Human Papillomaviruses and Associated Diseases

Question 1

What percent of cancers are associated with infection?

Answer 1

20%

12-15% are viral

Question 2

Structure of HPV

Answer 2

Non-enveloped double stranded DNA virus
Capsid protein L1: 360 molecules (72 X 5)
Capsid protein L2: ~ 72 molecules

Question 3

What are the oncogenes in HPV?

Answer 3

E6, E7, E8: cell proliferation, transformation, immune escape

Question 4

HPV lifecycle

Answer 4

Only infects undifferentiated proliferating basal layer cells

Produced only from fully differentiated upper layer cells

Question 5

Epidemiology of HPV

Answer 5

70-85% lifetime risk

Even bigger prevalence in developing countries

Question 6

Risk factors of HPV infection

Answer 6

Early onset intercourse
Multiple Sex Partners
History of Genital Warts
Immunosuppressive disorders
No pap smears
Oral contraceptives
Smoking

Question 7

What are the high-risk HPV types?

Answer 7

HPV16, HPV18, 31, 33, 45

Question 8

What cancers can HPV cause and what percent of them is it responsible for?

Answer 8

Cervical cancer (100%)
Head and Neck cancer (25%)
Other anogenital cancers
Non-melanoma skin cancer?

Question 9

Cytology of cervical cancer

Answer 9

ASCUS: atypical squamous cell of undetermined significance
LSIL: Low-grade squamous intraepithelial lesion
HSIL: High-grade squamous intraepithelial lesion

Question 10

How does HPV cause cancer

Answer 10

High-risk HPV is frequently integrated into host chromosome

Inhibits tumor suppressors p53 and Rb (E2F also)

Question 11

How does HPV testing work?

Answer 11

DNA detection (PCR)
mRNA detection

Question 12

Colposcopy

Answer 12

Used if pap smear is abnormal

To get a better look and take biopsies of abnormal areas

Question 13

Treatment for patients at high risk of cervical cancer

Answer 13

Surgery (Cryosurgery, Loop electrosurgical excision procedure (LEEP))

Question 14

HPV vaccines

Answer 14

Three doses

For girls and boys 11-12 years old (before sexually active)

Question 15

How to make HPV vaccine

Answer 15

Inject HPV L1 capsid protein expressing gene into yeasts, , do mass culture, purify vaccine

By only having L1 protein, get empty virus that can make immune response without risk of infection (virus-like particle)

Question 16

Limitations of HPV vaccines

Answer 16

Lack therapeutic effect
Can only reduce incidence in future generations
Don't cover all HPV genotypes
High cost 
Opposition to vaccines by some groups