Cervical Screening (HRP Session) Flashcards
12% of human cancers are caused by viruses.
Which virus is implicated?
- HBV
- HIV
- EBV
- HPV - we are going to focus on this one, this can result in precancer of the cervix so lens itself to cervical screening
How common is HPV infection?
peak prevalence 15-25yrs
prevalence declines with age
10% overall
~30% prevalence in young women
lifetime risk of exposure 80% from serological studies
High-risk HPV causes other less common cancers such as what?
HPV infection in the cervix - what is the process?
Early HPV infections may be accompanied by mild changes in the epithelium
An abnormal growth of squamous cells detectable on smear is called a squamous intraepithelial lesion (SIL). Such changes may be low grade (LSIL) or high grade (HSIL), depending on how much of the cervical epithelium is affected, and how abnormal the cells appear
Abnormal cells in the cervix detected by biopsy and histological examination are classified as cervical intraepithelial neoplasia (CIN). Graded 1 to 3 according to the proportion of cervix affected
what is the process of HPV leading to cervical cancer?
cervical intraepithelial neoplasia - CIN
how is primary prevention done?
UK HPV Immunisation Programme
1 Sept 2008
Girls born after 1 September 1990 - Bivalent vaccine HPV16/18
Sept 2012 - Quadrivalent vaccine HPV 16/18/6/11
Sept 2014 - 2 dose regime
Boys included 2019
what oercentage uptake did we need to aim for?
80% but we got more than that in scotland
what do you know about HPV?
- HPV infection is ____ __________
- Most HPV infections are cleared by the _________ _______ (little clinical input)
- Most _______ cancers are associated with HPV
- HPV very ________ causes cancer
- In UK, 12 year olds are immunised against HPV_____ to reduce the risk of cervical cancer
very common
immune system
cervical
rarely
16/18
Flora, 25 year old P0 is receives an invitation to book an appointment for cervical screening at her GP practice:
- She is lower risk as only she is only 25 years old
- She is lower risk as she has no symptoms
- She is higher risk as she smokes
- She is higher risk because her mother had cervical cancer at age 35 years
- She is higher risk as she did not have the HPV vaccine
3.
screening is about screening asymptomatic people
what is the Scottish Cervical Call Recall System (SCCRS)?
what is the community health index?
unique number
first 6 digits are patients date of birth
what is the uptake of cervical screening in scotland?
older women are better attending
cervical screening uptake is higher in the least deprived
She makes an appointment with the practice nurse for a cervical screening test
how is it taken
collected using plastic broom
in a liquid based cytology
what is the epithelium of the cervix?
want to sample in the transformation zone
in ouberty there is everison of the intenral os of the cervix and the columnar epithelium becomes exposed to the vaginal
white is the columnar/glandular epithelium is undergoing metaplasia and now have a new squamo-columnar junction and this is the zone that is the transformation zone
Flora was invited for a smear test because:
- Her post code and CHI identify her as female, age 25 and deprived
- Her CHI identifies she is female and age 25
- Her CHI identifies she has not had a smear test recorded yet on SCCRS
- Her CHI identifies that she is aged 25 and sexually active
- Her CHI identifies that she is a person with a cervix and age 25
2
Case continued:
Flora makes an appointment with the practice nurse for a cervical screening test
She gets a letter 2 weeks later to advise her that there are minor changes and she will be seen at colposcopy for further investigation
how is taking a screening sample done?
Person with a cervix* aged 25-64 years
From March 2020:
5 yearly smears
Liquid Based Cytology (LBC)
Test for high risk HPV
If hrHPV positive; triage with cytology
how has cervical screening changed?
Prior to the change to HPV-based screening in 2020, all samples had a cytology slide made which was examined under the microscope (see left of diagram) - by a human. Since the changeover, all samples now have a HPV test – done by a machine (shown on right). Only the HPV-positive ones now have a cytology test. Therefore from 2020, cervical screening is largely done by machines
Why did we change to HPV testing for cervical screening?
