Human Papilloma Virus Flashcards
What is papilloma virus infection limited to?
Epithelial cells of the skin and mucosa
hPV causes?
Warts (benign tumors)
Can hPV lead to malignancy?
Yes
Most common place for hPV caused cancers? Where else can it occur?
Cervical
Penile, Anal, Oral, and Neck
What are condylomas?
Prominent anogenital warts
Most common cause of anogenital warts (condylomas)? Risk of cervical cancer?
hPV 6 and 11
- Low
What common cause of subclinical papilloma infection(SPI)? Risk of cervical cancer?
hPV 16 and 18
- High
What is the role of the viral proteins, E6 and E7, in the development of cancer?
They bind and ultimately remove/inactivate two tumor suppressor proteins, p53 and Rb
How is hPV transmitted?
Through direct contact with warts or contaminated fomites
When do most people become infected with hPV?
Early in life
What keeps people infected with hPV from having common warts all the time?
The innate immune system
What is the most common STD in the US?
hPV
Tx of warts?
Physical destruction of the wart
- Recurrences can occur
Why do recurrences occur with common warts?
Virus remains in the basal layer of the skin
What does the vaccine consist of?
L1 capsid protein
Structure of hPV?
A nonenveloped icosahedral capsid ds-DNA genome - 8 kilobase pairs –> small end of DNA virus genome complexity
What is the icosahedral capsid composed of?
Two proteins - L1 and L2
How is the icosahedral capid assembled?
Self-assembly
Why is it important that hPV is non-enveloped?
It contributes to the stability of the virus particles on the skin and fomites
What happens in cells permissive to growth?
Virus replicates and is released by lysing cells
What happens in non-permissive cells?
Late gene expression does not occur and instead of virus production –> infection leads to the formation of transformed cells
What are transformed cells?
Cells capable of producing tumors
Where is the genome maintained in benign tumor cells?
extrachromosomally - 40-50 copies
Where is the genome maintained in malignant tumor cells?
Portion of the virus genome is integrated into the host chromosome
Features of transformed cells?
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
What do the early (E) genes of hPV encode? Important E proteins?
Proteins needed for replication and transformation;
E6 and E7
What does E6 bind to? E7?
p53 - leads to its degradation
Rb (retinoblastoma protein) - inactivates it
The binding of E6 to p53 and E7 to Rb leads to?
Uncontrolled growth of the cells –> tumor formation
In malignant tumors, where only a portion of the virus genome is integrated into the host chromosome, what is always intact?
E6 and E7
In malignant tumors, are E6 and E7 expressed at elevated levels?
Yes
Where does the virus initially infect? These are considered?
The germinal cells in the basal layer of the skin.
Non-permissive cells - virus particles are not produced and the cells are transformed
As the germinal cells mature and migrate to the skin surface, what happens?
As the germinal cells differentiate into keratinized epithelia, the cells become permissive and produce progeny
What is laryngeal papillomas?
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
What can you detect with a Pap smear?
Koilocytotic squamous epithelial cells –> indicate hPV infection
Co-factors in the development of cervical cancer?
Smoking and co-infection with HSV
When are laryngeal papillomas acquired? Most common cause?
at birth in 50% of cases
hPV 6 and 11
Can hPV be routinely grown in cell culture?
No
How is dx of common, plantar, and anogenital warts made?
Clinical appearance
What is the next step after an abnormal pap smear?
Colposcopy
What does the vaccine gardasil protect against?
Infection with hPV 6, 11, 16, and 18
