Cervical and Vulval Pathology Flashcards
What is meant by CIN, CGIN, VIN, VaIN and AIN?
What do they all have in common?
CIN - cervical intraepithelial neoplasia
CGIN - cervical glandular intraepithelial neoplasia
VIN - vulval intraepithelial neoplasia
VaIN - vaginal intraepithelial neoplasia
AIN - anal intraepithelial neoplasia
These all have dysplasia and are caused by human papilloma viruses (HPV)
What is meant by dysplasia?
A neoplastic change in an epithelium, which is not invasive yet
What is meant by dysplasia?
How is it similar to malignancy?
How should it be treated?
It is the earliest morphological manifestation of the multistage process of neoplasia
it has the cytological features of malignancy, but no invasion (in-situ disease)
removal is curative as if it is left there is a significant chance of malignancy
How is the removal of dysplasic tissue related to the cervical screening programme?
Recognition of dysplasia gives the opportunity to treat a potentially fatal tumour before it arises
the abnormal cells have not yet acquired the capacity for invasion
elimination of the abnormal cells removes the basis on which cancer will develop
Why is it important to recognise dysplasia on a smear test?
The abnormal cells are identified from a smear test
it is important to try and capture and treat the abnormal cells before they reach the basement membrane and become invasive
How is intraepithelial neoplasia categorised?
It is classified into 3 stages depending on where the neoplastic cells are ascending in the epithelial thickness
CIN I , CIN II , CIN III
What are human papillomaviruses (HPV)?
How many subtypes are there and what tissues do they affect?
Double stranded DNA viruses
There are > 100 subtypes, based on DNA sequence
different types affect different tissues and not all subtypes are oncogenic
What are the 2 categories of genital HPVs?
What % of women will get HPV in their lifetime?
Genital HPVs can have low and high oncogenic risk
80% of women will contract HPV in their lifetime
In most women, HPV causes no long term harm and is cleared by the immune system
These are the low oncogenic risk strands that are not linked to cancer
What are the 2 main low risk HPVs?
What conditions are they associated with?
6 and 11
they are associated with genital warts and other low-grade cytological abnormalities (skin infections)
What are the 2 main high risk HPVs?
What are they associated with?
16 and 18
they are associated with high-risk pre-invasive and invasive disease
they are associated with 70% of all cervical cancers
What do low risk HPV 6 and 11 cause?
How is it transmitted?
- Lower genital tract warts called condylomata (benign squamous neoplasms)
- very rare in malignant lesions
genital warts are a sexually transmitted infection and can occur on the cervix, vagina, vulva, perineal skin and anus
What are the treatments for genital warts?
What are some of the associated risks?
They are unsightly and can be painful and cause bleeding
they can be transmitted to a baby during vaginal delivery
they are treated with topical creams / liquids, cryotherapy, or surgical ablation depending on size
What do the high risk HPV 16 and 18 tend to cause?
High grade intraepithelial neoplasia (CIN II and III) and invasive carcinomas
What are the 2 different HPV vaccinations and what do they cover?
Cervarix:
- covers high risk HPV 16 and 18
- UK vaccination began in 2008 using this on girls only
Gardasil:
- covers high risk HPV 16 and 18
- also covers low risk HPV 6 and 11
- began being used in 2012
What is the current HPV vaccination programme?
Both boys and girls are vaccinated
< 15 years - 2 doses given (0 and 6-12 months)
> 15 years. - 3 doses given (0, 2 and 4-8 months)
If missed, the vaccine can be given up to age 25 for free
Why was the HPV vaccination offered to boys?
- To increase herd immunity
- to decrease head and neck, anal and penile cancers
- to decrease incidence of genital warts
What is the difference between early genes and late genes in HPV mode of action?
Early genes:
- expressed at onset of infection
- control viral replication
Late genes:
- in oncogenic viruses, they are involved in cell transformation
- encode capsid proteins
What is meant by “open reading frames” in viral genomes?
Whar are the main molecular pathways (early ORFs) used by HPV?
E6:
- binds and inactivates p53
- this is a housekeeping gene protein that destroys cells that contain genetic mutations
- when inactivated, this stops apoptosis and allows damaged cells to proliferate
E7:
- binds to retinoblastoma protein (RB1)
- this is a tumour suppressor gene that controls cell proliferation
- inactivating it leads to dysregulation of cell proliferation
Accumulation of damaged cells which are neoplastic
How do high risk HPVs interact with the host genome?
High risk HPVs integrate into the host genome
this leads to upregulation of E6 and expression of E7
What is meant by the ‘transformation zone’ of the cervix?
how does it develop?
A physiological area of squamous metaplasia
Pre-puberty:
- the endocervical canal contains glandular crypts
- the external os is where the glandular epithelium changes to squamous
- the ectocervix is lined with squamous epithelium
Puberty:
- the endocervical canal extends out so the squamocolomnar junction is now below the external os
- there is a metaplastic change to squamous epithelium
Menopause:
- the squamocolumnar junction retracts back into the endocervical canal
What is significant about the transformation zone of the cervix?
It is vulnerable to the oncogenic effects of HPV
It is the site of development of CIN (intraepithelial neoplasia)
during a smear test, cells are sampled from this region
Why is it harder to perform a smear test after menopause?
The squamocolumnar junction (transformation zone) has retracted back into the endocervical canal
it is more difficult and invasive to obtain a sample from the transformation zone
What are the different cell types present in the endocervix, ectocervix and endocervical canal?
Endocervix:
- soft, columnar glandular cells
Ectocervix:
- hard, squamous cells
Endocervical canal:
- transition zone where glandular cells transform into squamous cells
What types of conditions originate from glandular and squamous cells in the cervix?
Glandular:
- CGIN
- adenocarcinoma
Squamous:
- CIN
- squamous cell carcinoma
What is the aim of the cervical screening programme?
Detection of cervical intraepithelial neoplasia (CIN)
CIN is graded according to increasing abnormality
this shows the correlation between the cytology of cells brushed off the surface of the epithelium, with the underlying dysplasia changes in the epithelium
What is the frequency of cervical screening in different age groups?
25 - first invitation
25-49 - every 3 years
50-64 - every 5 years
65+ only those not screened since age 50 or if recent abnormal tests
What can cervical intraepithelial neoplasia lead to?
It is the pre-invasive stage of cervical squamous cell carcinoma
How is the cervical screening programme performed NOW?
Liquid based cytology has been phased out in favour of high risk HPV testing
the HPV primary triage is the current method used when looking at smear tests
What are the 4 stages in the simplified FIGO staging for cervical carcinoma?
I - confined to cervix
II - invades beyond uterus, not to pelvic side wall
III - extends to pelvic wall, lower 1/3 vagina, hydronephrosis
IV - invades bladder or rectum or outside pelvis
palliative care may be an option in III and IV with a poor 5 year survival
What is the risk of lymph node metastases in vulval squamous cell carcinoma?
How is it treated?
If depth of invasion is <1mm, lymph node metastases are rare and wide local excision is performed
if depth of invasion is > 1 mm then lymph node sampling is performed
How do gynaecological cancers tend to be staged?
What is the 5 year survival like for vulval squamous cell carcinoma?
Staged using the FIGO system
the later stages have poor prognosis
overall prognosis is 70%
