Cervical cytology Flashcards

(55 cards)

1
Q

Cervical cancer

A

Type of cancer which occurs in the cervix
(cervix is the lowest part of uterus which connects to the vagina)

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2
Q

Cervical cancer is the world’s which common cancer in women

A

4th
Women with HIV are 6 times are more likely to develop cervical cancer than those without HIV

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3
Q

Which age group of women has highest inciddence rates

A

30-34
most common in women under the age of 35

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4
Q

What are preventable cancers ?
Which causes are the most preventable

A

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

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5
Q

Cancers with largest no of preventable cases

A

lung, bowel, breast, cervical, kidney

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6
Q

What are aetilogical factors causing cervical cancer

A

HPV which causes sexually transmiited infection leads to cervical cancer

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7
Q

What is HPV

A

Non-eveloped double stranded DNA virus
Over 100 subtypes with 14 types being the high risk

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8
Q

What are some high risks subtypes for cervical cancer?

A

16, 18 - account for 70% cases, 31, 33, 35, 39

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9
Q

Low risk associated subtypes

A

6, 11
HPV is a necessary but not sufficient cause of cervical cancer.

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10
Q

What is the mechanism of action of HPV

A

Viral DNA becomes intergrated into human genes.
Leads to overexpression of E6 and E7
Dysregulated cell proliferation
DNA damage builds ip overtime

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11
Q

What is the function of E6 and E7?

A

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.

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12
Q

Define normal cell cycle

A

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

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13
Q

Mechanism of action of E7?

A

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

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14
Q

Mechanism of action of E6

A

E6 binds to p53 and causes proteosomal degradation of p53
no cell cycle arrest and no apoptosis

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15
Q

What are the consequences of E6 and E7 interfering with TSG

A
  • Checkpoint dependence stopped
  • genomic instability; accumulation of oncogenic mutations
  • Increased loss of cell cycle growth/ control
    leads to cancer
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16
Q

Once HPV infects celvical epithelial cells what are th epossible outcomes

A
  • 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
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17
Q

Some risk factors for developing cervical cancer

A
  • 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
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18
Q

How has the HPV vaccination eveolved overtime?

A
  • 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

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19
Q

is it still important to attend cervical sceening if vaccinated

A

yes!
Vaccinations do not cover all strains

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20
Q

What is the use of HPV vaccination

A

provides protection from HPV subtypes not already exposed to

Provides prevention, not treatment

Femals under 25 can now get it too

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21
Q

Define screening

A

way to identify healthy people who may have increased risk of developing particular infection/condition

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22
Q

Benefits of screening

A

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

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23
Q

Risks and limitations

A

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

24
Q

How do we know what to screen for?

