

Answer 6

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.

Question 7

Which virus was found to be linked to Kaposi sarcoma?

Answer 7

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.

Question 8

Which virus is linked to aggressive Merkel cell carcinoma?

Answer 8

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.

Question 9

What is believed to be the cause for rising incidence in childhood leukaemia?

Answer 9

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.

Question 10

How does HPV cause cancer?

Answer 10

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.

Question 11

How does E6 impact a cell?

Answer 11

Deregulates p53 by removing it with proteosomes.

Question 12

How does E7 impact a cell?

Answer 12

Stimulates cell proliferation by deregulating pRb.

Question 13

Where does HPV target?

Answer 13

Targets stratified epithelium by utilising its differentiation and replication factors.

Question 14

What cancers are caused by HPV?

Answer 14

Skin, head and neck, tonsils and tongue, cervical, external genitalia, anal.

Question 15

What is the function of Rb?

Answer 15

Regulates progress from G1 to S phase.

Question 16

What happens if Rb is deregulated by E7?

Answer 16

Continuous movement into S phase even if there is DNA damage present, increasing mutation levels.

Question 17

How does a cell normally compensate for the loss of Rb?

Answer 17

It will increase p53 for apoptosis to prevent further replication of the virus within the cell.

Question 18

How does the virus overcome the increased levels of p53?

Answer 18

E6 deregulates p53 = cell survival. This reprogrammes the cell with E6 and E7 working cooperatively.

Question 19

What does the loss of the two tumour suppressor pathways result in?

Answer 19

Deregulating Rb and p53, promotes genome instability and increases the risk of acquiring an oncogenic mutation. q

Question 20

What has been done to reduce the incidence of cancer development from oncogenic viruses?

Answer 20

Hep B vaccine
Cervical screening programme
HPV vaccine

Question 21

What cancer has Hep B vaccine helped to reduce the most?

Answer 21

Liver cancer, by introducing viral surface antigens to the immune system. Used in newborns.

Question 22

Who is eligible for cervical screening and what is its purpose?

Answer 22

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.

Question 23

What is the HPV vaccine?

Answer 23

Contains virus like particles made up of the capsid protein L1. It introduces neutralising antibodies into the system. It is used prophylactically.

Question 24

What are the two most common types of HPV? What is the vaccine for these?

Answer 24

HPV16 and HPV18. Cervarix

Question 25

How effective is the HPV vaccine?

Answer 25

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.

Question 26

Why will it take time for the full impact of the vaccine to be experienced?

Answer 26

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.

Question 27

Why are cervical smears still needed despite the HPV vaccine?

Answer 27

It only protects against some strains of HPV.

Question 28

What are the 4 characteristics of oncogenic viruses?

Answer 28

• 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