Download Premalignat disease of the cervix

PREMALIGNAT DISEASE
OF THE CERVIX
 Cervical cancer kills about 250000 women a year.
 It’s the commonest cause of death from cancer
in women .it’s the commonest after breast
cancer.
 80% of cases are reported in developing
countries.
 In developed countries regular screening
program has reduced the incidence of cervical
cancer.
 Cervical cancer is a preventable disease




because of:
1. There is usually a phase of premalignant
intra-epitheilial neoplasia with long natural
history.
2. The cervix is a relatively accessible organ
to examine.
3. simple test available for the diagnosis of
the presence of pre-malignancy.
4. Treatment for pre-invasive disease is
highly effective.
Premalignant disease
of the cervix
 1.cervical disease
 2.Cervical intraepithelial neoplasia
 (Cervical dysplasia)
Aetiology
 Human papillomavirus (HPV) infection.
There are 15 high risk type of HPV,type 16-18
is responsible for 70% of cases.type 6 and
11 is associated with cervical condylomata




and low grwde CIN.
HPV infection is extremely common and in
majority of cases will not lead to
development of cancer. Progression or
regression depends on several factors that
interfere with the host's ability to clear the
virus such as in.
Transplant patient.
HIV-Positive women.
Smoking.
 Adolescent cervix is more susceptible to
carcinogenic stimuli because of active process
of squamous metaplasia which occur within the
transformation zone.
 Squamous metaplasia is an physiological
process but under the influence of HPV ,cellular
alterations occurs that resultatypical
transformation zone initiate CIN.
Screening for cervical
intraepithelial neoplasia (CIN)
 Medical screening method
 Detect premalignant and malignant processes of
cervix.
 Prevent progression of abnormal cells to cancer.
 This is NOT a diagnostic test!
 Cervical cancer screening with cytology
provides the opportunity for early effective
intervention and has reduced morbidity
and mortality
 Papanicolaou
 Cervicoscopey
 Visual inspection with acetic acid (VIA)
 Visual inspection with acetic acid and
magnification (VIAM).
 Colposcopy
 Cervicography
 Automated pap smears
 Molecular (HPV/DNA) tests.
 Co-testing using the combination of cytology
plus HPV DNA testing is an appropriate
screening test for women older than 30 years
(applied in some places).
Papanicolaou (Pap) smear test
Is a screening test for asymptomatic Women
to detect treatable pre-invasive squamous
abnormalities of the Cervix
 Small number of women will develop invasive
Cancer
 Not diagnostic-rather screening test to detect
early changes on the cervix.
 Exfoliative cervical cytology was a technique to




collect the cells that had been shed from the
cervix.
It is a simple and painless test that may cause
minor discomfort.
Cervical Smear aims to prevent cancer, not to
detect cancer.
Cervical cancer screening should begin at age 21
years and not before age 21 because it may lead to
unnecessary and harmful evaluation and
treatment in women at very low risk of cancer.
Women who have been immunized against HPV16 and HPV-18 should be screened by the same
regimen as nonimmunized womenbecause it
doesn’t prevent against all high –risk HPV viral
type.
frequency of cervical cytology
screening
 Annual cervical cytology screening is
recommended for women aged 21–29 years.
 Women aged 30 years and older who have had
three consecutive cervical cytology
 test results that are negative for intraepithelial
lesions and malignancy may be screened every
2-3 years.
 *women with any of the following risk factors
may still require more frequent cervical cytology
screening:
• Women who are infected with human
immunodeficiency virus (HIV)
• Women who are immunosuppressed (such as
those who have renal transplants).
• Women who were exposed to diethylstilbestrol in
utero.
• Women previously treated for CIN 2, CIN 3, or
cancer (continue to have annual screening for at
least 20 years).
Pap Smear is not necessary in women in these
categories:
 Virgin patient.
 Total Hysterectomy for benign disease.
 Recent result of pap smear.
 Age over 65 and over 10 benign Pap Smears.
Preparation
 To prepare for the Pap test, for two days
before the test ,women should avoid:
 Vaginal Douching .
 Using tampons.
 sexual intercourse.
 Using birth control foams, creams, or jellies or
vaginal medications or creams.
 the ideal time for a woman to have a Pap
Smear is five days after her menstrual
period has ended.
 Exfoliated cells are collected from the
transformation zone of the cervix by Use
spatula of different size or brush.
 There are two methods of preparing and
processing cervical smear slides.
 These methods are:
1. conventional cervical (Pap) smear test.
collecting the cells smears on a microscope
slide and applies a fixative. The slide is sent to a
laboratory for evaluation.
•The Spatula with the optimal shape and size is chosen .
Broom type sampler
 The 'tongue' of the spatula is introduced into
the canal, whilst its 'shoulder' is positioned
on the 3 o'clock position of the ectocervix at
the beginning of the procedure . With gentle
pressure the spatula is rotated in a clockwise
direction.
 2. liquid based cytology (LBC) test.
 Cell transferred to a vial of liquid
preservative that is processed in the
laboratory to produce a slide for
interpretation by light microscopy.
Classification of CIN
 A. CIN classification
 CIN 1 (mild dysplasia) involvement of the
inner one-third of the epithelium.
 CIN 2 (moderate dysplasia) involvement of
inner one-half to two-third
 CIN 3 (severe dysplasia/carcinoma in situ)
full thickness involvement.
Figure 17.1 Diagram of cervical intraepithelial neoplasia
compared with normal epithelium.
 Or can be classified as:
 *Low grade lesions (CIN1 and HPVassociated changes) in which there is a
significant chance of regression and low
progressive potential.
 *High grade lesions (CIN 2 and CIN 3) are
likely to behave as cancer precursors.

