Cervical intra epithelial neoplasia

1. Aboubakr Elnashar
Benha university, Egypt
https://www.facebook.com/groups/227744884091351/

2. 2. PREMALIGNANT STAGE
Cervical intraepithelial neoplasia (CIN): includes
Dysplasia & CIS
CIN 1 = Mild D.
CIN 2= Moderate D.
CIN 3= Severe D or CIS.
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3. CIN I
CIN II
CINIII Aboubakr Elnashar

4. Squamous intraepithelial lesion (SIL): includes HPV
& CIN.
Low grade SIL= CIN 1 or HPV.
High grade SIL= CIN 2 or 3
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6. HPV types
Oncogenic potential HPV TYPES
LOW 6, 11,14,43,44
INTERMEDIATE 31,33,35,51,52,
HIGH 16,18, 45, 56
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7. 13 high-risk HPV
16, 18,
31, 33, 35, 39
45,
51, 52, 56, 58, 59,
68.
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8. Transition time of CIN
Stages Mean years
Normal to CIN 1-2 1.62
Normal to CIN 2-3 2.2
Normal to CIN 3 4.51

9. Clinical picture
Symptoms:
No symptoms: majority of cases
Postcoital bleeding
Vaginal spotting
Abnormal vaginal discharge
Suggestive findings
Clinically suspicious cervix

10. II. METHODS OF
CERVICAL CANCER
SCREENING
A. Cytological
1. Conventional Pap. Smear
2. Liquid-based monolayers: LBC
3. Automated cytological screening
B. HPV testing
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11. C. Visual
1. Visual inspection of the cervix
a. Visual inspection with acetic acid (VIA)
b. Visual inspection with acetic acid and magnification (VIAM)
c. Visual inspection with Lugol’s Iodine (VILI)
2. Colposcopy.
3. Gynocular
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12. A. CYTOLOGY
1. Conventional Pap test
used for ≥50 y all across the globe.
widely used for in most developed countries
Meets all the requirements for mass screening:.
 Fairly tolerated by patients
Easy to administer
 Reasonable sensitivity & specificity.
Detection of endocervical lesions.
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13. Precautions:
No sexual intercourse, vaginal douche, medication
No lubrication, powder, pelvic examination , acetic
acid
Instruments & materials:
Speculum
Spatula:
Cytobrush or cotton tipped swab for the endocervical canal
Ayre s spatula for the ectocervix
Fixative
Jar
Slide
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14. Steps:
Taking the sample: from the ectocervix and
endocervix, either with a spatula or brush
Smearing: circular motion
Fixation: Ethyl alcohol, Coating spray
Staining:
Examination under
a microscope by specially
trained technologists and
doctors.
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19. CINIII
CINIII
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20. Limitations
 Moderate to low sensitivity:
 High rate of false-negative test results 20-40%
 Women must be screened frequently
 Rater dependent
 Requires:
 Complex infrastructure: Complex laboratory test
 Trained cytologist
 Multiple visits
 Continuous monitoring to maintain high-quality results
 Results are not immediately available
 Less accurate among post-menopausal women
 Impossible to locate the lesion.
 Usually available only in large cities in many
countries Aboubakr Elnashar

21. Aboubakr Elnashar
Frequency of Pap test
CDC recommendation
21 to 29y: Pap test /3 y.
30 to 65y: Pap test /3 y or
Pap test plus HPV test/5 y.

22. 2. Liquid-based monolayers
(ThinPrep, CytoRich)
Steps:
•Cells are collected using a brush instead of a
spatula.
•Head of the brush is vigorously shaken or broken off
into a small pot of liquid containing preservative
solution.
•The sample is filtered or centrifuged to remove
excess blood and debris.
•The cells are then transferred to the slide in a
“mono” layer.
•Staining.
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23. Advantages:
•It removes most mucus, protein& fresh blood cells,
•distributes the cells uniformly
•improves fixation
•maintains diagnostic clusters
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24. LBC Vs Conventional Pap
More expensive
Repeat smear rates: 1 to 2% Vs 9%
Less false negative rate
No difference in the relative sensitivity.
No difference in the relative specificity, when H
and L- GSIL were considered as cutoff.
Better in predicting CIN
It is the preferred tool for cervical cytology
screening
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26. 3. Automated Pap smears
To reduce errors by using computerized analysis to
evaluate Pap smear slides.
1. Autocyte
•Composed of an algorithmic & neural network
scanner
•Scans the slides & records images of 128 of the
most abnormal fields found on the slide, with the
most significant abnormality found in the center.
•It reduces costs & shortens screening time.
•Detects 97.2% of the abnormal tests (Koss et al,1994).
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28. 2. AutoPap.
The material on the slide is reviewed and scored
based on an algorithm, as to the likelihood of an
abnormality being present.
Typically, it does not show the cytotechnologist
which of the cells are likely to be abnormal.
Variety of visual characteristics, such as shape and
optical density of the cells, are included in the
algorithm.
•It reviews all normal & satisfactory smears
•As a primary screener, it removes 30 % of slides
from the workload
•97% sensitivity (Lee et al, 1997)Aboubakr Elnashar