HPV testing is more sensitive than cytology for high grade abnormalities
As more HPV-immunised women enter the screened population, cervical disease will decrease and will be more difficult to detect by cytology. HPV will be more effective test for the future.
If the HPV test is negative, the woman’s chance of developing cervical cancer in the next 5 years is very small, allowing a 5 year screening interval for all women regardless of age.
The smear is taken in the ____ way, so the cervical sampling experience for women will ___ ______
Remember…..HPV vaccination doesn’t prevent all _______ and even if women have been __________, they should still attend for their smear tests!
same
not change
cancers
immunised
how do these tests differe? - HPV test and cytology
Laboratory Processing of Cervical Samples - what is the process?
Cells in the vial are tested
Hr HPV test (all)
If positive (15%) reflex cytology
What is an HPV test?
Molecular test on cells sampled from cervix
Identifies high risk HPV E6/7 mRNA
Targets 14 High risk HPV types (but screening test does not identify specific HPV types)
Works on LBC (liquid based cytology) samples
Technology: Hybridisation & PCR
Cervical cytology sample:
Only if high risk ________
_________ assessment of cells scraped from the __________ zone
Look for _________ cells (dyskaryosis)
indicate that woman may have underlying _______ __________ _________ - CIN
not a ________ test, a screening test and more _______ the cytology is, the more likely there is that there is an abnormality
HPV +ve
Microscopic
transformation
abnormal
cervical intraepithelial neoplasia
diagnostic
abnormal
cervical cytology sample
The majority of cells present are mature squamous cells scraped from the surface of the metaplastic squamous epithelium of the transformation zone.
Immature squamous metaplastic cells may also be obtained from areas where the process of metaplasia is less complete e.g. adjacent to the squamocolumnar junction
CYTOLOGY of the CERVIX abnormal = ______________
DYSKARYOSIS
CYTOLOGY of the CERVIX abnormal = DYSKARYOSIS
Abnormal cells may be few
what are the nuclear features?
increased size and nuclear:cytoplasmic ratio
variation in size, shape and outline
coarse irregular chromatin
nucleoli
Graded low or high grade dyskaryosis - reflects degree of underlying ___
Low grade (+ borderline)
High grade (this is what we are intrested in)
CIN
what is shown here?
KOILOCYTES - reflect HPV infection
perinuclear halo apperance
Koilocytes, also known as halo cells, are a type of epithelial cell that develops following a human papillomavirus (HPV) infection
what is shown here?
low grade dyskaryosis
what is shown here?
high grade dyskaryosis
High grade dyskaryosis – underlying CIN3
what happens next weather you are positive or negative?
Negative for hrHPV – routine recall 5 years
Positive for hrHPV:
- Cytology normal; repeat test 1 year
- Dyskaryosis: refer to colposcopy
Flora gets an invitation to book a colposcopy appointment at her local hospital. The reason is:
- Her HPV test is positive
- She has high risk HPV and low grade dyskaryosis
- She had low grade dyskaryosis or BNA on cytology
- Her test was unsatisfactory or failed
- Her smear taker thought her cervix looked abnormal
2
need to have some sort of dyskaryosis to have been refered to colposcopy
what happens on your frist visit to colposcopy?
watch again
Education and advice
Colposcopy:
- Magnification and light to see cervix
- Exclude obvious malignancy
- Use of acetic acid (causes whitening of any CIN lesions) =/- Iodene:
- Identify limits of lesion
- Select biopsy site
- Define area to treat
what is shown here?
normal colposcopy image of the cervix
can see the new squamous-columnar juction
Clinical picture - low-grade change
this cervix has had acentic acid appleid to it
CIN 1
Clinical picture - high-grade change
capillary vessel patterns
mossaic effect
whata re the options for management?
