Pathology of Cervix, Vagina, and Vulva 1 Flashcards
Describe the etiologic role that high risk HPV plays in the development of invasive cervical carcinoma.
1
Q
What is the area of transition of the cervix?
A
The transition from the glandular epithelium of the internal cervix to the squamous epithelium on the ectocervix
2
Q
What is squamous metaplasia of the cervix?
A
Upon onset of menarche, the glandular epithelium on the external face of the cervix is replaced with squamous epithelium - area known as the transformation zone
3
Q
What area of the cervix is uniquely sensitive to HPV?
A
transformation zone
4
Q
What are the most important risk factors for cervical cancer?
A
-
HPV related
- Multiple sexual partners
- High parity
- Early initiation of sexual activity
- Smoking
5
Q
What is the main etiologic factor for driving squamous dysplasia and how does it occur?
A
-
High risk HPV infection
- viral DNA, extremely common
- Most cases, immune system able to clear infection without dysplaisa
- Some cases, infection becomes persistent and can result in dysplasia that evolves over the course of years to invasive cervical carcinomas
-
Mechanism
- dysregulates cell cycle
- uses two viral proteins
- E6 - accelerates degradation of p53, impairs DNA repair and apoptosis
- E7 - disrupts E2F-Rb dimers, which promotes re-entry into the cell cycle
- P16 is upregulated as E2F-Rb dimers are disrupted, leads to uncontrolled cell replications
6
Q
What are the low and high risk HPV types?
A
-
Low risk
- types 6 and 11
- associated with transient infections and genital warts
- virtually never result in severe dysplasia or invasive cervical carcinoma
- does not integrate into host genome - episomes
-
High risk
- types 16 and 18 are most common (also 31 and 33)
- much more likely to persist and promote dysplasia
- also responsible for invasive carcinomas in the vagina, vulva, and head and neck