29. B. HPV TESTING
Role of HPV as a causative agent of cervical
cancer has been well established.
However, most HPV infections in young women
regress rapidly, without causing clinically significant
disease.
infection is a marker of sexual activity than of
cervical cancer risk.
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30.  Hybrid Capture II kit (HC II, Qiagen Inc., USA)
Approved by FDA : frequently used.
The sample is collected similar to Pap, with a
cervical swab from TZ and placed into transport
medium.
 Detects whether a person is infected with one or
more of the 13 high-risk HPV viral types (types16,
18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68).
It is used as
Routine screening test above 30 to 35 y
To evaluate equivocal Pap test. ASCUS or LGSIL:
Oncogenic HPV: Colposcopy.
≥35 y: HPV testing/5 years & if +ve: Pap smear
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31. •Negative predictive value: very high
•HPV testing could augment but not replace
cytological screening
Sensitivity for detecting CIN 2–3 lesions: 45.7 to
80.9%
Specificity: 91.7 to 94.6%.
HPV testing (Qiagen HCII)
most objective and reproducible of all cervical
screening tests
less demanding in terms of training and quality
assurance.
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32. HPV testing
sophisticated lab
unaffordable ($20 to $30/test) in less-developed
countries.
HPV DNA- PCR testing (HPV typing): [Current
technique (HC2) Hybrid Capture 2]
Isolated HPV types could be detected.
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33. Care HPV test (Qiagen Inc. USA)
Detect several types of HPV rapidly (within 3 h)
No need:
specially trained personnel or
sophisticated lab.
{simplicity and rapid completion}: screening and
clinical follow-up to be completed on the same day.
low cost: $8/test
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34. C. VISUAL
1. Visual examination of cervix
a. Visual inspection after application of acetic acid
(VIA)
b. VIA with magnification (VIAM)
c. Visual inspection after application of Lugol’s iodine
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35. Effects of acetic acid:
Coagulates the proteins of the nucleus &
cytoplasm: protein opaque & white.
Dehydrates the cells: cytoplasmic volume is
reduced & the reflection is increased.
Duration:
appears after 20 seconds
disappears after 2 minutes.
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36. Category Clinical Findings
Negative No acetowhite lesions or
faint acetowhite lesions;
polyp,
cervicitis, inflammation,
Nabothian cysts.
Positive Sharp, distinct, well-defined,
dense (opaque/dull or oyster white) acetowhite with
or without raised margins touching SCJ;
leukoplakia and
warts.
Suspicious
for cancer
ulcerative, cauliflower-like growth or
ulcer; oozing and/or bleeding on touch.Aboubakr Elnashar
2 . Visual inspection with acetic acid (VIA)

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38. Normal NAAT
Positive
Suspicious for cancer
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39. VIA Performance:
Source: Adapted from Gaffikin, 2003
Sensitivity Specificity
Pap 47-62 60-95
VIA 76-84 79-83
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3. Visual Inspection with Acetic Acid Using
Magnification (VIAM) Gynoscopy = Aided VIA
 visualization of cervix after application of aa using low power magnification
(2.5x to 4x)
 Inexpensive, easy to use portable system, which can be used to screen
cervical cancer in developing countries.
 Sensitivity: 80%
 Specificity: 95% compared to Pap smear
Magnascope (4X)

41. Aboubakr Elnashar
4. Visual inspection after application of Lugol’s
iodine
Test performance:
(Sankaranarayanan et al., 2008).
SpecificitySensitivity
85.576.8VIA
85.491.7VILI

42. Aboubakr Elnashar
Categories for VILI test results:
Category Clinical Findings
Negative Squamous epithelium turns brown
Columnar epithelium does not change
color; or
Irregular, partial or non-iodine uptake
areas.
Positive Well-defined, bright yellow iodine non-
uptake areas touching SCJ or close to the
os if SCJ is not seen.
Suspicious
for cancer
Ulcerative, cauliflower- like growth or
Ulcer; oozing and/or bleeding on touch.

