cervical screening Flashcards
what viruses are implicated in human cancers
HBV - liver
HIV - kaposi sarcoma
EBV - lymphoma
HPV - cervical
how stable is HPV
very stable
doesn’t mutate
how common is HPV infection
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%
what cancers does high risk HPV cause
less common cancers e.g. cervical - 99% cases linked to HPV penile - 40% vulva/vagina - 40% anus - 90% mouth - 3% oropharynx - 12%
how is HPV transmitted
close intimate contact
HPV infection in the cervix
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
HPV infection in the cervix
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
how does HPV result in disorganised cell replication and high grade lesions
what are the consequences of this?
viral DNA can become integrated into host DNA
if lesions aren’t detected -> can invade basement membrane and become invasive cancers
how long does HPV take to cause cervical cancer
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
what are the most oncogenic types of HPV
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
how can cervical cancer be prevented
1y - HPV infection prevention
2y - detecting pre-cancerous changes and treating these before they progress
UK HPV immunisation programme
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
is there a link between cervical cancer and smoking
yes - affects cell mediated immunity, nicotine secreted in cervical mucus
how does cervical screening aim to reduce the incidence of cervical cancer
by detecting pre-cancerous disease and treating it
at what age is peak incidence of CIN
women in their late 20s
is a women at higher risk because her mother had cervical cancer
no
linked to high risk HPV infection rather than hereditary
how is cervical screening managed in scotland
scottish cervical call recall system
how is the sample collected in a cervical smear
small plastic brush
liquid based cytology
where is a cervical smear taken from
transformation zone of the cervix - HPV infections and pre-cancerous changes will be seen here
pre-pubescent cervical epithelium
original squamous epithelium covers ectocervix
columnar epithelium lines cervical canal
changes to cervical epithelium during puberty
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
taking a screening sample
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
which is more sensitive for high grade abnormalities: HPV testing or cytology
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
does HPV vaccination prevent all cancers
NO
even if women have been immunised they should still attend their smear tests
HPV test - how does it work
tests cervical cells
machine
identifies infection - could be transient or CIN associated
sensitive
cytology - how does it work
tests cervical cells
human interpretation
identifies cellular changes: low grade (persistent infection/CIN1), high grade (CIN2/3)
specific
lab processing of cervical samples
cells in the vial are tested
hrHPV test for all
if +ve (15%) - reflex cytology on same sample
what is an HPV test
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
cervical cytology sample
only if hrHPV +ve:
- microscopic assessment of cells scraped from transformation zone
- look for abnormal cells (dyskaryosis)
- indicate that women may have underlying CIN
what can be seen in this cervical biopsy
normal stratified squamous non-keratinising epithelium
regular basement membrane
basal layer where mitosis and maturation of epithelium takes place
nuclear features of abnormal cervical cytology - dyskaryosis
increased size and nuclear:cytoplasmic ratio
variation in size and shape
coarse irregular chromatin
nucleoli
what does low vs high grade dyskaryosis reflect
degree of underlying CIN
low grade (+ borderline - some changes therefore can't be reported as -ve) high grade - most likely to have CIN
what can be seen here and what does it reflect
koliocytes
reflect HPV infection
peri-nuclear halo - full of viral particles
wrinkled nucleus
multinucleation
what can be seen here and what grade
low grade dyskaryosis
nuclear enlargement but still a good amount of cytoplasmam
chromatin clumping but not particularly dark nuclei
what can be seen here and what grade
high grade dyskaryosis
very large nucleus, large increase in nuclear:cytoplasmic ratio
marked darkening of nuclear material and clumping
notching of nuclei
what can be seen in this cervical biopsy
high grade
intact BM
instead of maturation of cells towards surface there is dark staining dysplastic cells throughout full thickness of cervical epithelium
what happens following cervical screening
-ve hrHPV - routine recall 5yrs
+ve hrHPV - cytology normal - repeat test 1yr to check for clearance of infection; dyskaryosis - refer to colposcopy
colposcopy visit
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
why is acetic acid used
why is iodine used
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
what happens to pts w/ normal colposcopy
discharged to have smear repeated in community
what happens to pts w/ low grade changes
may be discharged for repeat cytology at 1yr
if uncertain - small punch biopsy to confirm histological diagnosis
what happens to pts w/ high grade colposcopy
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
management options following colposcopy
punch biopsy to make diagnosis
return for treatment if CIN2/3
see and treat at first visit if high grade CIN
interpreting biopsy
transformation zone of cervix - looking for HPV related pathology
HPV infection
precancerous chances - CIN
cervical carcinoma
what is the result of HPV E7 protein product
prevents cell cycle arrest
what is the result of HPV E6 protein product
inhibits cell death
what are the low risk HPV types and what does infection result in
6,11,42,44
genital warts and low grade CIN
often transient and resolve
what are the high risk HPV types and what does infection result in
16, 18
31,45
persistent infection increases risk of developing high grade CIN and (more rarely) cancer
how does HPV cause high grade CIN
persistent infection
viral DNA integrates into host cell genome
over-expression of viral E6 and E7 proteins
deregulation of host cell cycle
which histology is normal and which shows CIN
left - normal
right - CIN
what is cervical intraepithelial neoplasia
disorganised proliferation of abnormal cells in squamous epithelium (dysplasia)
lack of maturation variation in cell size and shape nuclear enlargement irregularity hyperchromasia cellular disarray
grades of CIN
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
where are most cases of CIN seen (age)
25-29y/o
treatment of CIN2/3
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
follow up after treatment of CIN - why
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
follow up after treatment of CIN - what
follow up LBC at 6mths for cytology and hrHPV
both -ve - return to 3yr recall
either +ve - return to colposcopy
when is cervical screening effective
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
what is the aim of cervical screening
reduce the risk of cervical cancer
does this by detecting hrHPV and cervical dyskaryosis
