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Infectious Disease > HPV > Flashcards

HPV Flashcards

1
Q

What kind of virus is HPV

A

Double stranded DNA

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2
Q

How many genotypes of HPV can infect skin?

A

over 200

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3
Q

What % of cancer is caused by HPV and how many deaths per year

A

> 5% of all cancers

0.5 million deaths per year

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4
Q

what percent of cervical cancer is due to HPV

A

100% - second leading cause of cancer death in women

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5
Q

what percent of head and neck cancer is caused by HPV

A

25% - 6th leading cause cancer death in men

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6
Q

In what way is HPV linked to stratified epithelial cell differentiation?

A

Infects only undifferentiated proliferating basal cell layers

Being produced only from fully differentiated upper cell layers

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7
Q

HPV important proteins?

A

Major capsid protein L1
Minor capsid protein L2
Histone protein

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8
Q

HPV early genes

A

E1, E2, E4 and E5-7 involved in replication transcription and transformation

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9
Q

HPV late genes

A

L1 and L2
Major capsid protein
Minor capsid protein

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10
Q

HPV
early genes
E6 7 and 5 are all involved in

A

cell proliferation and transformation, immune escape

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11
Q

HPV

E1

A

Helicase, DNA replication

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12
Q

HPV

E2

A

Transcription factor, Viral genome maintenance

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13
Q

HPV

E4

A

unknown

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14
Q

HPV

LCR

A

Long control region

Promoter, DNA replication origin, Control viral gene expression

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15
Q

What is required for cancer development due to HPV?

A

Persistence of high risk HPV types

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16
Q

What constitutes a persistent infection

A

Detection of the same HPV type two or more times over 1 year

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17
Q

Mucosal HPV high risk genotypes?

A 
16
18
31
33
45
58
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18
Q

Cutaneous HPV genotypes

A 
5
8
14
17
20
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19
Q

Low risk HPV mucosal genotype

A

6

11

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20
Q

HPV Common wart
A small round tumor typically on hands and feet but often other locations
due to which genotype

A

2 and 7

21
Q

HPV Plantar wart
Occurring on the sole or toes of the foot
due to which genotype

A

HPV 1, 2, and 4

22
Q

HPV Anogenital wart
one of the most common sexually transmitted diseases, highly contagious
due to which genotype

A

HPV 6 and 11

23
Q

HPV Papillomatosis
warts form on the larynx or other areas of the respiratory tract
due to which genotype

A

HPV 6 and 11

24
Q

HPV epidermodysplasia verruciformis

A

a rare autosomal recessive disease characterized by abnormal susceptibility to HPV (various genotypes)

25
Q

High risk genotypes for cervical cancer

A

16 (50%)
18 (20%)
31, 33, 45 (25%)

26
Q

where does HPV associated cervical cancer occur?

A

99% of HPV associated cervical cancers arise within the transformation zone (area of immature metaplasia between original and current squamocolumnar junction)

27
Q

Head and neck cancer and HPV

Where does it arise?

A

cancer that arises in the squamous cells of the mouth/throat region

28
Q

Head and neck cancer is which rank in frequency

A

5th in world

6th in US

29
Q

Head and neck cancer survival rate

A

50%

30
Q

Other HPV associated cancers

  • anogenital?
  • other?
A

vaginal cancer - 50%
vulvar cancer - >50%
penile cancer 50%
anal cancer >70%

non-melanoma skin cancer - 90%
non-small cell lung cancer (Asia) - 20%

31
Q

How is HPV required for cancer development and maintenance?

A

HPV is found in cervical carcinomas
HPV oncogenes E6 and E7 are highly expressed in cancers
E6 and E7 inhibit tumor suppressors p53 and Rb
Cancer regresses when E6 and E7 are blocked

32
Q

How does HPV E6 promote cancer?

A

p53 degradation

33
Q

How does HPV E7 promote cancer?

A

interferes with pRB binding EF2 and thus interferes with arresting cell cycle - or activates genes involved in DNA replication and cell cycle progression

34
Q

High risk HPV is frequently integrated into the host chromosome - what causes uncontrollable expression of E6/E7?

A

Disruption of E2 function as a E6/7 inhibitor
Increase of viral gene transcription by host cell promoters and enhancers
More stable 3’ UTR from host chromosome

35
Q

Persistence of HPV and CIN3 increase development of?

A

squamous cell cancer

36
Q 
HPV screening recommendations 
<21
21-29
30-65
>65
A

<21 Do not screen
21-29 cytologic testing every 3 years
30-65 cytologic testing and HPV contesting every 5 years
>65 discontinue if adequate negative screening

37
Q

What is protocol if HPV positive and cytology is negative

and cytology is positive?

A

cytology negative - repeat cytology and HPV test in 6-12 months
cytology positive - colposcopy histology

38
Q

Pap smear test vs HPV test?

A

The Pap smear (papanicolaou smear) from cervical or anal scraping - shows cytological evidence of HPV infection and tissue abnormality

the HPV test

  • DNA detection
    1. end point PCR: Roche linear Array, Digene HPV genotyping
    2. real time PCR: Abbott Real Time high risk HPV test
    3. liquid phase: hybrid capture

mRNA detection
- pre-rect HPV Proofer assay, Aptima HPV assay

39
Q

Colposcopy?

A

if your Pap smear is abnormal and HPV is positive, the next step
using binocular instrument, to look at cervix
combine with biopsies for further pathological evaluation

40
Q

Cervical Cancer Progression
Normal –> Cancer
WHO
Bethesda

A

Normal - Cervical Intraepithelial neoplasia I - CIN2/3 - Cancer

Normal - Atypical Squamous Cell of undetermined significance - Low grade squamous intraepithelial lesion - high grade squamous intraepithelial lesion - cancer

41
Q

Treatment of Cervical cancer?

A

Surgery
Cryosurgery or
Loop Electrosurgical Excision Procedure (LEEP)

42
Q

Treatment for genital warts?

A

Prescription cream

  • Podofilox or Condylox
  • Imiquimod or Aldara
43
Q

HPV therapeutics in development

A

vaccines - therapeutic

target Oncogenes E6/7

44
Q

Gardasil
Vaccine component and production
Genotypes covered

A

VLPs of L1 protein made in yeast with aluminum adjuvant

HPV6/11/16/18

45
Q

Cervarix
Vaccine Component and production
Genotypes covered

A

VLPs of L1 protein made in insect cells with AS04 adjuvant

HPV16/18

46
Q

Gardasil 9
Vaccine component and production
Genotypes covered

A

VLPs of L1 protein made in yeast with aluminum adjuvant

HPV6/11/16/18 + HPV31/33/45/52/58

47
Q

Vaccine dosing?

A

2 for 9-14 years
3 for 15-26
Before sexually active

48
Q

How are vaccines for HPV made?

A

Isolate HPV L1 capsid protein expressing genes (only L1 not L2)
Can trigger immune response without risk of infection

Infectious Disease (5 decks)

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