Punch biopsy to make a diagnosis
Return for Treatment if CIN2/3
if high grade then can offer to do treatment on that first clinic visit
“See and treat” at first visit
PATHOLOGY of the CERVIX - what are pathologiests looking for
patholgist is trying to identify the Transformation zone of cervix: HPV related pathology
we ask the pathologist is it:
- HPV infection
- precancerous changes cervical intraepithelial neoplasia (CIN)
- cervical carcinoma
how does HPV infect the transformation zone?
Infects basal layer cells
Utilises host for replication
As host cell matures, different viral genes expressed
HPV histology - what are Koilocytosis?
Cells with wrinkled nucleus and perinuclear halo
Multinucleation
Human Papilloma Virus:
what are low risk types and what do they cause?
Low Risk types - 6, 11, 42, 44 (et al)
Genital warts and Low grade CIN
Often transient and resolve
Human Papilloma Virus:
what are high risk types and what do they cause?
High Risk types - 16, 18, 31, 45 (et al)
Persistent infection increases risk of developing
High grade CIN and (more rarely) cancer
How does HPV cause high grade CIN?
High risk HPV type and Persistent infection:
- Viral DNA integrates into host cell genome
- overexpression of viral E6 and E7 proteins
- deregulation of host cell cycle
HIstology of CIN
CIN3
Neoplastic cells or undifferentiated cells fill full thickness of epith here, no normal differentiated cells seen = CIN3
When undiffer cells occupy 2/3 of thickness and only top layers show maturation to medium size cells = CIN2
If undiff cells only occupy lowest 1/3 of epith and surface cells can mature to big flat cells = CIN1
what is Cervical Intraepithelial Neoplasia?
Invisible to naked eye
Disorganised proliferation of abnormal cells in squamous epithelium (dysplasia) - Lack of maturation, variation in cellular size and shape, nuclear enlargement, irregularity, hyperchromasia (darkly staining nuclei), cellular disarray
CIN 1: low grade dysplasia – will regress
CIN 2: moderate dysplasia – may regress
CIN 3: severe dysplasia – unlikely to regress
Precursor of invasive cancer
the different types of CIn affect how much oft he epithelium?
Low-grade neoplasia (CIN 1) refers to dysplasia that involves about one-third of the thickness of the epithelium
CIN 2 refers to abnormal changes in about one-third to two-thirds of the epithelial layer
CIN 3 (the most severe form) describes a condition that affects more than two-thirds of the epithelium
what age is most cases of CIN seen?
25-29
what is the treatment of CIN2/3
Excise TZ* of cervix - LLETZ (loop electrosurgical excision procedure - The abnormal tissue is removed using a thin wire loop that is heated electrically)
Ablate TZ of cervix - Thermal Ablation, Laser ablation
* = Transformation zone
what follow-up happens after the treatment of CIN?
To confirm that treatment was effective - Residual disease with in 2 years
To prevent invasive cancer:
- Recurrent disease 5% after 3-5 years
- Detect occasional cancer
To reassure the woman that her treatment has worked
After treatment of CIN there is an Increased risk of cervical cancer compared with the normal population
Follow-up LBC at 6 months for cytology and high risk HPV:
- Both negative – return to 3 year recall
- Either positive – return to colposcopy
What is the aim of cervical screening?
- Detect cervical dyskaryosis
- Reduce the risk of cervical cancer
- Detect CIN
- Prevent Cervical Cancer
- Reduce high risk HPV infections
2
does this by detecting high risk HPV adn cervical dyskaryosis, aim is not to detect CIN itself
what to remember:
___ is single most important cause of CIN and cervical cancer
Screening detects high risk ___ and ________ changes which are asymptomatic
Screening allows treatment of pre-invasive changes (CIN) to prevent ______
HPV __________ + cervical screening to maximise protection
Even if immunised, anyone with a ______ still needs to be offered cervical screening
HPV
HPV
pre-invasive
cancer
vaccination
cervix
