Cevical intraepithelial neoplasia

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CERVICAL INTRAEPITHELIAL NEOPLASIADr.WHITNEY JOSEPH CRRIDEPT OF OBGSMIMSCINCervical 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 1Undifferentiated cells are confined to the lower one-third of the epithelium Often due to infection in young wowen

MODERATE DYSPLASIA/CIN 2Undifferentiated cells occupy the lower 50-75% of epithelial thicknessThe cells are mostly intermediate with moderate nuclear enlargement , hyperchromasia , irregular chromatin and multiple nucleation.

SEVERE DYSPLASIA/CIN 3The entire thickness of epithelium is replaced by abnormal cells.


Can spontaneously regress to normalRemain stable for long periodOr progress to higher degree of dysplasiaNeoplastic potential increase with CIN grade

AETIOLOGYONCOGENIC FACTORS Malignant transformation of cell require the expression of E6 & E7 oncoproteins produced by HPV. the changes of HPV infection are decribed as KOILOCYTOSISHigh risk HPV 16,18,31,35,39,45,51,52,56 nd 58.95% of cervical cancer. Low risk HPV 6 and 11Cause genital warts.AKoilocyteis asquamous epithelialcell that has undergone a number of structural changes, which occur as a result of infection of thecellby HPV.


EthnicityLow socio economic statusIncreasing ageBEHAVIORAL RISK FACTORS Early coitarcheMultiple sexual partnersTobacco smokingDietary deficiencyMEDICAL RISK FACTORS

Exogenous hormonesParityImmuno suppressionInadequate screeningCERVIX AND TRANSFORMATION ZONE



HPV DNA detection (PCR, Southern Blot Assay, Hybrid Capture)SCREENING GUIDELINESINITIATION 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 LifePrior 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 TESTHave high specificity and lower sensitivity PATIENT PREPARATIONShould 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 DEVICESSpatula to predominantly sample ectocervixFirmly 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 epitheliumHave 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 COLLECTIONCONVENTIONAL SLIDE COLLECTIONSpatula is quickly spread as evenly as possible over 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 COLLECTIONImproved cell collection and preparation qualityProduce even monolayer of cells Random distribution of abnormal cells.


GENERAL CONSIDERATION Negative for intraepithelial lesion or malignancyEPITHELIAL CELL ABNORMALITYSQUAMOUS CELL ABNORMALITY Atypical squamous cellsASCUSASC-H Low grade intra epithelial lesionHigh grade intra epithelial lesionSquamous 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.

COLPOSCOPYCLINICAL INDICATION Grossly visible genital tract lesion Abnormal cervical cytologyHistory of in utero diethylslibutrol exposeUnexplained genital track bleeding CONTRAINDICATION upper and lower reproductive track infection.Uncontrolled severe hypertension.SOLUTION USED Normal salineSaline 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 neoplasmIt 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 LESIONCOLPOSCOPIC SIGN ZERO POINT ONE POINT TWO POINTMARGINCondylomatousMicropapillaryFeartherySatellite lesionSmoothstraightPolled PeelingInternal borderCOLOUR AND ACETOWHITINGShinnySnowyTransulucentTransientDuller whiteDull white grayVESSELSFine patternUniform caliberabsentCoarse patternVariable caliberVASCULAR PATTERN

PUNCTATIONMOSAICISMBIOPSYECTOCERVICAL BIOPSY under direct colposcopic visualization suspicious lesion on the ectocervix are biopsied using sharp instrument such as tischler biopsy forcepsThickened Monsel solution or silver nitrate appliedExtreme 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 canalThe entire length and circumference is firmly curetted carefully avoiding sampling of ectocervix or uterine cavity

MANAGEMENTTREATMENT OF PREINVASIVE LESIONLOCAL DESTRUCTION cauterizationCryosurgeryLaser ablationLOCAL EXCISION LEEPConisation with knife , laser RADICAL EXCISIONHysterectomyCIN 1 can be observed indefinitely, especially in adolesents. Rx is acceptable if it persist for atleast 2yrsCIN 2 observation in adolescent& young. excision or ablation in adult.CIN 3 Excision or abalation at any age.

ABLATION TREATMENT MODALITIESEffective for non invasive ecto cervical disease.Evidence of glandular or invasive carcinoma should be excluded.CryotherapyCarbondioxide laserElectro diathermyCRYOTHERAPY Principle is crystallizing intracellular water.Usually nitrous oxide is used.Ideal for ectocervical lesion associated with satisfactory colposcopyNot used for CIN 3

CO2 LASER ABALATION laser is delivered using colposcopic guidance with a micro manupulatorIs 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.

ADVANTAGEDISADVANTAGEFavorable safty profileNo tissue specimen for histopathological examinationOut patient procedureCannot treat lesion with unfavorable size or shapeNo anaesthetic requirmentsUterine crampingLow cost equipmentPotential for vasovagal reactionBleeding complication rareProfuse vaginal discharge, post procedureNo proven adverse reproductive effectCephalad migration of squamocolumar junctionEXCISION 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 tissueCan be used for high grade cervical lesion including those that extend into endocervical canal

ADVANTAGEDISADVANTAGEFavarable safty profileThermal damage may obsure specimen marginEase of procedureSpecial training requiredOut patient procedure using L.ARisk of post procedure bleedingTissue specimen for histopathological examinationPossible increased risk of adverse reproductive outcomesLow cost equpimentCOLD KNIFE CONIZATION surgical procedure to remove the cervical transformation zone including cevical lesionRequier 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 EXCISIONHYSTRECTOMY Prefered for older & parous women.When women cannot comply with follow up.If CIN lesion is associated with fibroid, DUB or prolapseIf microinvasion excits.Cancer phobia.


CERVARIX- bivalent vaccine against HPV 16,18GARDSIL - Quadravalent vaccine against HPV 6,11,16,18FIRST DOSE At elected time before exposure to sexual activity(0.5ml)SECOND DOSE 2 month after first injection.THIRD DOSE - 6 month after first injectionCONTRAINDICATION- pregnancySIDE EFFECTS- fever ,local pain & erythema.