HPV tumourigenesis

Question 1

What amount of the global cancer burden is due to infection?

Answer 1

20%

Question 2

Which hepatitis viruses cause cancer?

Answer 2

B and C

Question 3

What HPV viral protein inhibits Rb?

Answer 3

E7

Question 4

Which HPV viral protein inhibits p53?

Answer 4

E6

Question 5

What are the proteins on the outside of HPV and what is their role?

Answer 5

L1 and L2 - late proteins 1 and 2 which defines which type of HPV is present (16 or 18).

Question 6

Which strains of HPV cause verrucas?

Answer 6

HPV-1 and HPV-2

Question 7

which HPV strains cause recurrent respiratory papillomatosis?

Answer 7

HPV-6 and HPV-11

Question 8

Which HPV strains cause cervical/anal/oropharyngeal cancer?

Answer 8

HPV-16 and HPV-18

Question 9

What is the role of E1 and E2 proteins?

Answer 9

DNA replication

Question 10

What is the role of E4 and E5 proteins?

Answer 10

DNA amplification of the viral genome in the upper layers of the epithelium

Question 11

What is the role of E6 and E7 proteins?

Answer 11

Oncogenic in high risk HPV types

Question 12

What is the HPV life cycle leading to infection

Answer 12

Entry occurs following micro-injury. This allows infection of the basal cell layer. Productive infection occurs in this layer. As the basal cells differentiate and move towards the cell surface, other viral proteins begin to be expressed with the aim to produce more viral particles (E1, E2) then at the epithelial surface L1 and L2 which packages the virus and releases it, allowing for spread of infection.

Question 13

How does the HPV life cycle change in cancer?

Answer 13

Instead of the productive life cycle there is a latent infection. This is caused by high expression of E6 and E7 which causes episomal infection or integration. You get loss of p53 and RB which leads to epithelial proliferation.

Question 14

What break point in the HPV genome is commonly seen in cancer?

Answer 14

At E2. This prevents the expression of E2 which would normally downregulate E6/7 expression. If this integrates into host DNA then E6/E7 will be highly expressed which will be cancer inducing

Question 15

How does E6 lead to the loss of p53 function?

Answer 15

Associates with an E3 ubiquitin ligase which tags p53 for degradation

Question 16

How does E7 lead to the loss of RB

Answer 16

Associates with an ubiquitin ligase complex which tags RB1 for degradation - can no longer associate with E2F…

Question 17

What is CIN 1

Answer 17

Mild dysplasia

Question 18

What is CIN 2?

Answer 18

Moderate dysplasia

Question 19

What is CIN 3?

Answer 19

Severe dysplasia to carcinoma in situ

Question 20

Why are HPV positive tumours normally WT for TP53?

Answer 20

Tumour gains no benefit from mutations in p53 because E6 degradation of p53 is occurring

Question 21

What becomes overexpressed in HPV positive cancers? What is the result of this?

Answer 21

p16INK4A, results in low expression of cyclin-D.

Question 22

Why is there disruption of the HPV16 life cycle in HNSCC development?

Answer 22

For immune evasion

Question 23

How does HPV infection change when you are HIV positive.

Answer 23

Persist for longer. Makes more HPV strains (not just 16 and 18) to be able to cause cancer.