HPV

Question 1

Virus associated cancers

1. What % of cancers are associated with virus infections?
2. What are the most common virus-associated cancers in females?
3. What are the most common virus associated cancers in males?

Answer 1

1. 10-20
2. Cervical Cancers
3. Liver cancers (HBV, HCV)

Question 2

Name the Viruses Associated with Human Cancer:

1. Retroviridae
2. Papillomaviridae
3. Hepadnaviridae
4. Flaviviridae
5. Herpesviridae
6. What % of human cervical cancer is associated with papillomaviruses?

Answer 2

1. HTLV1
2. HPV
3. HBV
4. HCV
5. Kaposi’s sarcoma associated herpesvirus
   (EBV can also cause cancer)
6. 99%

Question 3

Virus associated cancers

1. How long do the viruses last/infect?
2. How do these cancers vary?
3. Is the virus enough to cause cancer?
4. What part of the virus is found in the tumor cells?
5. How do other viruses contribute to cancer formation?

Answer 3

1. persistently infecting, last many years
2. vary geographically and culturally
3. no; viruses far more common than the tumors they cause
4. genome
5. may cause immunosuppression –> cancer growth (HIV)

Question 4

HPV Structure

1. Envelope?
2. genome
3. What is the capsid made of? how does it arrange?

Answer 4

1. no
2. double strand DNA, circular
3. L proteins (L1 is predominant); self assembly into pentameric units

Question 5

HPV Genome

1. What is the promoter of the L gene products?
2. Where is the promoter for the E gene products?

Answer 5

1. L2 proximal promoter

2. promoter near LCR

Question 6

HPV in epithelium

1. What is made first? genome or capsule?
2. What occurs in the basal keratinocytes?
3. What occurs in the spinosum?
4. What occurs in the Granulosum?
5. What occurs in the Corneum?
6. How stable is HPV in the environment?

Answer 6

1. Genome
2. HPV infects cell; injects viral DNA
3. HPV genome replication
4. Virions mature
5. dead epithelial cells are loaded with virions, which are spread when they desquamate?
6. VERY stable; can survive in the environment

Question 7

HPV

1. Gross manifestation
2. Where could is be clinically significant?
3. Time course between inoculation and gross manifestation?
4. How long does it take to resolve? Why?
5. When does cell transformation occur?

Answer 7

1. usually a wart
2. if the wart is in an airway
3. months
4. years to never; HPV is in the skin, which immune cells have a hard time reaching
5. rarely, after infection of the basal cells

Question 8

HPV integration

1. What happens to viral production after HPV is integrated into host genome?
2. What gene is “broken”?
3. What 2 genes are intact?
4. What does not occur if the 2 genes in (3) are broken?

Answer 8

1. no more viral production
2. E2
3. E6 and E7
4. cancer does not develop if E6 and E7 are broken

Question 9

HPV Cancer

1. Where can it spread?
2. What do the cells look like?
3. When can it develop?
4. HPV transmission

Answer 9

1. local metastasis; can go to nearby lymph nodes, rarely spreads beyond pelvis
2. highly vacuolated; haloes around shrunken nuclei;
3. years after HPV infection
4. Sexually

Question 10

HPV Diagnosis

1. Does it grow in culture?
2. What does (1) mean?
3. How is it diagnosed/categoried?
4. What is looked for by (3)? why?
5. Is dysplasia required for the test in (3) to pick up HPV?

Answer 10

1. no
2. hard to categorize via serology
3. DNA; RNA in Situ Hybridization
4. E6 and E7; latently infected cells will make those transcripts
5. No

Question 11

HPV

1. What does cell sense when viral DNA replicates?
2. What happens?
3. What does virus need to do?
4. How does it do this?

Answer 11

1. senses damaged DNA,
2. cell increases p53 and Rb to stop the cell from dividing and cause cell death; cell is trying to prevent cancer
3. Needs to deplete p53 and Rb so that it can continue to replicate
4. produces E6 and E7

Question 12

1. How does E6 reduce the amount of p53?

2. What does E7 bind to?

Answer 12

1. E6 and an adapter protein ubiquinates p53 many times; this leads to degradation of p53 and continued replication of the cell
2. p105RB

Question 13

HPV Vaccine

1. What is it made of?
2. What does it contain?
3. How is it given?
4. What % of cervical cancer does it protect against?

Answer 13

1. Virus-like particles
2. four HPV VLPs (6, 11, 16, 18)
3. 3 injections
4. 70% of cervical cancer