Flashcards in Diseases of the female genital system 1 Deck (76):
What is meant by VIN?
Vulval intraepithelial neoplasia
What is meant by CIN?
Cervical intraepithelial neoplasia
Intraepithelial neoplasia refer to what kind of growth?
What is meant by CGIN?
Cervical glandular intraepithelial neoplasia
What is meant by VaIN?
Vaginal intraepithelial neoplasia
What is meant by AIN?
Anal intraepithelial neoplasia
Intraepithelial neoplasia of the female genital system can be caused by which virus?
What is dysplasia?
Earliest morphological manifestation of multistage process of neoplasia, its in situ disease (ie. non-invasive), shows the cytological features of malignancy without invasion
Is dysplasia treatable?
Yes as it is not invasive
Does HPV infection always cause harm?
No, in most women HPV will not cause long term harm and will be cleared by the immune system
The lifecycle of HPV is linked to what?
How many subtypes of HPV are there?
>100, based on DNA sequence - different types infect different tissues
Genital HPVs are grouped into what 2 categories?
1) Low risk
2) High oncogenic risk
Low risk HPVs are associated with what?
Lower genital tract warts (condylomas = benign squamous neoplasms) and low grade intraepithelial neoplasms
High risk HPVs are associated with what?
Hihg grade intraepithelial neoplasma and invasive carcinomas
Which are the 2 most common low risk HPVs?
6 and 11
Which are the 2 most common high risk HPVs?
16 and 18
What percentage of cervical cancers contain HPV?
99.7% (types 16 and 18 associated with 70% of all cervical cancers)
Why is all cervical cancer not prevented by HPV vaccine?
Current HPV vaccine only vaccinates against the 2 low risk types (6 and 11) and the 2 most common high risk types (16 and 18) - other types can cause cervical cancer
What 2 types of genes are possessed by HPVs and what is the role of each?
Early genes - expressed at onset of infection, control viral replication and in oncogenic viruses are involved in cell transformation
Late genes - encode capsid proteins
High risk HPVs intergrate into the host chromosomes, which 2 proteins does it upregulate the expression of?
E6 and E7
What does the protein E6 do in cells infected by high risk HPV, what effect does this have?
Binds to and inactivates P53
P53 normally mediated apoptosis in response to DNA damage so as a result of its inactivation get accumulation of genetic damage
What does the protein E7 do in cells infected by high risk HPV, what effect does this have?
Binds to an inactivates RB1 which is a tumour suppressor gene which controls G1/S checkpoint in cell cycle thus through its inactivation you have dysregulation of cell proliferation
What are the 2 molecular pathways for the development of VIN?
1) Classical/ warty/ baseloid
2) Differentiated VIN
The classical/ warty/ baseloid VIN is related to what and most common in which group?
Most common in younger people
Related to HPV infection
Is the classical VIN graded?
Yes Graded 1-3
The differentiated VIN is related to what and occurs in which group?
Occurs in older people
NOT related to HPV - occurs in chronic dermatoses (inflammatory skin conditions) especially Lichen Sclerosus
Is differentiated VIN graded?
What percentage of cases of VIN recur and what is a predictor of recurrence?
Positive margins (ie. neoplastic cells extend beyond the edge of the tissue resected) predicts recurrence
What is the difference in rates of progression to invasive Ca in untreated and treated VIN?
Treated VIN (surgery) - 4-7%
Untreated VIN - 87%
In which group is spontaneous regression of VIN most likely to occur?
Young, post partum women
Progression to invasive Ca is most likely to occur in which group?
Post menopausal or immunocompromised
What is the most common type of vulval cancer, accounting for 90% of vulval cancer?
Squamous cell carcinoma
Squamous cell carcinoma of the vulva is associated with what 2 conditions?
VIN (in people under 60)
Inflammatory dermatoses (in people over 70, particularly Lichen sclerosis)
What percentage of women with symptomatic Lichen Sclerosus go on to develop squamous cell carcinoma of the vulva?
How does a vulval squamous cell carcinoma appear macroscopically?
Eroded plaque or ulcer
Vulval squamous cell carcinoma spreads very predictably, to what 3 places does it spread?
1) Locally to involve vagina and distal urethra
2) To ipsilateral inguinal LNs
3) To contralateral inguinal LNs, deep iliofemoral LNs
What is a sentinel lymph node?
The first lymph node to which a cancer metastasises - can be identified by injecting tumour with a radioactive tracer
The risk of lymph node mets can be related to what factor relating to the tumour?
