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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 FACTORS
 DEMOGRAPHIC 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
SCREENING
1.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 LESION
COLPOSCOPIC
SIGN
ZERO POINT ONE POINT TWO POINT
MARGIN Condylomatous
Micropapillary
Fearthery
Satellite lesion
Smooth
straight
Polled
Peeling
Internal border
COLOUR AND
ACETOWHITING
Shinny
Snowy
Transulucent
Transient
Duller white Dull white gray
VESSELS Fine pattern
Uniform caliber
absent Coarse pattern
Variable caliber
VASCULAR PATTERN
PUNCTATION 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 for
histopathological
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.
Cevical intraepithelial neoplasia

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Cevical intraepithelial neoplasia

  • 2. 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
  • 3.  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.
  • 4.
  • 5.
  • 6. 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
  • 7. 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.
  • 8. 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.
  • 9. RISK FACTORS  DEMOGRAPHIC RISK FACTORS Ethnicity Low socio economic status Increasing age
  • 10.  BEHAVIORAL RISK FACTORS  Early coitarche  Multiple sexual partners  Tobacco smoking  Dietary deficiency
  • 11.  MEDICAL RISK FACTORS  Exogenous hormones  Parity  Immuno suppression  Inadequate screening
  • 13.
  • 14. SCREENING 1.PAP Test 2.Colposcopy 3.HPV – DNA detection (PCR, Southern Blot Assay, Hybrid Capture)
  • 15. 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.
  • 16. 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
  • 17.  SAMPLING DEVICES  Spatula  to predominantly sample ectocervix  Firmly scrapes the cervical surface, completing at least one full rotation
  • 18.  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.
  • 19.  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
  • 20.  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.
  • 21.  LIQUID BASED TEST COLLECTION  Improved cell collection and preparation quality  Produce even monolayer of cells  Random distribution of abnormal cells.
  • 23.  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
  • 24. 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.
  • 25. 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.
  • 26.  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.
  • 27.  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
  • 28. COLPOSCOPIC GRADING OF LESION COLPOSCOPIC SIGN ZERO POINT ONE POINT TWO POINT MARGIN Condylomatous Micropapillary Fearthery Satellite lesion Smooth straight Polled Peeling Internal border COLOUR AND ACETOWHITING Shinny Snowy Transulucent Transient Duller white Dull white gray VESSELS Fine pattern Uniform caliber absent Coarse pattern Variable caliber
  • 30. 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.
  • 31.  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
  • 32. MANAGEMENT  TREATMENT OF PREINVASIVE LESION  LOCAL DESTRUCTION  cauterization Cryosurgery Laser ablation • LOCAL EXCISION  LEEP Conisation with knife , laser • RADICAL EXCISION Hysterectomy
  • 33.  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.
  • 34. ABLATION TREATMENT MODALITIES  Effective for non invasive ecto cervical disease.  Evidence of glandular or invasive carcinoma should be excluded.  Cryotherapy  Carbondioxide laser  Electro diathermy
  • 35.  CRYOTHERAPY  Principle is crystallizing intracellular water.  Usually nitrous oxide is used.  Ideal for ectocervical lesion associated with satisfactory colposcopy  Not used for CIN 3
  • 36.  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.
  • 37.  ELECTRO DIATHERMY  Uses unipolar electrode  8-10 mm depth can be destroyed.
  • 38. ADVANTAGE DISADVANTAGE Favorable safty profile No tissue specimen for histopathological 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
  • 39. EXCISION TREATMENT MODALITIES  indicated for unsatisfactory colposcopy with histological CIN, recurrent AGC cytology.  MODALITIES  LEEP  Cold knife conization.  Laser conization.
  • 40.  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
  • 41. 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
  • 42.  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.
  • 43. 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.
  • 45.  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.