A: Active metaplasia in the transformation
zone. B: Maturing metaplasia in the
transformation zone.
 A diagnosis of CIN is based primarily on the presence of




nuclear a typia and loss of normal squamous maturation
(polarity).
Accurate grading of CIN lesions becomes important as we
begin to understand the rates of regression, persistence and
progression of the low-grade (CIN 1) and high-grade lesions
(CIN 2 and 3), as their treatment and clinical follow-up are
quite different.
Cervical pre-cancer has along natural history.
36% of women with CIN3 would develop invasive cancer if left
untreated.
More than 40% of women with minor cytological
abnormalities will revert to normal without treatment.
Clinical presentation
 The disease is a symptomatic. The
premalignant lesions cause no symptoms and
are not recognizable with the naked eye.
Results of the cervical smear
test
 The cytologist will classify the smear accordingly:
 Normal results:
 Mean that no atypical, dysplastic, or cancer cells
were detected, and the cervix is normal. It is seen
in About 9 in 10 routine cervical screening tests.
 (Note: a normal result means a very low chance of
developing cancer of the cervix - not a 100%
guarantee that it will not occur.)
 Abnormal result:
 Some changes in the cells are found in
about 1 in 10 tests. There is a range of
changes that may occur. In nearly all cases,
these changes do not mean cancer.
Inflammatory –excessive leucocytes,
candida or trichomonas.
 Borderline.( Cellular appearance that




cannot be described as normal).
Mild dysplasia
Moderate dysplasia.
Severe dysplasia.
Possible invasive carcinoma. Rarely, a
cancer of the cervix is diagnosed by a
cervical screening test.
Management of abnormal cervical
smears
 Inflammatory smears should be treated by
antibiotics or antifungal agents accordingly.
And the smear repeated 3-6 months later.
 Border line smear advice to Repeat smear
in 6-12 months and refer for colposcopy if
abnormalities persist.
 Ideally all women with abnormal cervical
cytology(some mild ,moderate ,sever
dysplasia) should have colposcopic
assessment to exclude an invasive process
and to identify the extent of abnormality.
Colposcope
 Minor or borderline abnormal changes are quite
common. These often clear away on their own
and most mild changes do not progress to
anything serious. However, any change needs to
be monitored as some may progress to become
more serious in the future. A repeat test after 312 months is commonly advised, depending on
the type and degree of change. Often the
changes will be resolved when the test is
repeated. If the changes don’t resolved or the
changes are more marked, then a referral to
colposcopy is advised.
 Any patient with a grossly abnormal cervix
should have a punch biobsy regardless of
the results of Papanicolaou smear.
Inflammation
CIN1
CIN2
CIN3
CIN3 ca in situ
Squamous cell carcinoma
CIN2
High Grade SIL
CIN1
Low grade SIL (L-SIL)
The cytologic features of normal squamous epithelial cells can be seen
at the center top and bottom, with orange to pale blue plate-like
squamous cells that have small pyknotic nuclei. The dysplastic cells in
the center extending to upper right are smaller overall with darker,
more irregular nuclei.
Gardnerella Vaginalis
Mixed bacterial flora
Candida
HERPS
Colposcopy:
 It is a binocular operating microscope with
 magnification of 5-20 times. Indicated for further





