Cervix

Question 1

Explain the importance of the SCJ in the women’s cervix?

Answer 1

It is an important junction because it is a transition zone from squamous epithelium to columnar mucus secreting epithelium. This area is highly susceptible to infections of HPV, the main cause of cervical cancer. Especially the immature squamous cells are highly susceptible to HPV. Cervical precursor lesions up the wazoo here.

Question 2

Explain how the SCJ changes with time and other influences?

Answer 2

During reproductive years, the SCJ moves out onto the ectocervix. As a woman ages, it retreats up into the endocervix.

Question 3

What is the unique metaplasia going on at the SJC?

Answer 3

There are squamous epithelial cells replacing the columnar epi cells known as squamous metaplasia.

Question 4

What is the most important factor in the development of cervical cancer?

Answer 4

high risk HPVs

Question 5

Again, big picture, what are high risk HPVs the cause of and what are low risk HPVs the cause of?

Answer 5

High risk are the cause of carcinomas where as low risk are the cause of sexually transmitted genital warts.

Question 6

What are the two HPV types that are most commonly leading to cervical cancer?

Answer 6

16 and 18

Question 7

What is the age peak of HPV infections at the cervix in women?

Answer 7

20-24

Question 8

Explain why the cervix is so susceptible to HPV infection?

Answer 8

Because it has so many immature squamous cells. HPV cannot infect mature HPV cells, only immature.

Question 9

3 characteristic features of HPV infections he wants us to know?

Answer 9

Very common and most are asymptomatic

Most are cleared by the immune system, half in 8 months and 90% in 2 years .

Question 10

There are two proteins that are the very reason why HPV is carcinogenic, what are they and what is their job?

Answer 10

E6 and E7
E6 of high risk: takes out p53 and up-regulates telomerase
E7 of low risk: takes our RB and p21 and 27

Question 11

What is the overarching thing to remember about HPV and cancer?

Answer 11

HPV is not sufficient on its own to cause cervical cancer. There are other factors that need to be present to take it from infection to cancer.

Question 12

What do we now call mild dysplasia?

Answer 12

CIN 1 and Low grade squamous intraepithelial lesion

Question 13

What do we call moderate dysplasia, severe dysplasia and carcinoma in situ?

Answer 13

Moderate: CIN 2 and High grade squamous intraepithelial lesion
Severe: CIN 3 and same
Carcinoma in situ: SINC3 and same

Question 14

What is the prognosis of LGSIL?

Answer 14

Does not progress directly to invasive carcinoma and regress by themselves.
Way more common than High grade.

Question 15

3 associations for LGSIL?

Answer 15

High level of viral replication, mild dysplasia, and most are associated with HPV 16

Question 16

Prognosis of HGSIL?

Answer 16

All are considered high risk for progression to squamous cell carcinoma. May become irreversible.

Question 17

2 associations of HGSIL?

Answer 17

All are associated with HPV 16

Increased cell proliferation, decreased or arrested maturation of cells, and low rate of viral replication.

Question 18

What is the general principle in grading between high grade and low grade lesions on histo and what is the feature we are looking for?

Answer 18

We are looking for expansion of immature cells from the basal layer. If they are in the bottom 1/3 of the epithelium, its low grade. Upper 2/3, its high grade.
The feature is atypical cells. Nuclear atypia along with perinuclear halos, or white rings around the nucleus because of viral protein E5. This is called koilocytic atypia.

Question 19

Essentially, what are we looking for in the histo?

Answer 19

HPV replication and what that is causing the host cells to do.

Question 20

With an HPV infection, where do we see the highest viral load amount?

Answer 20

In the upper half of the epithelium

Question 21

What are the HPV markers that can help us know HPV infection is going on? 2 things.

Answer 21

Because E6 and E7 viral proteins prevent cell cycle arrest, cell proliferation is booming and we see Ki 67 in the upper portion of the epithelium, which is usually in the basal layer.
Overexpression of p16.
Both Ki67 and p16 are highly associated with HPV infection.

Question 22

What is the percentage of each category for LGSIL? Regress, persist and progress to High Grade.

Answer 22

60%, 30% and 10%

Question 23

Same question for High grade. Regress, persist and progress to carcinoma?

Answer 23

30%, 60% and 10%