Cervical Cancer Flashcards
What is HPV?
Human papilloma virus
What does HPV cause infections of?
Skin & mucous membranes
How is HPV spread?
HPV strains spread through childhood from direct skin-to-skin contact may lead to common warts (e.g. veruccas)
Other strains are sexually transmitted
How are the sexually transmitted strains of HPV split up?
Low risk groups - cause benign anogenital warts
High risk/oncogenic group - account for maj of cervical cancers
What are the low risk strains of HPV?
HPV 6/11
What are the high risk strains of HPV?
16/18
How can we prevent HPV?
Active HPV vaccination in teenagers
How do you cure HPV infection?
You cannot
It is persistent after primary infection (in infected basal cells of the mucosal skin)
What is the lifetime exposure of HPV?
Up to 75%
When is the peak prevalence of HPV infection?
15-25y
What % of cervical cancers are caused by HPV?
> 99%
What other cancers can HPV cause?
Penile, vulva/vaginal, mouth, oropharynx
What is the aetiology of HPV infection leading to cervical cancer?
Micro-abrasion of cervical lining –> HPV invades basal cells where they stay for many years
Virus begins to mix with cells DNA & replicates & invades other cells (can be picked up as pre-cancerous)
Cells become damaged & disorganised –> high risk lesion
High grade pre-cancerous lesion grows & occupies whole thickness of skin
All cells infected & completely disorganised –> invasive cancer that can break through the skin & spread to other parts of the body
Early HPV infection may be accompanied by _______
Mild changes in epithelium
What is an abnormal growth of squamous cells known as?
Squamous intraepithelial lesion (SIL)
Can be high grade/low grade depending on how much of the epithelium is effected & how abnormal the cells look
Abnormal cells in the cervix can be detected by _____ and are classified as _________ graded:
Biopsy/histology
Cervical intraepithelial neoplasia
Graded 1 to 2 based on how much of the cervix is affected
Persistent infection with __________ is req for the development of cervical cancer
ONCOGENIC HPV types
How do the CIN lesions progress?
CIN 1 may regress or progress to CIN 2/3 or cervical cancer
What happens to most low grade SILs?
They clear within 6-12m (probably due to immunological intervention)
Small % progress to high grade SIL (which is assoc. with CIN 2/3 at biopsy)
What % of CIN 2/3 progress to carcinoma?
40%
Which strain of HPV has the most oncogenic potential?
16
What cohort are vaccinated against HPV?
Girls born after 1st September 1990
What is in the HPV vaccine?
Now quadrivalent
HPV 16, 18, 11, 6
So prevents genital warts too
When is the HPV vaccine given to girls?
12-13 years in school
Girls who have not been vaccinated have the same level of protection as those who aren’t. Why is this?
Such high uptake of vaccine
What is involved in the process of cervical screening?
Receive invitation via mail if registered with a GP practice
Done by Scottish Cervical Call Recall System
Smear taken, details entered on SCCRS
Slides stained & screened
Cytology puts result on SCCRS
During screening - small brush is used to collect some cells from the surface of the cervix which can be sent for liquid cytology
What is the endocervix?
Luminal cavity within cervix forming a passage between the external and internal Os
What sort of epithelium covers the endocervix?
Glandular, columnar
What covers the ectocervix?
Non-keratinising squamous epithelium
What is the squamocolumnar junction?
Junction between the squamous and columnar epithelium
How does the position of the SCJ change over time?
Birth/premenarchal - close to external os (original SCJ)
Reproductive age - variable distances from external os
Post-menopausal - SCJ recedes into endocervix (not visible)
During pregnancy/OCP use - cervix enlarges & may be able to see SCJ on surface of cervix
What happens to the columnar epithelium when it is exposed to the vagina?
Undergoes normal metaplasia into squamous epithelium due to acidity of vagina
Why is the vagina so acidic?
Lactobacilli produce lactic acid which contributes to low pH of vagina
What is the distance between the original SCJ and the new SCJ known as?
Transformation zone
How will a woman find out her smear results?
She will be contacted after 2 weeks to find out her results
What happens if a woman has an abnormal smear?
She will be invited for colposcopy
What woman are screened for cervical changes?
25-64y
5 yearly
How are smears checked?
Liquid based cytology
Test if high risk HPV
If +ve triage with cytology
What is the HPV test?
Molecular test on cells from cervix
Identifies high risk HPV viral DNA/RNA
Any high risk type –> type specific genotyping
(Use LBC samples and use hybridisation/PCR)
Currently who gets a cervical cytology sample looked at? What does it involve?
ALL - but from 2020 only HPV +ve
Microscopic assessment of cells scraped from transformation zone looking for abnormal cells (dyskaryosis) to see if woman has CIN - stained with PAP
What is the problem with the transformation zone?
