Human Papilloma Virus

Question 1

What is papilloma virus infection limited to?

Answer 1

Epithelial cells of the skin and mucosa

Question 2

hPV causes?

Answer 2

Warts (benign tumors)

Question 3

Can hPV lead to malignancy?

Answer 3

Yes

Question 4

Most common place for hPV caused cancers? Where else can it occur?

Answer 4

Cervical

Penile, Anal, Oral, and Neck

Question 5

What are condylomas?

Answer 5

Prominent anogenital warts

Question 6

Most common cause of anogenital warts (condylomas)? Risk of cervical cancer?

Answer 6

hPV 6 and 11

- Low

Question 7

What common cause of subclinical papilloma infection(SPI)? Risk of cervical cancer?

Answer 7

hPV 16 and 18

- High

Question 8

What is the role of the viral proteins, E6 and E7, in the development of cancer?

Answer 8

They bind and ultimately remove/inactivate two tumor suppressor proteins, p53 and Rb

Question 9

How is hPV transmitted?

Answer 9

Through direct contact with warts or contaminated fomites

Question 10

When do most people become infected with hPV?

Answer 10

Early in life

Question 11

What keeps people infected with hPV from having common warts all the time?

Answer 11

The innate immune system

Question 12

What is the most common STD in the US?

Answer 12

hPV

Question 13

Tx of warts?

Answer 13

Physical destruction of the wart

- Recurrences can occur

Question 14

Why do recurrences occur with common warts?

Answer 14

Virus remains in the basal layer of the skin

Question 15

What does the vaccine consist of?

Answer 15

L1 capsid protein

Question 16

Structure of hPV?

Answer 16

A nonenveloped icosahedral capsid ds-DNA genome - 8 kilobase pairs –> small end of DNA virus genome complexity

Question 17

What is the icosahedral capsid composed of?

Answer 17

Two proteins - L1 and L2

Question 18

How is the icosahedral capid assembled?

Answer 18

Self-assembly

Question 19

Why is it important that hPV is non-enveloped?

Answer 19

It contributes to the stability of the virus particles on the skin and fomites

Question 20

What happens in cells permissive to growth?

Answer 20

Virus replicates and is released by lysing cells

Question 21

What happens in non-permissive cells?

Answer 21

Late gene expression does not occur and instead of virus production –> infection leads to the formation of transformed cells

Question 22

What are transformed cells?

Answer 22

Cells capable of producing tumors

Question 23

Where is the genome maintained in benign tumor cells?

Answer 23

extrachromosomally - 40-50 copies

Question 24

Where is the genome maintained in malignant tumor cells?

Answer 24

Portion of the virus genome is integrated into the host chromosome

Question 25

Features of transformed cells?

Answer 25

Immortal No longer contact inhibited in cell culture No longer require serum-derived growth factors in cell culture No longer anchorage-dependent for growth in cell culture Can lead to tumor formation in syngeneic animals

Question 26

What do the early (E) genes of hPV encode? Important E proteins?

Answer 26

Proteins needed for replication and transformation; | E6 and E7

Question 27

What does E6 bind to? E7?

Answer 27

p53 - leads to its degradation | Rb (retinoblastoma protein) - inactivates it

Question 28

The binding of E6 to p53 and E7 to Rb leads to?

Answer 28

Uncontrolled growth of the cells --> tumor formation

Question 29

In malignant tumors, where only a portion of the virus genome is integrated into the host chromosome, what is always intact?

Answer 29

E6 and E7

Question 30

In malignant tumors, are E6 and E7 expressed at elevated levels?

Answer 30

Yes

Question 31

Where does the virus initially infect? These are considered?

Answer 31

The germinal cells in the basal layer of the skin. | Non-permissive cells - virus particles are not produced and the cells are transformed

Question 32

As the germinal cells mature and migrate to the skin surface, what happens?

Answer 32

As the germinal cells differentiate into keratinized epithelia, the cells become permissive and produce progeny

Question 33

What is laryngeal papillomas?

Answer 33

Chronic, benign warts in the respiratory tract that generally first appear before the age of 5 - B/c of the associated respiratory distress, up to 3% of patients die annually

Question 34

What can you detect with a Pap smear?

Answer 34

Koilocytotic squamous epithelial cells --> indicate hPV infection

Question 35

Co-factors in the development of cervical cancer?

Answer 35

Smoking and co-infection with HSV

Question 36

When are laryngeal papillomas acquired? Most common cause?

Answer 36

at birth in 50% of cases | hPV 6 and 11

Question 37

Can hPV be routinely grown in cell culture?

Answer 37

No

Question 38

How is dx of common, plantar, and anogenital warts made?

Answer 38

Clinical appearance

Question 39

What is the next step after an abnormal pap smear?

Answer 39

Colposcopy

Question 40

What does the vaccine gardasil protect against?

Answer 40

Infection with hPV 6, 11, 16, and 18