Dr.WHITNEY JOSEPH
CRRI
DEPT OF OBG
SMIMS
CIN Cervical intraepithelial neoplasia refers to the
histopathological description in which a part or the full thickness of stratified squamus epithelium is replaced by cell showing dysplasia.
MILD DYSPLASIA/ CIN 1
Undifferentiated cells are confined to the lower one-third of the epithelium
Often due to infection in young wowen
MODERATE DYSPLASIA/CIN 2
Undifferentiated cells occupy the lower 50-75% of epithelial thickness
The cells are mostly intermediate with moderate nuclear enlargement , hyperchromasia , irregular chromatin and multiple nucleation.
SEVERE DYSPLASIA/CIN 3
The entire thickness of epithelium is replaced by abnormal cells.
NATURAL HISTORY
Can spontaneously regress to normal
Remain stable for long period
Or progress to higher degree of dysplasia
Neoplastic potential increase with CIN grade
AETIOLOGY ONCOGENIC FACTORS
Malignant transformation of cell require the expression of E6 & E7 oncoproteins produced by HPV.
the changes of HPV infection are decribed as KOILOCYTOSIS
High risk HPV
16,18,31,35,39,45,51,52,56 nd 58.
95% of cervical cancer.
Low risk HPV
6 and 11
Cause genital warts.
A Koilocyte is a squamous epithelial cell that has undergone a number of structural changes, which occur as a result of
infection of the cell by HPV.
RISK FACTORSDEMOGRAPHIC RISK FACTORS
Ethnicity
Low socio economic status
Increasing age
BEHAVIORAL RISK FACTORS
Early coitarche
Multiple sexual partners
Tobacco smoking
Dietary deficiency
MEDICAL RISK FACTORS
Exogenous hormones
Parity
Immuno suppression
Inadequate screening
CERVIX AND TRANSFORMATION ZONE
SCREENING1. PAP Test
2.Colposcopy
3.HPV – DNA detection(PCR, Southern Blot Assay,
Hybrid Capture)
SCREENING GUIDELINES INITIATION OF SCREENING
Screening begins at the age of 21 yrs regardless of sexual history.
Or 3 yrs after the first sex. SCREENING INTERVEL
B/W age of 21 & 29 – Pap testing at 2 yrs interval After 30 yrs – 3 yr interval, if three previous
consecutive pap test have been documented as negative.
For HIV infected women – Annual screening for Life Prior Rx for CIN 2,3 – Atleast for 20 years
DISCONTINUATION OF SCREENING May be stopped at age 65 or 70, after three
consecutive negative pap resulting during the prior 10 years.
PAP TEST Have high specificity and lower sensitivity
PATIENT PREPARATION
Should be scheduled to avoid menstruation
Should abstain from vaginal intercourse,use of vaginal tampons and contraceptive creams should be avoided for minimum of 24 or 48 hrs before the test.
Provision of clinical information on requisition form
SAMPLING DEVICES Spatula
to predominantly sample ectocervix
Firmly scrapes the cervical surface, completing at least one full rotation
Endocervical brush
to sample endocervical canal.
Endocervical brush is inserted into the endocervical canal only until the outermost bristles remain visible.
The brush is rotated only one quarter to one- half turn.
BROOM
to sample both endo and ecto cervical epithelium
Have longer central bristles that are inserted into the endocervix,these longer bristles are flanked by shorter bristles that splay out over the ectocervix during rotation.
Usually five rotation in same direction
SPECIMEN COLLECTION CONVENTIONAL SLIDE COLLECTION
Spatula is quickly spread as evenly as possible over ½ to 2/3 of glass slide.
The endocervical brush is firmly rolled over the remaining area of the slide
Fixation is carried out by spraying or immersing in fixative.
LIQUID BASED TEST COLLECTION
Improved cell collection and preparation quality
Produce even monolayer of cells
Random distribution of abnormal cells.
2001 BETHESDA SYSTEM
GENERAL CONSIDERATION Negative for intraepithelial lesion or malignancy
EPITHELIAL CELL ABNORMALITY SQUAMOUS CELL ABNORMALITY
Atypical squamous cells
• ASCUS
• ASC-H
Low grade intra epithelial lesion
High grade intra epithelial lesion
Squamous cell carcinoma
HPV DNA DETECTION PCR, Southern Blot Assay, Hybrid Capture
HPV testing alone twice as sensitive as pap test but lacks specificity.
Hybrid capture 2 test for HR-HPV in combination with cytology for primary cervical screening in women aged 30yrs & older.
Cotesting increases the sensitivity of single PAP testing for high grade neoplasia for 85% to 100%
If cytology is negative and HPV testing is positive, Cytology and HPV DNA testing are repeated 1yr later.
Persistent positive HPV DNA testing needs colposcopy.
COLPOSCOPY CLINICAL INDICATION
Grossly visible genital tract lesion
Abnormal cervical cytology
History of in utero diethylslibutrol expose
Unexplained genital track bleeding
• CONTRAINDICATION upper and lower reproductive track infection.
