Week 3 - Papilloma Viruses and Cervical Cancer

Question 1

How many women develop Cervical Cancer in the UK per year?

Answer 1

2800

Question 2

How many cases of Cervical Cancer are there per year worldwide?

Answer 2

500,000

Question 3

What does CIN stand for in regards to Cervical Cancer?

Answer 3

Cervical Intraepithelial Neoplasia

Question 4

Who are the at-risk group of women?

Answer 4

Sexually active women between 25-45

Question 5

What are the two types of Cervical Cancer?

Answer 5

Squamous cell cervical cancer - most common - 85% (surface cells covering the cervix)

Adenocarcinoma Cervical Cancer - Less common (Mucus-producing gland cells within endocervix)

Question 6

What is CIN?

Answer 6

Cervical Intraepithelial Neoplasia - pre-cancerous condition

Question 7

Name 3 symptoms of cervical cancer.

Answer 7

1. Unusual discharge
2. Pain
3. Advanced cervical cancer:
4. Haematuria
5. Constipation
6. Bone pain

Question 8

How long does Cervical Cancer take to develop? (Generally)

Answer 8

Many years

Question 9

How is Cervical Cancer caused?

Answer 9

Most cases of Cervical Cancer are in woman who have been infected with the virus.

Question 10

What is the virus that causes cervical cancer?

Answer 10

HPV - Human Papilloma Virus

Question 11

What are the main sub-types of HPV that cause cervical cancer?

Answer 11

HPV 16 & HPV 18 - Together linked to >70% of cancers.

HPV 31 & HPV 45 - Virus infection causes CIN

Question 12

How is HPV spread?

Answer 12

Through sexual intercourse

Question 13

Name 3 risk causes/ risk factors of Cervical Cancer.

Answer 13

1. Infection with HPV
2. Other sexually transmitted diseases- Chlamydia or HIV- weaken immune system
3. Increased exposure to HPV- early sexual activity, many partners, not using barrier contraceptives
4. Smoking
5. Contraceptive pill- small increased risk
6. No screening

Question 14

What is the test for Cervical Cancer, who is it offered to and what is the process?

Answer 14

The Papanicalou Test - Smear test offered to women between 25-64 years of age.

Detects pre-invasive step.

Vaginal canal opened with speculum and cells are collected from the ‘transformation zone’ - area where outer squamous cervical cells meet inner glandular endocervical cells.

Question 15

What types of CIN are there, describe how they are categorised?

Answer 15

CIN 1, 2 & 3

Increase in number = increase in severity.

Cells are identified as being dyskaryotic - increase in the size of nucleus due to irregular nuclear chromatin - more severe dyskaryosis the more severe the CIN

CIN’s are also differentiated by their penetration to the surface - affected cells start from the basal layer and progress further to the surface epithelium as severity increases.

Question 16

What is a colposcopy?

Answer 16

Microscope used to look at cervix directly - see dysplastic cells

Question 17

Describe Cervical Cancer Staging.

Answer 17

Stage I: carcinoma confined to cervix

Stage IA: invasive cancer identified only microscopically

Stage IB Clinical lesion confined to cervix

Stage II: Extends beyond cervix but not to pelvic wall

Stage III: Extended on to pelvic sidewall

Question 18

What is the treatment for Cervical Cancer and what must be considered?

Answer 18

1. Local surgical excision
2. Hysterectomy
3. Radiotherapy
4. Chemotherapy

Pathology, staging, curative and palliative patient factors must be considered.

Question 19

What are the 5 year survival rates for Stage 1 vs. Stage 4?

Answer 19

95% (Stage 1)

15% (Stage 4)

Question 20

What vaccines are available to prevent cervical cancer, how long is it effective for and when should it be give?

Answer 20

Two vaccines.

Gardasil - HPV 16, 18 and 6 and 11 (6 and 11 cause genital warts)

Cervarix: HPV 16 and 18 (70% of cases)

Effective for 6 years.

Must be given before viral exposure.

Question 21

How many HP viruses are known?

Answer 21

Around 100

Question 22

Are they are DNA or RNA virus?

Answer 22

Small DNA tumour virus

Question 23

What are the high risk HPV sub-types and what percentage of cervical cancer cases are they accountable for?

Answer 23

HPV 16 and 18 - 95% cases

Question 24

Why is HPV classed as having a long latency period?

Answer 24

15-25 age when women become sexually active

40-50 years of age when carcinoma seen

Question 25

Name 2 co-factors for cervical cancer manifestation.

Answer 25

Immune status
Hormonal status
Smoking

Question 26

Name the genes that make up HPV.

Answer 26

E1 - E7

L1 - 2

Question 27

Which genes in HPV are important and why?

Answer 27

E6/E7 - Inactivation of p53 and Rb respectively

Question 28

What is the role of P53?

Answer 28

Guardian of the Genome, detects cellular stress and activates apoptotic pathways.

Question 29

How does E6 and E7 proteins function as a oncovirus (describe the process it affects and how it affects it)?

Answer 29

1. Cellular damage trigger P53
2. E6 bind P53 - which would normally activate the P53-responsive promoter - producing Waf1
3. Waf1 (P21) is a cyclin-dependent kinase inhibitor thus can stop progression of the cell cycle at G1 and S phase.

(INHIBITED)

4. Cyclins bound to CDK phosphorylate pRB-E2FDP1 complex (1 phosphate group) - this releases E2FDP1 and further phosphorylating pRb so it has 5 phosphate groups - the whole point is to release E2FDP1 from pRb
5. E2FDP1 is released from pRb by E7 which takes its place on pRb thus removing the need for CDK’s.

(PROLIFERATIVE)