Cervical Cancer

Question 1

What is the normal epithelia of the cervix and what is the cervical transition zone?

Answer 1

Ectocervix = squamous epithelium 
Endocervix = glandular (columnar) epithelium
CTZ = junction between ecto- and endocervix - physiological metaplasia

Question 2

What makes CTZ most vulnerable to HPV infection?

Answer 2

CTZ is site of physiological metaplasia and cells here are more immature therefore more prone to HPV infection

Question 3

What types of HPV are most associated with CIN/SCC of the cervix?

Answer 3

Over 150 types of HPV

Types 6 & 11 are associated with low risk (CIN1) and Types 16 & 18 with high risk (CIN2-3)

Question 4

Does HPV always lead to CIN/SCC?

Answer 4

No most infections are transient and cleared, BUT 100% of cervical cancers are associated with HPV infection

Question 5

How can HPV initiate the dysplasia-carcinoma seuqence?

Answer 5

Infects the basal layers of the epithelium of the CTZ
Contains many viral oncogenes - E6 and E7 important in pathogenesis

E6 binds to p53 to impair function - cells avoid cell cycle arrest, gene repair and apoptosis

E7 binds to Rb also allowing cells to avoid restriction points & progress through cell cycle

Cells proliferate unchecked and mutations arise leading to progression dysplasia

Question 6

What prevents HPV infection from causing dysplasia & how can this be disrupted?

Answer 6

E2 viral gene suppresses the pathogenic E6 and E7 genes.

If E2 becomes disrupted and integrated into the host genome it allows E6 & E7 effect, leading to uncontrolled proliferation and CIN 2 - 3

Question 7

What is CIN and what are the different grades?

Answer 7

CIN = cervical intraepithelial neoplasm (dysplastic premalignant lesions)

CIN 1 = low dysplasia
CIN 2 = moderate dysplasia
CIN 3 = severe dysplasia

Question 8

What is a pap smear and what does it involve?

Answer 8

Swab of cervix for sloughed cells at CZT - cytological staining performed

Can identify features of HPV infection and cell dysplasia, but not malignancy as you can’t see relationship with stroma

Results can only be interpreted as low grade (HPV/CIN1) or high grade (CIN2-3) intraepithelial lesion

Biopsy is required for confirmation

Question 9

What are signs of HPV infection?

Answer 9

Koliocytes on pap smear
Koliocytes = cells showing changes consistent with HPV infection = halo around nuclei, larger nuclei, hyperchromasia & some bi-nuclear)

Active HPV infection also detected with biomarker staining
When E7 binds Rb there is a compensatory increase in P16 which can be detected