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 regression, persistence and progression of CIN I like?
- Regression 60%
- persistence 30%
- progression to CIN III - 10%
- progression to invasion - 1%
Most cases of CIN I are caused by low risk HPV and will regress
90% will not change or get worse
What is the regression, persistence and progression of CIN II like?
- Regression - 40%
- persistence - 40%
- progression to CIN III - 20%
- progression to invasion - 5%
What is the regression, persistence and progression to invasion of CIN III like?
- Regression - 33%
- persistence - 56%
- progression to invasion - 20-70%
most cervical cancers are seen in women who do not go for smear tests and do not get their CIN III treated
What are the criteria for a cervical screening programme?
- High sensitivity and high specificity
- test is not harmful
- test is not too expensive
- test is acceptable to population
- defined pre-invasive stgae
- long enough to allow intervention
- simple, successful treatment available
What is meant by the cervical screening programme having high sensitivity and specificity?
High sensitivity:
- the test produces few false negatives
High specificity:
- the test produces few false positives
- it is specific to the condition that is being looked for
How could regular attendance for cervical screening affect prevalence of cancer?
The screening programme is NOT a test for cancer
it could prevent 90% of cancers
the rate of cervical cancer would be 50% higher without screening
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
Why are women below 25 years old not screened?
There is no supportive evidence base
there may be a high HPV carriage rate (including high risk types) but 70-80% will be cleared
reactive changes produce confusing cytology
unnecessary LLETZ procedures can have obstetric consequences
What can cervical intraepithelial neoplasia lead to?
It is the pre-invasive stage of cervical squamous cell carcinoma
What is meant by dyskariosis?
Having an abnormal nucleus
it refers to the abnormal epithelial cell which may be found in a cervical sample
as CIN progresses, the nuclei become blacker and the cytoplasm diminishes
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 is a colposcopy and how is it performed?
Examination of the cervical with a low powered stereoscopic microscope
the cervix is painted with acetic acid to highlight potentially abnormal epithelium, which can be resected under local anaesthetic with a diathermy loop
What is the treatment for CIN following colposcopy?
Large loop excision of the transformation zone (LLETZ)
What is the most important causative factor for cervical squamous cell carcinoma?
High risk HPV
What are other risk factors for cervical squamous cell carcinoma?
- Multiple sexual partners
- male partner with multiple partners
- young age at first intercourse
- high parity
- low socioeconomic group
-
SMOKING
immunosuppression
What are the typical clinical presentations of cervical squamous cell carcinoma?
The cervix is ulcerated so the lesion will often bleed or cause a discharge
if the tumour presents late, there may be signs and symptoms due to local spread
e.g. Spreading into the bladder / ureters and causing hydronephrosis and urinary symptoms
What is the presentation of cervical adenocarcinoma like?
What is the precursor?
The presentation / spread is the same as SCC
it is related to high risk HPV
the precursor is cervical glandular intraepithelial neoplasia (CGIN)
What is the difference in the prognosis of cervical adenocarcinoma and SCC?
Stage to stage it has a worse prognosis
it is treated the same as CIN/SCC but occasionally more aggressive treatment is given
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 typical metastasis pattern of cervical carcinoma?
It tends to spread to the pelvic and para-aortic lymph nodes
or it may spread via the blood to the lungs, bones, etc.
What are the 2 different types of vulval intraepithelial neoplasia (VIN)?
- Classical / warty / basaloid
- Differentiated VIN
What are the characteristics of classical VIN?
- It is graded VIN I - III
- it is related to HPV infection
- if affects younger women
What are the characteristics of differentiated VIN?
- Not graded
- not related to HPV
- tends to affect older women
- occurs in chronic dermatoses, especially lichen sclerosus
What % of VINs will recur?
What tends to predict recurrence?
35 - 50% recur
positive margins predict recurrence
What is the progression rate to invasive carcinoma like in VIN?
What factors make it more likely?
Progression to invasive carcinoma occurs in 4-7% of treated women
and
up to 87% of those left untreated
invasion is more likely to occur in postmenopausal women and immunocompromised
spontaenous regression may occur particularly in young, postpartum women
What is vulval squamous cell carcinoma associated with?
Associated with VIN:
- women <60
- associated lower genital tract neoplasia (CIN) and high risk HPV subtypes
Associated with inflammatory dermatoses:
- women > 70
- lichen sclerosus and lichen planus
- symptomatic lichen sclerosus has a 15% risk of malignancy
What does vulval squamous cell carcinoma look like?
Where does it tend to spread to?
It appears as an eroded plaque or ulcer that may bleed
it spreads locally to involve:
- vagina and distal urethra
- ipsilateral inguinal lymph nodes
- contralateral inguinal lymph nodes and deep iliofemoral lymph nodes
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%
What is Paget’s disease?
What does it look like and what can it develop into?
It is a pruritic, burning, eczematous patch
it is an in situ adenocarcinoma of the squamous mucosa
it often recurs following excision and can develop into an invasive adenocarcinoma
there is usually no underlying tumour as it is an extramammary disease
What is a malignant melanoma of the vulva?
Who does it tend to affect and where does it spread to?
Mean age 50-60 years
local recurrence in 1/3 and spreads to the urethra frequently
also spreads via lymph nodes and haematogenous spread
the depth of invasion correlates with lymph node involvement
What would a malignant melanoma look like?
It is heavily pigmented
