Cervical Cytology Flashcards
What are the criteria for the introduction of screening programmes
- the condition should be an important health problem - the natural history should be known
- the test should be simple safe and acceptable with known cutoff point for test values
- the treatment should be effective, leading to better outcomes with evidence based policies on who should receive treatment
- the screening programme should be known to be effective in reducing mortality or morbidity
What is the aetiology of cervical cancer?
- Rare outcome of STI
- Linked to Human Papilloma Virus (low risk types 6&11, high risk types 16&18)
- HPV DNA can be found in all invasive cervical cancer specimens
What are some risk factors of cervical cancer
- persistent infection with HPV or STI
- sexual activity from young age
- women with kate pregnancies or >5 full term pregnancies
- condoms only offer limited protection
Smoking decreases number of lanerghans cells in the cervix reducing ability to process virus
What stages happen in between normal and the cancer stage in the cervix
Low grade squamous intraepithelial lesion —> high grade squamous intraepithelial lesion
Describe the human papilloma virus
Non-enveloped
DsDNA
Circular genome (approx 8kb pairs)
Most encode 8 major proteins
How long is the average incubation period
3 weeks to a year
Can HPV infection be latent or assymptimatic
Yes, possibly years before appearance of genital warts or abnormalities
Some will be transient and may never be detected
What proteins from HPV play a massive role in immortality and malignant transformation of infected cells
E6&E7
Characteristics of low risk HPV 6 & 11
Lead to benign cervical changes and genital warts
Characteristics of high risk HPV types 16 & 18
Precancerous cervical changes
Cervical cancer
Anal and other cancers
True or false: most women are infected at some time
True
True or false: the immune system usually clears a HVP infection
True, usually, not always
What is the pathology of persistent HPV infection
Leads to loss of maturation of cervical epithelium (disrupts normal cell cycle)
Keratinocyte differentiation retarded
What are the first stages of the triage pathway
See if the pt. displays borderline/low grade dyskaryosis then do a HR-HPV test
What is the next move if the HR-HPV test is negative
Pt. returned to routine recall because it’s likely the cause of problem is non-high-risk HPV infection or not a clinically significant amount of HPV
What are some benefits of a triage
Reduces need for multiple repeat tests, women see colposcopy sooner
What’s the next move if the HR-HPV test is positive
Women referred to colposcopy
What is a test of cure
Used to assess the risk of women who test negative at follow up are at very low risk of Cervical Intraepithelial Neoplasia having residual of recurrent disease
What is standard protocol after CIN 3 detected in colposcopy
Annual follow up cytology for 10 years —> returned to routine recall
Where are cervical cytology samples taken from?
The transformation zone
What is the transformation zone
The zone between the new and old squamo-columnar junction
A method acquiring a cervical sample
Using a brush then transfer the sample to alcohol
True or false: mild dyskaryosis is heavily linked to HPV positive
True: the initial pilot study for HOV triage showed 83% showing dyskaryosis were HOV positive
Name a benefit of test if cure for cervical screening
Allows majority of women to be r freed back to routine recall directly
How does HPV attack
Micro trauma to squamous epithelial of transformation zone allows HPV to attach tit he nasal cells. The genome is then release into the cell remaining as an extra-chromosomal element until cEll reaches surface
What happens after a cell is infected with the HPV genome
The extra-chromosomal elements are packaged into virions that are lost from the surface during desquamation
What happens in the non latent case of HOV infection
Genome is incorporated, increased expression of viral protein E6 and E7 that interacted with cellular proteins to induce proliferation, eventually immortalisation and neoplastic transformation of HPV infected cells
Describe the epithelial of the cervix
Lined in 1 cell thick columnar glandular epithelial layer then the vagina lines in squamous cells, where they meet is the squamo-columnar junction
What area of the cervix is the most susceptible to abnormalities
Transformation zone
Why is the transformation zone particularly vulnerable
Because the changes in hormones make the cervix swell and expose the T zone to the vaginal are making it open to infection
What are the two methods of cervical sample preparation
