Cervical cytology Flashcards
(55 cards)
Cervical cancer
Type of cancer which occurs in the cervix
(cervix is the lowest part of uterus which connects to the vagina)
Cervical cancer is the world’s which common cancer in women
4th
Women with HIV are 6 times are more likely to develop cervical cancer than those without HIV
Which age group of women has highest inciddence rates
30-34
most common in women under the age of 35
What are preventable cancers ?
Which causes are the most preventable
A person’s risk of developing a certain cancer depends on factors like age, genetics, exposure to risk factors.
Smoking is largest single preventable cause
Overweight and obesity, the 2nd biggest
Alcohol
Cancers with largest no of preventable cases
lung, bowel, breast, cervical, kidney
What are aetilogical factors causing cervical cancer
HPV which causes sexually transmiited infection leads to cervical cancer
What is HPV
Non-eveloped double stranded DNA virus
Over 100 subtypes with 14 types being the high risk
What are some high risks subtypes for cervical cancer?
16, 18 - account for 70% cases, 31, 33, 35, 39
Low risk associated subtypes
6, 11
HPV is a necessary but not sufficient cause of cervical cancer.
What is the mechanism of action of HPV
Viral DNA becomes intergrated into human genes.
Leads to overexpression of E6 and E7
Dysregulated cell proliferation
DNA damage builds ip overtime
What is the function of E6 and E7?
These proteins interfere with key tumor suppressor pathways:
E6 promotes degradation of p53, a critical regulator of DNA repair and apoptosis.
E7 inactivates retinoblastoma protein (pRb), leading to uncontrolled entry into the cell cycle.
Define normal cell cycle
G1-phase - cells increase in size
G1/S checkpoint- regulated by Retinoblastoma protein. pRB binds to E2F so it isnt prematurely pushed into S phase
S phase- Duplication of chromosome, DNA replication
G2 phase - Cell continues to grow and prepare for mitosis. checks that dna replication is undamaged
G2/ M checkpoint - regulated by p53- if DNA is damaged, it halts the cell cycle. if the damage is too severe, it causes apoptosis to prevent the damage to living cells
Mechanism of action of E7?
Normal -
pRb is active (hypophosphorylated).
It binds to E2F, a transcription factor.
This prevents E2F from activating genes needed for DNA synthesis.
Cancer -
E7 binds (inactivates pRB) and phosphorylates pRB, activating E2F transcription factors.
E2F activates genes required for DNA replication, pushing the Cell into S-phase prematurely
Mechanism of action of E6
E6 binds to p53 and causes proteosomal degradation of p53
no cell cycle arrest and no apoptosis
What are the consequences of E6 and E7 interfering with TSG
- Checkpoint dependence stopped
- genomic instability; accumulation of oncogenic mutations
- Increased loss of cell cycle growth/ control
leads to cancer
Once HPV infects celvical epithelial cells what are th epossible outcomes
- Clearance of virus within 3 years
- progression to low-grade lesions (mild dysplasia)
- progression to high grade lesion (significant precancerous changes)
If High grade not treated, invasion of abnormal cells into deeper tissues can occur causing cervical carcinoma
Some risk factors for developing cervical cancer
- sexual activity from an ealry age
high no of sexual partners
early age of first pregnancy
long term use of contraceptives
Women who are immunosupressed (organ transplant)
Smoking
Exposure to Diethylstilboestrol (DES) in utero refers to a situation where a fetus is exposed to DES, a synthetic estrogen that was prescribed to pregnant women to prevent miscarriages and other pregnancy complications.
Not attending screening
How has the HPV vaccination eveolved overtime?
- 2008 only given to girls aged 12- 13
Only vaccinated against subtype 16 and 18
2009- providing vaccination upto 18 age in girls
2019 - boys given vaccination to prevent HPV related cancers in males.
Screening was introduced as well
2022- Gardisal 9 is now used for vaccination as it provides protection again 9 subtypes
is it still important to attend cervical sceening if vaccinated
yes!
Vaccinations do not cover all strains
What is the use of HPV vaccination
provides protection from HPV subtypes not already exposed to
Provides prevention, not treatment
Femals under 25 can now get it too
Define screening
way to identify healthy people who may have increased risk of developing particular infection/condition
Benefits of screening
provides early detection before symptoms occur
if detected early, more effective treatment
reduces the chances of developing conditions or its complications
prevention of deaths from the condition
able to make informed decisions about health
Risks and limitations
not 100% accutate may lead to false positive or negative
may lead to difficult decisions needed to be made
Increased anxiety
even if the results are negative, a person may still develop the conditio n
How do we know what to screen for?
Within the UK, an expert group called the UK National Screening
The Committee (UKNSC) advises which screening programmes to offer.
Condition- should be an important health problem with recognisable early stage
Test- simple, safe and acceptable.
Treatment- effective, leading to improved outcomes
Cost considerations- Costs of case finding need to be economically balanced