Uncontrolled severe hypertension.
SOLUTION USED
Normal saline Saline remove cervical muscus and allows initial assessment
of vascular pattern and surface contours.
Acetic acid
Applying acetic acid to abnormal epithelium result in the aceto white change characteristic of neoplasm
It exerts its effect by reversibly clamping nuclear chromatin.
3-5% is a mucolytic agent.
LUGOL SOLUTION
stains mature squamous epithelial cells a dark brown colour as a result of high glycogen content.
Due to poor cell differentiation, dysplastic cells have lower glycogen level, fails to fully stain
COLPOSCOPIC GRADING OF LESIONCOLPOSCOPICSIGN
ZERO POINT ONE POINT TWO POINT
MARGIN CondylomatousMicropapillaryFeartherySatellite lesion
Smoothstraight
Polled PeelingInternal border
COLOUR AND ACETOWHITING
ShinnySnowyTransulucentTransient
Duller white Dull white gray
VESSELS Fine patternUniform caliber
absent Coarse patternVariable caliber
VASCULAR PATTERNPUNCTATION MOSAICISM
BIOPSY ECTOCERVICAL BIOPSY
under direct colposcopic visualization suspicious lesion on the ectocervix are biopsied using sharp instrument such as tischler biopsy forceps
Thickened Monsel solution or silver nitrate applied
Extreme case of bleeding can be controlled with direct pressure or vaginal packing.
ENDOCERVICAL SAMPLING Endocervical curettage is performed by introducing an
endocervical curette 1 to 2 cm into cervical canal
The entire length and circumference is firmly curetted carefully avoiding sampling of ectocervix or uterine cavity
MANAGEMENT TREATMENT OF PREINVASIVE LESION
LOCAL DESTRUCTION
cauterization
Cryosurgery
Laser ablation
• LOCAL EXCISION
LEEP
Conisation with knife , laser
• RADICAL EXCISION
Hysterectomy
CIN 1 can be observed indefinitely, especially in adolesents.
Rx is acceptable if it persist for atleast 2yrs
CIN 2 observation in adolescent& young.
excision or ablation in adult.
CIN 3 Excision or abalation at any age.
ABLATION TREATMENT MODALITIES Effective for non invasive ecto cervical disease.
Evidence of glandular or invasive carcinoma should be excluded.
Cryotherapy
Carbondioxide laser
Electro diathermy
CRYOTHERAPY
Principle is crystallizing intracellular water.
Usually nitrous oxide is used.
Ideal for ectocervical lesion associated with satisfactory colposcopy
Not used for CIN 3
CO2 LASER ABALATION
laser is delivered using colposcopic guidance with a micro manupulator
Is used to vaporize tissue to a depth of 5-7mm.
Ideal for biopsy proven SIL associated with satisfactory colposcopy,condylomatous and dysplastic lesion.
ELECTRO DIATHERMY
Uses unipolar electrode
8-10 mm depth can be destroyed.
ADVANTAGE DISADVANTAGE
Favorable safty profile No tissue specimen forhistopathological examination
Out patient procedure Cannot treat lesion with unfavorable size or shape
No anaesthetic requirments Uterine cramping
Low cost equipment Potential for vasovagal reaction
Bleeding complication rare Profuse vaginal discharge,post procedure
No proven adverse reproductive effect
Cephalad migration of squamocolumar junction
EXCISION TREATMENT MODALITIES
indicated for unsatisfactory colposcopy with histological CIN, recurrent AGC cytology.
MODALITIES LEEP
Cold knife conization.
Laser conization.
LEEP(Loop Electro surgical Excision Procedure) simultaneously cuts and coagulate the tissue
Can be used for high grade cervical lesion including those that extend into endocervical canal
ADVANTAGE DISADVANTAGE
Favarable safty profile Thermal damage may obsure specimen margin
Ease of procedure Special training required
Out patient procedure using L.A
Risk of post procedure bleeding
Tissue specimen for histopathological examination
Possible increased risk of adverse reproductive outcomes
Low cost equpiment
COLD KNIFE CONIZATION surgical procedure to remove the cervical transformation zone
including cevical lesion
Requier G.A or reginal anaesthesia.
Prefered for high grade CIN extending deep into the endocervical canal, for endocervical glandular disease.
Patient selection, Ideal for patient older than 35yrs with CIN3 & CIS and patient with risk of invasive cancer.
RADICAL EXCISION HYSTRECTOMY
Prefered for older & parous women.
When women cannot comply with follow up.
If CIN lesion is associated with fibroid, DUB or prolapse
If microinvasion excits.
Cancer phobia.
PROPHYLAXIS
CERVARIX- bivalent vaccine against HPV 16,18
GARDSIL - Quadravalent vaccine against HPV 6,11,16,18
FIRST DOSE – At elected time before exposure to sexual activity(0.5ml)
SECOND DOSE – 2 month after first injection.
THIRD DOSE - 6 month after first injection
CONTRAINDICATION- pregnancy
SIDE EFFECTS- fever ,local pain & erythema.
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