Thinprep and surepath (BD)
Describe the characteristics if the thin prep sample method
Methanol based
Filtration method
Ubstained sample
Describe characteristics of Surepath cervical sampling method
Ethanol based preservative
Density gradient and sedimentation
Stained slide produced by automation
True or false: cervical screenings aim to look for cancer
False: they aim to prevent it
What cells does squamous epithelium consist of
From surface to base: superficial cells, intermediate cEll’s, parabasal cells, basal cells
Explain what screening sample adequacy is
Does the sample have an adequate number of visible squamous cells for screwing - >4500
How long do you need to leave it in between samples from a patient
3 months
Can the appearance of cells be affected by hormones
Yes
What are some features of dyskaryosis
High nuclear to cytoplasm ratio
Hyperchromasia (darker nuclei)
Chromatic irregularity
Irregularity in form and outline of nuclear membrane
Where in the endometrium does CIN 1 affect
Infected cells occupy lower third of basal cells
Where in the endometrium does CIN 2 affect
Lower TWO thirds of basal cells
Where in the endometrium does CIN 3 affect
Majority of basaloid cells —> carcinoma
What are the typical nuclear to cytoplasmic ratio reference values for low-grade dyskaryosis
Ratio<50%
What are the typical nuclear to cytoplasmic ratio reference values for high-grade (moderate) dyskaryosis
50
What are the typical nuclear to cytoplasmic ratio reference values for high-grade (sever) dyskaryosis
Ratio>75%
What are some changes to cells due to HPV
- Minor nuclear abnormality
- dyskeratosis (abnormal keratinisation)
- parakeratosis (normal keratinisation in abnormal places)
- koilocytosis - red cells with abnormal nuclei and hard edged clear spaces surrounding the nuclei pathognamonic If HPV infection
Why do you have to look at nuclei features to confirm its dyskaryosis
Because it has lookalikes such as atrophy
Describe the appearance (cytology) of invasive squamous carcinoma cells
High grade dyskaryosis
Loose cluster of pale (cytoplasm) cells with enlarged nuclei (dark), coarse chromatin and a thickened nuclear membrane
What is colposcopy
The microscopic examination is the cervix with the use of stains to see cells in the TZ
What are the procedures of a colposcopy
Examine cervix, wipe off mucus, apply 5% acetic acid for 2 mins, aptly green filter and aqueous iodine.
Biopsy if necessary
What are the chances of regression for CIN 1
Most likely will regress
What are the chances of regression for CIN 2
50%
What are the chances of regression for CIN 3
0%, needs treatment
Name a couple treatments for premalignancy of cervical cells
Loop excision - extract bad cells with a loop tool
Cryotherapy - gun like tool that freezes (kills) malignant cells
What are the symptoms of cervical malignancy
Vaginal bleeding at any time other than period
vaginal discharge with unpleasant smell
Discomfort or pain during sex
Where is cervical cancer at stage 1/4
Just in neck of the womb
Where is cervical cancer at stage 2/4
Begun to spread outside neck of womb into surrounding tissues
Where is cervical cancer at stage 3/4
Spread away from cervix and into surrounding structures in pelvic area
Where is cervical cancer at stage 4/4
Advanced cancer. Spread to other body organs outside cervix and womb
How do you treat stage 1 cervical cancer
Cone biopsy
How do you treat stage 2+ cervical cancer
Hysterectomy
What are some limitations of screening
Not 100% effective, false negative rate up to 40%, sampling and screening errors.
However HPV triage and test of cure have improved detection significantly
Who must the HPV screening program be offered to
All girls up to 18 years old
What product is now used as the vaccination against cervical cancer (HPV infection)
Gardasil A’s protects against HPV 6 and 11 and genital warts aswell
True or false: Boys have to have HPV vaccinations too
True: as of September 2019 all boys aged 12-13 because it’s connected to anal Carcinoma too
How effective is Gardasil
Clinical trials show 100% effective at PREVENTING infection of 6,11,16&18 ONLY
How is the HPV vaccination administered
2 injections within 6-24 months of each other
What is a benefit of HR-HPV over Cytology
More sensitive
What is a benefit of Cytology over HR-HPV
Gives less false positives
What is an argument for the extending of screening intervals
HrHPV and Cytology decreases CIN 3 or worse and cervical cancer by 40 and 30% as opposed to cytology. Low incidence OF CIN3 or worse 3 years after screening supports the extension of interval time
How many sentinel sites are there for HOV screening
6