Contains immature cells & due to the unstable hormonal environment it is particularly vulnerable to infection
How do you classify dyskaryosis?
Increased size and nuclear:cytoplam ratio
Variation in size, shape & outline
Course irregular chromatin
Nucleoli
Multinucleation
Cells with wrinkled nucleus & perinuclear halo
How is dyskaryosis graded?
Low (+ borderline) - persisting infection/CIN1
High - likely to progress to cancer (CIN2/3)
What are koliocytes?
Squamous epithelial cells that have undergone structural changes as a result of HPV infection
If you get a negative result for high risk HPV what is the protocol?
Routine recall in 5 years
If you get positive for high risk HPV what is the protocol?
Cytology normal - repeat test in 1y
Dyskaryosis - refer for colposcopy
What is colposcopy?
Procedure to look at upper vagina, cervix & lower uterus
Uses magnification and light
Will exclude obvious malignancy
What chemical is used to help see precancerous changes?
How is it helpful?
Acetic acid +/- iodine
Can find limits of lesion, & where to biopsy
What should you do if you see a precancerous lesion on colposcopy?
Biopsy to make diagnosis
Rx if CIN2/3 or can see & treat at first visit
Summarise how a HPV infection leads to dyskaryosis
HPV infects basal cells in transformation zone via microtears
Uses host for replication
As host cell matures, different viral genes expressed
At top layer fully assembled viruses shed
E6 protein product inhibits cell death
E7 protein product inhibits cell cycle arrest
Overexpression of viral E6 and E7 –> dysregulation of host cell cycle
What is CIN?
Cervical intraepithelial neoplasia
Visible to naked eye
= disorganised proliferation of abnormal cells in squamous epithelium (lack of maturation, variation in cellular size & shape, nuclear enlargement, irregularity, hyperchromia, cellular disarray)
How do you diagnose CIN?
Biopsy
What is CIN 1?
Undifferentiated cells only occupy lowest 1/3rd of epithelium (surface cells can mature)
Low grade dysplasia - should regress
What is CIN 2?
Undifferentiated cells occupy 2/3rd thickness & only top layers show maturation to medium sized cells
Mod dysplasia, may regress
What is CIN3?
Neoplastic/undifferentiated cells full thickness of epithelium
No normal differentiated cells
Severe dysplasia, unlikely to regress
How do you Rx CIN?
LLETZ
Thermal coagulation
Thermal ablation
What is LLETZ?
Large loop excision of transformation zone
Diathermy used to cut area of abnormal cells away
Why is follow up of CIN after Rx req?
To confirm Rx effective & no cancer present now
Reassurance
When do we follow up CIN?
After Rx
LBC at 6m for cytology & high risk HPV
Both neg - return to recall
Either positive - colposcopy
Do people with CIN have an increased risk of cervical cancer?
Yes
As compared to general pop
What is the peak age of cervical cancer?
45-55y
What is cervical cancer assoc with?
HPV (16/18) Multiple partners Early age at first intercourse Older partner of age Cigarette smoking
Higher incidence in deprived areas (more smoking, less likely to come for screening)
What are the symptoms of cervical cancer?
Abnormal vaginal bleeding PCB IMB/PMB Discharge Pain (lower back, pelvis, during sex)
How do you diagnose cervical cancer?
Clinical
Screen detected
Biopsy
What does cervical cancer look like histologically?
Tumour cells invade from epithelium into underlying stroma
What are the types of cervical cancer?
80% are squamous cell carcinoma
More rarely can get adenocarcinoma (endocervical)
What is the staging for cervical cancer?
Stage 1A - invasive cancer identified only microscopically
IA1 - <3mm depth and 7mm or less diam (=microinvasive)
IA2 5mm+ x 7mm
IB - tumour confined to cervix
Stage 2 - spread to upper vagina (upper 2/3rd)
Stage 3 - lower vagina, pelvis
Stage 4 - rectum, ladder
Metastatic - pelvic nodes, liver, lung, bone
How can you stage cervical cancer?
EUA (Ex under anaesthesia)
PET-CT
MRI
How do you Rx stage 1a1 cervical cancer?
Type 3 excision of cervical TZ or hysterectomy
How do you Rx stage 1b-2a cervical cancer?
Radical hysterectomy/radio + chemo
How do you Rx stage 2b-5?
Chemo + radio
What is involved in a radical hysterectomy?
Exploration of pelvic + para-aortic space
Removal of uterus, cervix, upper vagina, parametria, pelvic nodes
Ovaries conserved!
What kind of radio can you do?
External beam x 20 fractions
Caesium 24h insertion
What chemo can you give for cervical cancer?
5 cycles of cisplatin
