Cervial neoplasia 2 Flashcards
Why is the cervical transformation zone important for HPV infections?
It is where the HPV can access the basement membrane and infect cells
Neoplasia meaning?
New growth
What is the premalignant phase of cervical cancer?
Cervical intraepithelial neoplasia–> change in epithelium (dysplasia)
Length of time dro acquiring HPV infection to developing cancer?
3-12 yrs
How can HPV causing cancer be mitigated?
Prophylactic vaccines (everyone is vaccinated around 12), modification of risk factors
What is cervical intraepithelial neoplasia (CIN)?
Potential premalignant transformation/abnormal growth of squamous cells on the surface of the cervix
What is CIN1?
dysplasia limited to lower third of epithelium
What is CIN2?
dysplasia limited to lower two thirds of epithelium
What is CIN3?
dysplasia extending into upper third of epithelium
What is a perinuclear halo?
A clearing around the nuclei that associates w/ early HPV epithelium change
Structure of HPV?
Non-enveloped virus, single molecule of double stranded DNA
What are the three regions of HPV DNA?
Non coding regulatory region
What is the late region of the HPV virus DNA involved in?
Viral assembly and capsid proteins
What are the early regions of the HPV virus DNA involved in?
Viral replication
What does the E2 gene in HPV do?
Viral replication–> downregulated transcription of E6 and E7 genes
What are the E6 and E7 genes in HPV?
Oncogenes
What is E6?
An oncoprotein that has the ability to bind onto p53 and inactivate its function within the host cell
What is E7?
An oncoprotein that is able to inactivate the retinoblastoma protein within the host cell
Which specific cells does the HPV virus infect?
The basal epithelial cells of the cervical transformation zone
What is episomal non-productive viral repilcation?
Viral DNA is inserted into the nucleus but not into the hosts DNA
WHen during the HPV replication cycle are E6 and E7 genes activated?
Early on
What do the E6 and E7 genes in the do in the HPV journey through the epithelium?
Work to prevent terminal differentiation of the host cells–> keeps them proliferating
Why is the host cells not terminally differentiating an advantage for HPV?
It ensures that the HPV can keep replicating itself if the host cells keep proliferating
How is the HPV virus spread?
As the host cells reach the surface of the epithelium, they are shed off–> virus is released and can leave
What type of gene is p53?
tumor suppressor gene
How does p53 work?
activated by DNA damage–> causes G1 arrest by p21 activation–> results in repair of DNA damage or cell apoptosis
What does retinoblastoma protein bind onto?
E2F, a TF
Role of E2F?
A TF that is required for a cell to move from G1 into S phase of the cell cycle
How is retinoblastoma protein usually activated?
Growth factors activate cyclins, and cyclin dependent kinases phosphorylate retinoblastoma protein
What does retinoblastoma protein do once phosphorylated?
Release E2F