43. Aboubakr Elnashar
 VILI: test-positive
 Well-defined
 bright yellow iodine non-uptake
areas
 touching the SCJ

44. 2. Colposcopy
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45. Colposcope :
Microscope
Low-power, stereoscopic, binocular field
Powerful light source
Moving system
The most common indication:
positive screening tests: positive cytology
positive on VIA.
Biopsies from suspicious areas
Endocervical curettage:
when the colposcopy is unsatisfactory, i.e. scj
cannot be visualized.
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48. Swede score
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49. Swede score of 4 and above:
Punch biopsies of the cervix
Swede score 6 and above:
immediate tt
with cold coagulation under visualisation with the
Gynocular and local anaesthesia.
patients not suitable for cold coagulation or with
biopsies revealing microinvasive cervical disease or
worse: appropriate diagnostic workup and
management protocol.
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51. 3. Gynocular
Mini colposcope
portable colposcope
Easy to use:
Handheld or used with a tripod
Pocket-size battery:
Battery operated (2 h of working time/charge)
Provide gold-standard examination:
Red-free/green filter mode
Capture digital images
Take videos
low-resource countries. Aboubakr Elnashar

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53. charger and mounting clip
for camera tripod.
lens, green filter,and warm
white LED illumination.
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56. III. SCREENING IN
DEVELOPING
COUNTRIES
Difference between developing & developed
countries
I. Higher incidence: 80%
II. Higher mortality: 90%
III. Different risk factors
IV. Poor financial, human & technical resources
V. Inadequate follow up
Screening used in the developed world is
inappropriate in developing countries (Singer,1995)Aboubakr Elnashar

57. Alliance for Cervical Cancer Prevention
2009
1. optimal age-group for cervical cancer screening
to achieve the greatest public health impact is
30–39-y-olds.
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58. 2. Cytology-based screening programs using Pap
smears have been shown to be effective in
developed countries, sustaining high-quality
cytology- based programs is difficult in low-resource
settings.
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59. 3. The most efficient and effective strategy
VIA or
HPVDNA testing and then to treat using
cryotherapy.
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60. TREATMENT
I. Ablative (destructive)
1. Cryotherapy
2. Cold coagulation
3. Laser vaporization
II. Excisional
A . LETZ B. Conization:
1. LEEP
2. Cold knife (CKC)
3. Laser
III. Hysterectomy

61. CIN: WHO Recommendation 2014.
CIN 1:
(i) immediate tt
(ii) follow the woman and then tt if the lesion is
persistent or progressive after 18 to 24 months.
CIN 2 and CIN 3:
Cryotherapy or LEEP.
AIS (adenocarcinoma in situ)
CKC

62. Strategy
Three visits strategy
one for screening
one for colposcopy,
one for treatment: poor compliance, especially
among rural women.
Single visit: see-and-treat strategy
satisfactory results
no significant extra morbidity
[Emam et al, 2009].
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63. See & treat (Single visit diagnosis & tt)
•It means
(Cryo therapy, cold coagulator or LEEP) at first visit to
women with (VIA or colposcopic) findings suggestive of
SIL.
•Advantages:
False negative histology is low (4.7% )
Reduce waiting lists & anxiety
•Disadvantages:
Over tt of insignificant lesions
•It should be limited to HGSIL (Pastner,1994)

65. III. Hysterectomy
Indications
1. Other gynecological conditions:
.fibroid, prolapse, endometriosis, PID .
2. Refuse all other forms of therapy
3.SIL at limits of conization specimen
4. Poor compliance with follow-up
Sterilization is not an indication

66. Treatment of CIN during pregnancy
•Abnormal cytology Colposcopy
•Colposcopically directed punch biopsy or
small loop biopsy
•Knife or LLE cone: rarely indicated
•Colposcopy/ 3 m to ensure that the lesion is not
progressing
•CIN 3: treatment after delivery

67. Prof. Aboubakr Elnashar
Benha University Hospital, EGYPT
E-mail: elnashar@hotmail.com