A

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

25
What are some of the current screening programmes
Bowel screening - all aged 50-74 Cervical - women aged 25-64 Diabetic screening - from age 12, annual eye test Breast screening - aged 50-70 Screening in pregnancy Sickle cell and thalassaemia Infectious diseases Screening in newborns PKU hearing screening
26
Cervical screening management system which plays a crucial role in managing and tracking cervical screening efforts in the UK. How does it work?
Invitations are sent out: Prior to sending invitations, a list of eligible patients is sent to the GP Reminder letters are sent out Non-responders notified to GP The aim is to achieve 80% coverage of eligible women for cervical screening programme Supported by rigorous quality assurance to ensure tests are accurate and they are provided with appropriate follow-up care. Information is provided to patients Acknowledging barriers to screening Multi-disciplinary team working
27
When is the first invigation sent out ? which age
24.5
28
Women aged 25-49 are invited after how many years for cervical screening
3
29
Women between 50-64 are invited after how many years
5
30
65+
Invitation as required for people who have had recent abnormal tests. People who have not had an adequate screening test reported since age 50 may be screened on request
31
reasons to cease from screening
if they have no cervix, women who have uterus removed due to age - over 60 with normal tests result dont require it previous raditherapy to the pelvic region - can cause cellular changes that can make cytological diagnosis difficult under the mental capacity act Patients can request screening, even if they fall outside the typical guidelines, provided they are fully informed about the decision.
32
Define squamo-columnar junction
The squamo-columnar junction (SCJ) is the area in the cervix where two types of cells meet: Squamous cells: These are flat, thin cells that line the outer part of the cervix (the part that extends into the vagina) and the vaginal canal. Columnar cells: These are taller, column-like cells that line the inner cervical canal (the passageway that leads into the uterus).
33
Why is squamo-columnar junction important-
The transformation zone is an important area in the cervix, where the squamous cells gradually replace the columnar cells. This is the region most susceptible to changes caused by human papillomavirus (HPV), which can lead to abnormal cell changes and, potentially, cervical cancer.. During a Pap smear (or cervical screening), cells from the transformation zone around the squamo-columnar junction are collected because this is where most abnormal cell changes (such as those caused by HPV) are likely to occur. HPV infections typically affect the squamo-columnar junction and the surrounding areas, which is why it’s the focus of cervical screening tests.
34
How is sample collected?
The Brush: During a cervical screening (Pap smear), a small brush is used to collect cells from your cervix (the entrance to your womb). Into the Vial: After the brush collects the cells, it’s pushed into a small container (called a vial). The brush is pushed to the bottom of the vial to spread open the bristles and release the cells it collected. Swirling the Brush: The brush is then swirled around in the vial, which helps the cells fall off the brush and mix into the liquid inside the vial. This liquid is special (an alcohol-based fixative) and helps preserve the cells so they don’t get damaged. After the cells are in the vial, the brush is thrown away in the clinical waste,
35
What does sample acceptnce policy include
Ensure the sample was taken at the correct time (within the screening interval). Check that the vial and request form have all required information. Make sure the vial isn’t leaking. Check that the broom head is properly removed from the vial. Confirm that the vial is within its expiry date. Label the sample correctly and enter it into the lab’s system (LIMS).
36
Give a name of a test which is currently used for cervical screening
Qiagen Hybrid Capture 2 High-Risk HPV DNA Test A method to detect the presence of high-risk HPV types by capturing and amplifying the DNA of the virus.
37
What is the problem with using high risk HPV testing
HR-HPV testing is better at detecting cervical abnormalities (more sensitive), but it may identify women who don’t have significant issues (less specific). A positive HR-HPV test significantly increases the risk of high-grade abnormalities or precancerous changes. A negative HR-HPV test is very reliable at ruling out cervical abnormalities (99.8% accuracy). Cytology (Pap smears) are more specific, meaning they are better at detecting actual abnormalities, but they are less sensitive and may miss some cases. Combining HR-HPV testing with cytology triage creates a stronger, more accurate screening system, especially with the introduction of HPV vaccination.
38
Use of roche cobas 8800
About 85% of samples tested by the Roche Cobas 8800 will not show HR-HPV, meaning no significant HPV infection is present, and further cytology is not needed. About 15% of samples will show HR-HPV detected, prompting a cytology slide preparation using papnicolau stain
39
What is a workflow for primary screenings.
Primary Screening by Cytologist: Cytologist screens the slide, marks abnormalities, and sends abnormal slides for further checking. Negative slides are quickly reviewed by another cytologist to confirm no issues. Checking: Senior biomedical scientists review abnormal slides and can downgrade low-grade abnormalities to negative or confirm the grade of abnormalities. Abnormal or high-grade slides are sent for a final review by a consultant. Consultant Reporting: Consultant pathologists or senior BMS report on abnormal or high-grade samples.
40
What do they look for in screening
Changes in cells which suggest preinvasive process, they do not look for cancer
41
What are 5 features of normal squamous epithelial cells (S. U. R. E.)
- uniform shape and size - rounded shape - smooth regular outlines -even chromatin pattern - normochromasia This term means that the chromatin has a normal, moderate staining intensity, meaning it doesn’t appear unusually dark or light when stained in preparation for microscopic examination. It reflects normal DNA content and activity within the nucleus.
42
The appearance of cells is affected by?
hormones like oestrogen (appear pinkish) and progesterone (purple)
43
What does atrophy refer to in context of cervical cytology
Lack of oestrogen
44
What might cause low estrogen
Can be due to menopause, post natal, breastfeeding, contraception * Cells fail to mature, predominance of parabasal type cells * Always need to check clinical details i.e if patient is on menopause, age, on HRT * Can make interpretation difficult
45
What garding system is used to grade squamous
CIN Grade Full Name Description Corresponding Bethesda Cytology Term CIN 1 Mild dysplasia Abnormal cells in lower 1/3 of epithelium LSIL CIN 2 Moderate dysplasia Abnormal cells in lower 2/3 of epithelium HSIL CIN 3 Severe dysplasia / a in situ Abnormal cells in more than 2/3, up to full thickness HSIL (refer to google docs)
46
4 Features of dyskaryosis
Nuclear enlargement with variable increase in nuclear: cytoplasmic rations Nuclear plemorphism (variable shapes) Hyperchromasia (dardker nuclei) Chromatin abnormality - may be clumped
47
N:C ration of low grade dyskaryosis
<50 % May show koilocytosis
48
N:C ration of high grade (moderate dyskaryosis)
50-75%
49
N:C ratio of severe dyskaryosis
> 75% can be single cells or sheets
50
Features of invasive squamous carcinoma
bizzare cell shapes often large numbers of severely dyskaryotic cells very large nucleoi Atypical mitosis Tumour diathesis - Tumor diathesis is a term used in cytology (especially in Pap smears or fine needle aspirates) to describe the background debris seen in smears from high-grade malignant tumors, particularly invasive carcinomas
51
Define scanty dyskarosis
Scanty dyskaryosis refers to the presence of very few dyskaryotic cells on a Pap smear — not enough to make a strong or confident interpretation, but still enough to suggest a potential abnormality. Dyskaryosis- abnormal nuclear changes in squamous cells, often due to HPV infection or precancerous lesions.
52
What are some challenges of diagnosing dyskaryosis
Lymphocytes, enodmetrial cells, histioctes and severe dyskaryosis cells all look the same, making it harder to disntinguish
53
Features of endocervical glandular cell neoplasia
Features of endocervical glandular cell neoplasia * Increased endocervical cell content * Nuclear crowding * Elongated nuclei and increased N:C ratios * Coarse nuclear chromatin * Pseudostratification, often presenting as 'strips' * Rosettes and feathering of cells at edge of groups
54
Non- cervical glandular neoplasia
* Most likely to be endometrial, occasionally ovarian – due to proximity to sample site * Less likely to pick up as a coincidental finding now, as not HPV related.
55
Features of endometrial carcinoma
3 dimensional 'scalloped' clusters of cells * Prominent nucleoli pouch Vacuolation of cytoplasm (bubbly places within the cytoplasm) * Neutrophil polymorph ingestion (Tumor cells may engulf neutrophils, showing phagocytic behavior)