Depth of invasion - lymph node mets for a tumour with
What staging system is used to stage vulval squamous cell carcinoma and what 5 stages does it involve?
FIGO staging system, stages 1,2,3,4A,4B
What is the overall 5 years survival for vulval squamous cell carcinoma?
Name 2 other common vulval tumours?
1) Malignant melanoma
2) Extramammary Paget's disease
Malignant melanoma accounts for what percentage of vulval cancers?
What is the mean age of incidence vulval malignant melanoma?
Where is a common sight of spread of vulval malignant melanoma and how does it spread?
Commonly spreads to urethra
Lymph node and haematogenous spread are both common
Lymph node involvement correlates with what factors in vulval malignant melanoma?
Depth of invasion
What is Paget's disease?
An in situ adenocarcinoma of the squamous mucosa
What is the recurrence rate of Paget's disease?
Tend to recur following excision
How does Paget's disease appear macroscopically?
Pruritic/ burning/ eczematous patch
What can Paget's disease develop into?
What percentage of vulval cancers does Paget's disease account for, what is the mean age of incidence?
5% of vulval cancers
Mean age = 80
In Paget's disease of the vulva is there usually an underlying tumour?
No - in only 5% is there regional malignant disease (Bladder, cervix, anus)
How does the epithelium of the cervix change with menarche and what develops?
Ectocervix is lined by squamous epithelium
Cervical canal is lined by simple columnar epithelium
At menarche there is a physiological bulking of the cervix (increase in connective tissue component) and this causes a mechanical eversion of the squamocolumnar junction
The columnar epithelium now on the ectocervix cannot withstand the acidic environment of the vagina and undergoes squamous metaplasia
This area undergoing metaplasia is known as the transition zone - this area is vulnerable and is often where CIN develops
What happens to the transition zone of the cervix post menopause, why does this create a problem for cervical cancer screening?
Cervix shrinks and some of transition zone retracts up the cervical canal
This transition zone is a high risk area for development of CIN thus is the area screened - CIN may be missed if it occurs in the area contained within the cervical canal
What is CIN, is it graded?
Pre-invasive stage of cervical SCC (thing we are trying to catch on screening) - it is graded according to increasing abnormality
There are 3 grades of CIN, why is grade 1 not treated?
It has a regression rate of 60% - standard treatment is thus to watch and wait and see if it goes away by itself
What is the treatment for grade 2 and 3 CIN?
For what 5 reasons is the cervical screening programme a good screening programme?
1) The available test has high sensitivity and specificity
2) Test is not harmful
3) Defined pre-invasive stage which can be identified
4) Long enough to allow intervention
5) Simple, successful treatment
Is the cervical screening programme a test for cancer?
What testing does the cervical screening programme use?
Liquid based cytology and focused high risk HPV testing
What are the 4 main reasons for not screening people under 25?
1) Evidence doesn't support its use
2) High HPV carriage rate, including high risk types - 70-80% will be eliminated
3) Reactive changes produce confusing cytology
4) Unnecessary LLETZ procedures can have obstetric consequences
What is meant by dyskaryosis?
In the cervical screening programme what test is undertake if no dyskaryosis is found?
No further testing - normal recall
If low grade dyskaryosis is identified, what test is undertake?
HPV testing - if positive then refer for colposcopy and Rx
If negative then no further testing and normal recall
If high grade dyskaryosis is identified, what test is undertake?
Referred for colposcopy
What is the treatment for CIN?
LLETZ - Large Loop Excision of the Transformation Zone
What is the most important causative factor in the development of cervical squamous cell carcinoma?
What are the 7 other risk factors for cervical squamous cell carcinoma?
1) Multiple sexual partners
2) Male partner with multiple partners
3) Young age at first intercourse
4) High parity (lots of babies)
5) Low socioeconomic group
In addition to cervical squamous cell carcinoma, what other type of cervical cancer exists?
How does cervical squamous carcinoma present and spread?
The same as SCC
Is cervical adenocarcinoma related to HPV?
What is the precursor to cervical adenocarcinoma?
Cervical Glandular Intraepithelial neoplasia (CGIN)
How is cervical adenocarcinoma/ CGIN treated?
The same as CIN/SCC - LLETZ
Why is cervical adenocarcinoma thought to have a worse prognosis than cervical SCC?
Thought to be due to radioresistance
What staging system is used for cervical carcinoma, how many stages does it describe?
FIGO staging system - describes stages 1, 2, 3, 4