investigation of smear abnormalities.
It has been used to examine the cervix in detail to:
*Identify dysplastic abnormalities on the ectocervix.
*Detect changes in the cellular pattern and vascularity
of the covering epithelium.
*Allow the accurate localization of the abnormal
epithelium.
*Exclude an invasive process.
Colposcopic examination
We have two methods:
1.Saline method.The cervix and vagina is moistened
thoroughly with normal saline in order to view the
vascular pattern. Gross lesion, vascular details and
opacity of epithelium is noticed.
Green filter is used to evaluate the details of vascular
epithelium when the blood vessels appears dark.
Occasionally abnormal epithelium will stand out from
The surrounding epithelium.
 CIN has the potential to be an invasive
malignancy but dose not have malignant
properties. High grade lesions (CIN2 and
CIN3) should be treated, but there is some
debate about CIN1 they allow CIN 1 lesions
to be treated or kept under close
surveillance.
Classical or extended method:
 Acetic acid test :After removing the excess mucos ,
the cervix is liberally moist with a large swab of
loose cotton wool soaked in dilute acetic acid of 35%,by this all the epithelia with high nucleocytoplasmic ratio will turn white. this action is
transient and disappear after 1-3 minutes, and it’s
better to wait for at least a minute before recording
the acetowhite changes .
Satisfactory colposcopy :The important part of
colposcopy is to look for the entire sequaocoluminar
junction and one should be able to see the overlying
columinar epithelium even if it’s inside the cervical
canal then to examine the vaginal fornices and
walls.
 Tissues with high nuclear activity and high
nuclear-cytoplasmic ratio turn white after
application of acetic acid, the faster the aceto
whiteness appears and the longer it persist
will reflect the degree of underlying
abnormality and more likely to be high grade
intraepithelial lesion
Acetic acid test
Acetic acid test
 Iodine test:
The cervix and vagina is liberally painted with iodine
solution with 50% aqueous solution because alcohol
cause destruction of epithelium.brown staining will
occur in glycogen rich epithelium(sequamous
epithelium).
Iodine negative areas occurs in :
 Inflammation
 Columnar epithelium.
 Thin regenerating epithelium.
 Immature metaplasia.
 Atrophic epithelium
 HSIL
Normal colposcopic finding
 Original sequamous epithelium.
Pink smooth featureless on the cervix and vagina no
Remnants of columnar epithelium such as gland
Opening Or nabothian cysts . it doesn’t turn white
after acetic acid applications and stain brown after
application of lugol’s Iodine.
Sometimes vascular pattern as looped capillaries
or as fine net work .
Treatment of CIN

The treatment for cervical dysplasia must be
individualized for each woman, taking into account:
1. the grade of the dysplasia (CIN1, CIN2, or CIN3).
2. the findings at colposcopy.
3. the woman's age.
4. reproductive status.
5. and other factors.
Treatment for CIN include:
 CIN has the potential to be an invasive
malignancy but dose not have malignant
properties. high grade lesions (CIN2 and
CIN3) should be treated, but there is some
debate about CIN1 as some allow CIN 1
lesions to be treated and others advice to
be kept under close surveillance..
 Treatment involves completely removing the abnormal









epithelium.
This can be done by:
1. Destroying the abnormal epithelium.( cryosurgery,
laser vaporization)
2. Excisional techniques:(This allows better
histopathological interpretation of the excised specimen).
These techniques include:
a. local excision
b. loop electrode excision procedure (LEEP).
c. cone biopsy.
d. trachelectomy (excision of cervix).
e. hysterectomy.
 The success of treatment is usually defined
as negative cytology 6 months following
intervention.
 Therapeutic vaccination aims to boost
host's cell-mediated immunity but still
experimental.
 Follow up:
 Follow up of patient treated for CIN is
controversial between colposcopy or
cytology. other tests such as a HPV DNA
test may be advocated
 LEEP (loop electrosurgical excision procedure(.
After freezing the area with local anesthetic, an
electrical wire loop is inserted into the vagina and all
the abnormal tissue is removed. This procedure is
also done in the physician's office.
 A cone biopsy
refers to removal of a cone-shaped piece of tissue.
The tissue removed provides a more extensive
sample for diagnosis than a simple biopsy. A cone
biopsy is usually done in the operating room.
 The cold cone biopsy is a surgical procedure requiring
general anesthesia and is indicated by the presence of
precancerous changes in the cervix .
What happens after treatment?
 After treatment for dysplasia, patients are
followed closely to make sure all the dysplasia is
gone, and that new dysplasia does not
occur. Typically, patients are followed with
frequent Pap smears for two years after
treatment, e.g. Pap smears every 3 to 4 months
for the first year, and then every 6 months for
the second year. If all the Pap smears come back
negative, the patient is be cured, and is then
followed with yearly Pap smears.
 A colposcopy-directed biopsy is a procedure in which
the cervix is examined with a colposcope for
abnormalities and a tissue sample is taken .
Thank you