Pathology of Cervix, Vagina, and Vulva 1

Question 1

What is the area of transition of the cervix?

Answer 1

The transition from the glandular epithelium of the internal cervix to the squamous epithelium on the ectocervix

Question 2

What is squamous metaplasia of the cervix?

Answer 2

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

Question 3

What area of the cervix is uniquely sensitive to HPV?

Answer 3

transformation zone

Question 4

What are the most important risk factors for cervical cancer?

Answer 4

• HPV related
  
  • Multiple sexual partners
  • High parity
  • Early initiation of sexual activity
• Smoking

Question 5

What is the main etiologic factor for driving squamous dysplasia and how does it occur?

Answer 5

• 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

Question 6

What are the low and high risk HPV types?

Answer 6

• 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