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.