screening for cancer cervix

SCREENING
FOR
CERVICAL
CANCER
Prof.
Aboubakr
Elnashar
Benha
university,
Egypt
Aboubakr
Elnashar
CONTENTS
1.
MAGNITUDE
OF
THE
PROBLEM
2.
PREMALIGNANT
STAGES
3.
RISK
FACTORS
4.
SCREENING
STRATEGY
5.
METHODS
OF
SCREENING
Aboubakr
Elnashar

1.
MAGNITUDE
OF
THE
PROBLEM
▪World
wide:
3
rd
most
common
female
cancer
▪
Developing
countries:
80
%
of
all
cases
▪
Egypt:
2
nd
most
common
female
cancer
▪
Developed
countries:
decrease
since
mid
1980
s
Aboubakr
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❑Incidence
of
Gynecologic
Cancers
in
Egyptian
Women
0
5
10
15
20
25
Breast
Cancer
Cervical
Cancer
Ovarian
Cancer
Uterine
Cancer
Percent
Source:
GLOBOCAN
2000.
Aboubakr
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CIN
(%)
N
o
Study
University
Year
Author
1.07
4458
Hospital
Cairo
1987
Hammad
et
al
3.1
5453
Community
Suez
canal
2007
Abd
El
All
et
al
3.1
25522
Hospital
Ain
Shams
2004-
2010
Shalakany
(2012)
5.8
3600
Hospital
Minia
2014
Sanad
et
al
1.3
6173
Alexandria
2015
Abdelhady
et
al
3.2
1600
Community
Assuit
2017
Elmoselhy
et
al
3.00
46806
Total
❑
Incidence
▪
CIN
in
Egypt
(Elnashar,
2019)
Aboubakr
Elnashar
❑
Cx
ca
in
Egypt:
▪
0.04%
(AbdelAll
et
al,
2007)
▪
0.06%
populations
[Feraly
et
al,
2010)
▪
8th
among
the
most
common
females'
cancers
(National
Cancer
Institute
registry
for
the
years
2002-
2004)
▪
increasing
incidence
from
2002
to
2004
[Elattar,
2004)
▪
increase
by
34.0%
from
2013
to
2050
[Ebrahim
et
al,
2014)
Aboubakr
Elnashar

Incidence
rates,
crude
rates,
females,
Egypt
2008–2011
National
Population-Based
Registry
Program
of
Egypt.
(2014)
Crude
rate
%
Breast
35.8
32
Ovary
4.6
4.1
Uterus
unspecific
2.5
2.3
Cervix
uteri
1.3
1.2
Corpus
uteri
0.7
0.6
Vagina
0.2
0.14
Vulva
0.1
0.09
Other
female
genital
0.1
0.05
Aboubakr
Elnashar
Cervical
Cancer
in
Egypt
(Ibrahim
AS
et
al.
2014)
0
5
10
15
20
25
30
35
<
45
years
45
-
59
years
≥
60
years
ASR
Incidence/100,000
W
Aboubakr
Elnashar

2.
PREMALIGNANT
STAGE
❑
Cervical
intraepithelial
neoplasia
(CIN):
includes
▪
Dysplasia
&
CIS
▪
CIN
1
=
Mild
D.
CIN
2=
Moderate
D.
CIN
3=
Severe
D
or
CIS.
Aboubakr
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CIN
I
CIN
II
CINIII
Aboubakr
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❑Squamous
intraepithelial
lesion
(SIL):
includes
▪
HPV
&
CIN.
▪
Low
grade
SIL=
CIN
1
or
HPV.
High
grade
SIL=
CIN
2
or
3
Aboubakr
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3.
RISK
FACTORS
I.
Medical
risk
factors
▪Cervical
high-risk
HPV
infection:
▪99%
of
cervical
cancer
&
high
grade
CIN
are
associated
with
HPV
▪Types
16
and
18:
responsible
for
70%
of
all
cervical
cancers.
▪Parity:
▪Multiparity
▪4
live
births
▪Early
age
of
1
st
birth
▪Immunosuppression
Aboubakr
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II.
Demographic
risk
factors
▪Ethnicity
(Latin
American
countries,
U.S.
minorities)
▪Low
socioeconomic
status
▪Age
III.
Behavioral
risk
factors
▪Infrequent
or
absent
cancer
screening
Pap
tests
▪Early
coitarche
▪Multiple
sexual
partners
▪Male
partner
who
has
had
multiple
sexual
partners
▪Tobacco
smoking
▪Dietary
deficiencies:
folic
ac,
vit
A
Aboubakr
Elnashar
HPV
types
Oncogenic
potential
HPV
TYPES
LOW
6,
11,14,43,44
INTERMEDIATE
31,33,35,51,52,
HIGH
16,18,
45,
56
Aboubakr
Elnashar

