46 - Diseases of the female genital system Flashcards
VIN stands for
Vulval intraepithelial neoplasia
CIN stands for
Cervical intraepithelial neoplasia
CGIN stands for
Cervical glandular intraepithelial neoplasia
VaIN stands for
Vaginal intraepithelial neoplasia
AIN stands for
Anal intraepithelial neoplasia
HPV virus - genetics and lifecycle
Double stranded DNA virus
Circular genome - 7 early genes, 2 late genes
> 100 subtypes
Different types over different tissues
Genital HPVs grouped into low and high oncogenic risk
Low risk HPV numbers
6, 11 - linked with genital warts are most common
High risk HPV numbers
Associated with high grade pre-invasive and invasive disease: 16, 18
Low risk HPV 6,11
Lower genital tract warts
Low grade intraepithelial neoplasias which rarely form lesions
High risk HPV 16, 18
High grade ‘IN’s and invasive carcinomas
Low risk vaccine called
Gardasil
High risk vaccine called
Cervarix
High risk HPV - mode of action
Integrates into host chromosomes
Upregulates E6, E7 expression which inactivates p53 and binds to RB1 gene product
What does p53 do?
Mediates apoptosis in response to DNA damage which leads to accumulation of genetic damage
What does RB1 do?
Tumour suppression gene controls G1/S checkpoint in cell cycle
== dysregulation of cell proliferation
How are VINs stained?
Toluidine blue
Vulval intraepithelial neoplasia - histology
Classical / warty / baseloid:
Graded VIN 1-3
Related to HPV
In young people
Differentiated: Not graded Not HPV related Occurs in chronic dermatoses Older people
Behaviour of VIN
50% recur
Progression to invasive carcinoma is 4-7% in treated women and 87% in untreated
Most common vulval cancer is
Squamous cell (90%)
Squamous cell carcinoma in
Associated with VIN
Squamous cell carcinoma in >70
Inflammatory dermatoses in age>70
Due to lichen sclerosus and lichen planus
Lymph nodes mets rely on what in vulval squamous cell carcinomas
Depth
4mm = 40%
Malignant melanoma of the vulva
5% of vulval cancers Mean age 50-60 Local recurrence in 1/3 Spreads to urethra Lymph node/haematogenous spread common Depth of invasion correlates with lymph node involvement
Other vulval tumours
Paget’s disease
Paget’s disease
Usually no underlying tumour
5% regional malignant disease - bladder, cervix, rectal
What happens to the external os in a post menopausal state?
Transitional zone retracts up the canal and pulls up external os
What do cervical screening programmes aim to find?
Cervical intraepithelial neoplasia
To find pre-invasive stage of cervical squamous cell carcinoma
How many CIN types are there?
3
Which CIN type is most likely to become invasive?
CIN 3
What do you do if low grade dyskaryosis is found on screening?
HPV screening, if positive, refer to colposcopy + Rx
-ve = normal recall
What is you have high grade dyskaryosis found on screening?
Refer to colposcopy + Rx
What is colposcopy?
Examination of cervix with low powered stereoscopic microscope
What does LLETZ stand for?
Large loop excision of the TZ
What stain is used in colposcopy?
Acetic acid which highlights abnormal epithelium
Risk factors for cervical squamous cell carcinoma
High risk HPV is most causative Multiple sexual partners Male partner with multiple partners Young age at first intercourse High parity Low socioeco Smoking Immunosuppression
