HPV, warts, cervical cancer

Question 1

What % of cervical cancer and % of head and Neck cancers are due to HPV?

Answer 1

99% cervical cancers
- associated with high risk HPVS: 16, 18

25% H&N

Question 2

Is HPV a DNA or RNA virus?

Enveloped or non enveloped?

Answer 2

Non enveloped
DS DNA virus

*note: HPV causes >5% of all human cancers

Question 3

HPV capsid structure

Answer 3

consists of:

Capsid protein L1
(major)

Capsid protein L2
(minor)

• these spontaneously form pentamers that are targets for vaccine development

Question 4

Late Genes of HPV

Answer 4

Major capsid protein: L1

Minor capsid protein: L2

• structural

Question 5

Early genes of HPV: E5, 6,7 fxn

Answer 5

E5, E6, E7

All are Involved in:

1. Replication
2. Transcription
3. Transformation
4. Immune escape

E6 + E7: inhibit tumor suppressors p53 & Rb

Question 6

Early genes of HPV: E1, E2

Answer 6

E1: helicase, DNA rep

E2: transcription factor, viral genome maintenance

Question 7

HPV life cycle is linked to ________

Answer 7

stratified epithelial cell differentiation

• infects only undifferentiated proliferating basal layer cells
• being produced only from fully differentiated upper layer cells

Question 8

Nonsexual routes of HPV transmission

Answer 8

HPV:

Mother –> newborn

Fomites: undergarments, surgical gloves

*very stable

Question 9

Is persistence of high risk HPV types required for cancer development?

Answer 9

Yes

*persistent infxn: detection of same HPV type two/m times in 1 yr.

Question 10

# of HPV genotypes
List 2 high risk mucosal HPV genotypes and 
2 Low risk genotypes

Answer 10

180 genotypes
- vary in DNA seq by 20-30%

High risk: 16, 18
- what most vaccines are against

Low risk:
6, 11

Question 11

Where do cervical cancers target?

Answer 11

transformation zone
- area of immature metaplasia between original and current squamocolumnar jxn

*see slide

Question 12

Where do HPV H&N cancers target?

Answer 12

squamous cells of mouth/throat

*25% of H&N cancers are assoc w/ HPV infxn

Question 13

Cervical cancer progression

Answer 13

Normal –>
CIN1 –>
CIN2/3 –>
Cancer

or

Nl –>
LSIL –>
HSIL –>
Cancer

*CIN = cervical intraepithelial neoplasia

Question 14

> 80% of indiv will get HPV infection, how many will progress to CIN 2/3?

Answer 14

10% will through 7-15 yrs

Question 15

How to dz HPV

Answer 15

Pap smear/HPV test –>
HPV negative –>
Repeat HPV test in 3-5 years

Pap smear/HPV test –>
HPV positive –>
Cytology negative –>
repeat cytology & HPV test in 6-12 months

Cytology positive –> Colposcopy/histology

Question 16

Which is more effective? HPV based screening or Cytology (in pap)?

Answer 16

HPV based screening

Question 17

Vaccines for HPV

Answer 17

Gardasil: 6, 11, 16, 18

Cervarix: 16, 18

Gardasil-9: 6, 11, 16, 18, 31, 33, 45, 52, 58

• see slide
• vaccines made using L1: empty virus only trigger immune response w/o risk of infxn