HPV, warts, cervical cancer

Question 1

HPV structure

Answer 1

non-enveloped dsDNA virus. Capsid proteins L1 and L2

Question 2

List the early vs late genes for HPV

Answer 2

early: replication (E1), trxn (E2) and transformation genes (E5-7). Late: major (L1) and minor capsid proteins (L2)

Question 3

Which HPV genes are oncogenes

Answer 3

E5, E6 and E7. All code for cell proliferation and transformation genes.

Question 4

What is the long control region of HPV

Answer 4

Promoter region- DNA replication origin and controls viral gene expression

Question 5

HPV life cycle

Answer 5

HPV Life Cycle is Linked to Stratified Epithelial Cell Differentiation. It only infects undifferentiated proliferating basal layer cells and it is released by the fully differentiated upper layer cells

Question 6

HPV transmission

Answer 6

Sex, genital-genital, manual-genital, oral-genital (condoms don’t fully protect). Mother to newborn (vertical transmission, rare) or fomites (surgical gloves, clothes, etc, not well documented)

Question 7

risk factors for HPV

Answer 7

early intercourse (before age 20), multiple partners, hx of genital warts, immunosuppressive disorders, failure to receive pap smears, long term use of contraceptives, smoking

Question 8

Define a persistent HPV infection

Answer 8

Detection of same HPV type two or more times over 1 year. Persistence of high risk HPV is crucial for cancer development. Factors associated with persistent infection: >30 yrs, infection with multiple HPV types, immune suppression

Question 9

Normal HPV course

Answer 9

In women 15-25 years of age, ~80% of HPV infections are transient and cleared within 1 year (Median duration of infection = 8 months)

Question 10

2. Identify high and low risk HPVs

Answer 10

Mucosal HPV- high risk: 16, 18, 31,33, 35, 39, 45, 51, 52, 56, 58, 59. low risk: 6, 11, 40, 42, 43, 44. Cutaneous HPV: 1, 2, 5, 7, 8, 14, 17, 20, 47

Question 11

describe common wart and HPV types associated with it

Answer 11

Verruca vulgaris- small, rough tumor typically on hands and feet but often other locations. HPV 2 and 7

Question 12

Describe plantar wart and HPV types associated with it

Answer 12

verruca plantaris- occurs on sole or toes of foot. HPV 1, 2, 4

Question 13

Describe anogenital warts and HPV types associated with them

Answer 13

condyloma acuminatum- sexually transmitted disease, highly contagious. HPV 6, 11 and others

Question 14

describe respiratory papillomatosis and HPV types associated with it

Answer 14

warts form on larynx or other areas of respiratory tract. HPV 6 and 11

Question 15

Epidermodysplasia verruciformis

Answer 15

rare autosomal recessive disease
characterized by abnormal susceptibility to HPV
(various genotypes). Growths occur on the skinrare autosomal recessive disease
characterized by abnormal susceptibility to HPV
(various genotypes). Growths occur on the skin

Question 16

Which HPVs are associated with cervical cancer

Answer 16

HPV16 (50%), HPV 18 (20%), HPV 31, HPV 33, HPV 45 (25%)

Question 17

Where do HPV cervical cancers arise

Answer 17

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

Question 18

List the cancers associated with HPV

Answer 18

cervical (100%), head and neck (25%), vaginal (50%), vulvar (50%), penile (50%), anal (50%), non-melanoma skin cancers (90%), non-small cell lung cancers (20% asia)

Question 19

describe cervical cancer progression (WHO histopath)

Answer 19

normal > cervical intraepithelial neoplasia 1 (CIN1) > CIN2/3 > cancer

Question 20

describe cervical cancer progression (Bethesda classification)

Answer 20

normal > atypical squamous cell of undetermined significance (ASCUS) > low-grade squamous intraepithelial lesion > high grade squamous intraepithelial lesion > cancer

Question 21

What percentage of those infected with HPV will develop cancer, clear the infection or progress to CIN2/3

Answer 21

80% will be infected and clear the infection. 10% will progress to CIN2/3 after 7-15 years

Question 22

HPV oncogenes functions

Answer 22

E6 and E7 are highly expressed in cancers. They inhibit p53 (E6) and Rb (E7). Cancer regresses when they are blocked

Question 23

functions of p53 and Rb

Answer 23

p53 causes cell cycle arrest and apoptosis in response to cellular stress and DNA damage. Rb binds to E2F and causes cell cycle arrest by stopping trxn of genes for cell cycle progression.

Question 24

What causes uncontrollable expression of HPV E6/E7

Answer 24

1. Disruption of E2 functions as a E6/E7 inhibitor
2. Increase of viral gene transcription by host cell
   promoters and enhancers. 3. More stable 3’ UTR from host chromosome

Question 25

Screening for HPV

Answer 25

pap smear/HPV test- if negative repeat HPV test in 3-5 yrs. If HPV positive, but cytology negative, repeat cytology and HPV test in 6-12 mos. If HPV positive and cytology positive, colposcopy/histology

Question 26

Methods used for HPV test

Answer 26

1. DNA detection- PCR or liquid phase. 2. mRNA detection- pre-Tect HPV proofer assay

Question 27

describe colposcopy

Answer 27

Uses a binocular colposcope to look at cervix

Question 28

Who gets screened for HPV

Answer 28

65: discontinue screening if adequate number of negative results previously

Question 29

Treatment of HPV

Answer 29

1. surgery! -cryosurgery, loop electrosurgical excision procedure. 2. genital warts- creams. Podofilox or condylox. Imiquimod or aldara. 3. vaccines. 4. Target HPV oncogenes E6 and 7

Question 30

Compare the HPV vaccines- what is it, what does it protect against, when was it approved

Answer 30

1. Gardasil: Virus Like Particles of L1 protein made in yeast with aluminum adjuvant. Protects against HPV 6, 11, 16 and 18. 2006 approved. 2. Cervarix: VLPs of L1 protein made in insect cells with AS04 adjuvant. Protects against HPV 16, 18. 2009 approved

Question 31

HPV vaccine dosing

Answer 31

three doses, age 11-12 up to 26 years

Question 32

Limitations of HPV vaccines

Answer 32

VLPs only induce antibody response, doesn’t cover HPV genotypes causing 30% of cancers, high cost, opposition by social/religious groups