Week 3 - Papilloma Viruses and Cervical Cancer Flashcards
How many women develop Cervical Cancer in the UK per year?
2800
How many cases of Cervical Cancer are there per year worldwide?
500,000
What does CIN stand for in regards to Cervical Cancer?
Cervical Intraepithelial Neoplasia
Who are the at-risk group of women?
Sexually active women between 25-45
What are the two types of Cervical Cancer?
Squamous cell cervical cancer - most common - 85% (surface cells covering the cervix)
Adenocarcinoma Cervical Cancer - Less common (Mucus-producing gland cells within endocervix)
What is CIN?
Cervical Intraepithelial Neoplasia - pre-cancerous condition
Name 3 symptoms of cervical cancer.
- Unusual discharge
- Pain
- Advanced cervical cancer:
- Haematuria
- Constipation
- Bone pain
How long does Cervical Cancer take to develop? (Generally)
Many years
How is Cervical Cancer caused?
Most cases of Cervical Cancer are in woman who have been infected with the virus.
What is the virus that causes cervical cancer?
HPV - Human Papilloma Virus
What are the main sub-types of HPV that cause cervical cancer?
HPV 16 & HPV 18 - Together linked to >70% of cancers.
HPV 31 & HPV 45 - Virus infection causes CIN
How is HPV spread?
Through sexual intercourse
Name 3 risk causes/ risk factors of Cervical Cancer.
- Infection with HPV
- Other sexually transmitted diseases- Chlamydia or HIV- weaken immune system
- Increased exposure to HPV- early sexual activity, many partners, not using barrier contraceptives
- Smoking
- Contraceptive pill- small increased risk
- No screening
What is the test for Cervical Cancer, who is it offered to and what is the process?
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.
What types of CIN are there, describe how they are categorised?
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.
What is a colposcopy?
Microscope used to look at cervix directly - see dysplastic cells
Describe Cervical Cancer Staging.
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
What is the treatment for Cervical Cancer and what must be considered?
- Local surgical excision
- Hysterectomy
- Radiotherapy
- Chemotherapy
Pathology, staging, curative and palliative patient factors must be considered.
What are the 5 year survival rates for Stage 1 vs. Stage 4?
95% (Stage 1)
15% (Stage 4)
What vaccines are available to prevent cervical cancer, how long is it effective for and when should it be give?
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.
How many HP viruses are known?
Around 100
Are they are DNA or RNA virus?
Small DNA tumour virus
What are the high risk HPV sub-types and what percentage of cervical cancer cases are they accountable for?
HPV 16 and 18 - 95% cases
Why is HPV classed as having a long latency period?
15-25 age when women become sexually active
40-50 years of age when carcinoma seen
Name 2 co-factors for cervical cancer manifestation.
Immune status
Hormonal status
Smoking
Name the genes that make up HPV.
E1 - E7
L1 - 2
Which genes in HPV are important and why?
E6/E7 - Inactivation of p53 and Rb respectively
What is the role of P53?
Guardian of the Genome, detects cellular stress and activates apoptotic pathways.
How does E6 and E7 proteins function as a oncovirus (describe the process it affects and how it affects it)?
- Cellular damage trigger P53
- E6 bind P53 - which would normally activate the P53-responsive promoter - producing Waf1
- Waf1 (P21) is a cyclin-dependent kinase inhibitor thus can stop progression of the cell cycle at G1 and S phase.
(INHIBITED)
- 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
- E2FDP1 is released from pRb by E7 which takes its place on pRb thus removing the need for CDK’s.
(PROLIFERATIVE)
