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Y3 repro > cervical screening > Flashcards

cervical screening Flashcards

1
Q

what viruses are implicated in human cancers

A

HBV - liver
HIV - kaposi sarcoma
EBV - lymphoma
HPV - cervical

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2
Q

how stable is HPV

A

very stable

doesn’t mutate

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3
Q

how common is HPV infection

A 
peak prevalence 15-25yrs
prevalence declines with age - clearance of virus by host immune system, less likely to acquire new infection
10% overall 
~30% prevalence in young women
lifetime risk of exposure = 80%
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4
Q

what cancers does high risk HPV cause

A 
less common cancers e.g. 
cervical - 99% cases linked to HPV
penile - 40%
vulva/vagina - 40% 
anus - 90%
mouth - 3%
oropharynx - 12%
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5
Q

how is HPV transmitted

A

close intimate contact

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6
Q

HPV infection in the cervix

A

selectively infects basal cells of the epithelial surface - needs to be some kind of microabrasion/trauma
virus replicates using host cells
final viral particles only assemble in the outermost layers in mature keratinocytes which then desquamate and release the particle

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7
Q

HPV infection in the cervix

A

selectively infects basal cells of the epithelial surface - needs to be some kind of microabrasion/trauma
virus replicates using host cells
final viral particles only assemble in the outermost layers in mature keratinocytes which then desquamate and release the particle

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8
Q

how does HPV result in disorganised cell replication and high grade lesions

what are the consequences of this?

A

viral DNA can become integrated into host DNA

if lesions aren’t detected -> can invade basement membrane and become invasive cancers

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9
Q

how long does HPV take to cause cervical cancer

A

HPV infection - 90% cleared infection
2yrs - persistent HPV infection -> viral lesions and low grade changes, can be detected, often regress back to normal
up to 5yrs - pre-cancer potential (cervical intraepithelial neoplasia)
10-20yrs - cervical cancer

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10
Q

what are the most oncogenic types of HPV

A

16 and 18
only 3% of initial infections are linked to this
CIN - 25% HPV 16 and 18
pre-cancerous lesions - 57%
cervical cancers - 70% linked to 16 and 18

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11
Q

how can cervical cancer be prevented

A

1y - HPV infection prevention

2y - detecting pre-cancerous changes and treating these before they progress

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12
Q

UK HPV immunisation programme

A

girls born after sept 1990 - bivalent vaccine HPV 16/18
sept 2012 - quadrivalent vaccine HPV 16/18/6/11
sept 2014 - 2 dose regime
2019 - boys included

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13
Q

is there a link between cervical cancer and smoking

A

yes - affects cell mediated immunity, nicotine secreted in cervical mucus

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14
Q

how does cervical screening aim to reduce the incidence of cervical cancer

A

by detecting pre-cancerous disease and treating it

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15
Q

at what age is peak incidence of CIN

A

women in their late 20s

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16
Q

is a women at higher risk because her mother had cervical cancer

A

no

linked to high risk HPV infection rather than hereditary

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17
Q

how is cervical screening managed in scotland

A

scottish cervical call recall system

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18
Q

how is the sample collected in a cervical smear

A

small plastic brush

liquid based cytology

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19
Q

where is a cervical smear taken from

A

transformation zone of the cervix - HPV infections and pre-cancerous changes will be seen here

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20
Q

pre-pubescent cervical epithelium

A

original squamous epithelium covers ectocervix

columnar epithelium lines cervical canal

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21
Q

changes to cervical epithelium during puberty

A

increased oestrogen -> increased interstitial fluid
eversion of the external os
columnar epithelium becomes exposed to the vagina
- acidic pH in the vagina is traumatic to columnar epithelium
- metaplasia of columnar epithelium

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22
Q

taking a screening sample

A 
person w/ a cervix aged 25-64y/o
from march 2020: 
- 5yrly smears
- liquid based cytology
- test for high risk HPV
- if hrHPV +ve, triage w/ cytology
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23
Q

which is more sensitive for high grade abnormalities: HPV testing or cytology

A

HPV testing

as more HPV immunised women enter the screened population, cervical disease will decrease and be more difficult to detect by cytology
HPV will be a more effective test for the future

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24
Q

does HPV vaccination prevent all cancers

A

NO

even if women have been immunised they should still attend their smear tests

25
Q

HPV test - how does it work

A

tests cervical cells
machine
identifies infection - could be transient or CIN associated
sensitive

26
Q

cytology - how does it work

A

tests cervical cells
human interpretation
identifies cellular changes: low grade (persistent infection/CIN1), high grade (CIN2/3)
specific

27
Q

lab processing of cervical samples

A

cells in the vial are tested
hrHPV test for all
if +ve (15%) - reflex cytology on same sample

28
Q

what is an HPV test

A

molecular test on cervical cell sample
identifies hrHPV E6/7 mRNA
targets 14 hrHPV types (screening doesn’t identify specific types)
works on LBC (liquid based cytology) samples
technology: hybridisation, PCR

29
Q

cervical cytology sample

A

only if hrHPV +ve:

  • microscopic assessment of cells scraped from transformation zone
  • look for abnormal cells (dyskaryosis)
  • indicate that women may have underlying CIN
30
Q

what can be seen in this cervical biopsy

A

normal stratified squamous non-keratinising epithelium
regular basement membrane
basal layer where mitosis and maturation of epithelium takes place

31
Q

nuclear features of abnormal cervical cytology - dyskaryosis

A

increased size and nuclear:cytoplasmic ratio
variation in size and shape
coarse irregular chromatin
nucleoli

32
Q

what does low vs high grade dyskaryosis reflect

A

degree of underlying CIN

low grade (+ borderline - some changes therefore can't be reported as -ve)
high grade - most likely to have CIN
33
Q

what can be seen here and what does it reflect

A

koliocytes
reflect HPV infection

peri-nuclear halo - full of viral particles
wrinkled nucleus
multinucleation

34
Q

what can be seen here and what grade

A

low grade dyskaryosis

nuclear enlargement but still a good amount of cytoplasmam
chromatin clumping but not particularly dark nuclei

35
Q

what can be seen here and what grade

A

high grade dyskaryosis
very large nucleus, large increase in nuclear:cytoplasmic ratio
marked darkening of nuclear material and clumping
notching of nuclei

36
Q

what can be seen in this cervical biopsy

A

high grade
intact BM
instead of maturation of cells towards surface there is dark staining dysplastic cells throughout full thickness of cervical epithelium

37
Q

what happens following cervical screening

A

-ve hrHPV - routine recall 5yrs

+ve hrHPV - cytology normal - repeat test 1yr to check for clearance of infection; dyskaryosis - refer to colposcopy

38
Q

colposcopy visit

A 
education and advice
colposcopy - examination of cervix: 
- magnification and light
- exclude obvious malignancy 
- use of acetic acid +/- iodine: identify limits of lesion, select biopsy site, define area to treat
39
Q

why is acetic acid used

why is iodine used

A

causes whitening of any CIN lesions - easier to identify them and their extent

iodine stains starch darkly, metaplasia/CIN don’t contain starch (normal does) and won’t stain

40
Q

what happens to pts w/ normal colposcopy

A

discharged to have smear repeated in community

41
Q

what happens to pts w/ low grade changes

A

may be discharged for repeat cytology at 1yr

if uncertain - small punch biopsy to confirm histological diagnosis

42
Q

what happens to pts w/ high grade colposcopy

A

take a biopsy to confirm diagnosis - punch biopsy to make diagnosis then have treatment OR have treatment done at that visit and treatment procedure will produce histology specimen

43
Q

management options following colposcopy

A

punch biopsy to make diagnosis
return for treatment if CIN2/3
see and treat at first visit if high grade CIN

44
Q

interpreting biopsy

A

transformation zone of cervix - looking for HPV related pathology

HPV infection
precancerous chances - CIN
cervical carcinoma

45
Q

what is the result of HPV E7 protein product

A

prevents cell cycle arrest

46
Q

what is the result of HPV E6 protein product

A

inhibits cell death

47
Q

what are the low risk HPV types and what does infection result in

A

6,11,42,44
genital warts and low grade CIN
often transient and resolve

48
Q

what are the high risk HPV types and what does infection result in

A

16, 18
31,45
persistent infection increases risk of developing high grade CIN and (more rarely) cancer

49
Q

how does HPV cause high grade CIN

A

persistent infection
viral DNA integrates into host cell genome
over-expression of viral E6 and E7 proteins
deregulation of host cell cycle

50
Q

which histology is normal and which shows CIN

A

left - normal

right - CIN

51
Q

what is cervical intraepithelial neoplasia

A

disorganised proliferation of abnormal cells in squamous epithelium (dysplasia)

lack of maturation
variation in cell size and shape 
nuclear enlargement 
irregularity
hyperchromasia
cellular disarray
52
Q

grades of CIN

A

1 - low grade dysplasia, HPV infection, will regress
2 - moderate, may regress esp in women <30y/o
3 - severe - unlikely to regress

precursor of invasive cancer

53
Q

where are most cases of CIN seen (age)

A

25-29y/o

54
Q

treatment of CIN2/3

A

women w/ CIN3 and women >30 w/ CIN2:
excise transformation zone of cervix - LLETZ (large loop excision of transformation zone)
ablate TZ of cervix - thermal/laser ablation

55
Q

follow up after treatment of CIN - why

A

confirm that treatment was effective - residual disease within 2yrs
prevent invasive cancer - recurrent disease 5% after 3-5yrs, detect occasional cancer

reassure women that her treatment has worked

increased cervical cancer risk compared w/ normal pop

56
Q

follow up after treatment of CIN - what

A

follow up LBC at 6mths for cytology and hrHPV
both -ve - return to 3yr recall
either +ve - return to colposcopy

57
Q

when is cervical screening effective

A

when it is organised and systematic and women are called and recalled

cervical cancer rates are directly linked to the quality of the prevention programmes - opportunistic vs organised

58
Q

what is the aim of cervical screening

A

reduce the risk of cervical cancer

does this by detecting hrHPV and cervical dyskaryosis

Y3 repro (47 decks)

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