❑13
high-risk
HPV
▪
16,
18,
▪
31,
33,
35,
39
▪
45,
▪
51,
52,
56,
58,
59,
▪
68.
Aboubakr
Elnashar
❖Cervical
cancer
is
a
preventable
disease
1.
Has
a
characteristic
natural
course
with
a
slow
progression
through
a
premalignant
stage
2.
A
premalignant
stage
can
be
detected
by
noninvasive
means:
Pap
smear,
VIA
3.
An
effective
tt
for
the
premalignant
lesions
Aboubakr
Elnashar

4.
SCREENING
STRATEGY
❑Methods
of
Prevention
▪
Primary:
▪
Avoidance
of
the
precipitating
&
risk
factors
▪
Counseling
▪
Vaccination
▪
Secondary:
▪
Screening
▪
Early
detection
▪
Tertiary:
▪
Treatment
or
mitigation
of
damage
Aboubakr
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▪
Screening:
▪
Definition
▪
Systematic
application
of
a
test
in
▪
asymptomatic
person
▪
to
identify
pre
clinical
lesions.
▪
Types
:
▪
Selective:
Screening
high
risk
groups
▪
Mass:
Screening
all
population
Aboubakr
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▪
In
developing
countries
(lower
and
middle-income
countries
(LMICs)
1.
Poor
financial,
human
&
technical
resources
2.
Higher
incidence:
80%
of
cases
3.
Higher
mortality:
90%
4.
Different
risk
factors
5.
NO
screening
guidelines
.
6.
Decreased
access
to
treatment
7.
Inadequate
follow
up
▪
Screening
used
in
the
developed
world
is
inappropriate
in
developing
countries
Aboubakr
Elnashar
▪
In
Higher
-income
counteries
▪
have
guidelines
for
screening
women
▪
These
guidelines
define
not
only
the
target
population
for
screening,
but
also
▪
screening
methods,
intervals,
and
▪
appropriate
interventions
depending
on
test
results
▪
The
incidence
of
cervical
cancer
has
decreased
by
approximately
80%
Aboubakr
Elnashar

Choosing
an
appropriate
screening
modality
▪
The
three
main
modalities
of
screening
in
use
▪
HPV
testing
▪
Cytology
▪
VIA
▪
Selection
of
method
depends
on
existing
resources
rather
than
differences
in
efficacy
▪
In
good
resource
settings:
▪
Validated
primary
HPV
screening:
The
most
effective
method
▪
In
centers
with
an
established
cytology
program
with
good
quality
control
may
continue
with
cytology.
▪
In
limited
resource
settings
one
may
screen
with
VIA.
Aboubakr
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▪
Pap-only
testing
▪
performed
every
3
y
▪
Pap-HPV
cotesting
▪
Performed
every
5
y
in
women
older
than
30
with
past
normal
screening.
▪
Until
2018,
all
3
organizations
recommended
cotesting
as
the
preferred
screening
algorithm
for
women
ages
30
to
65.
▪
Patients
with
a
history
of
abnormal
test
results
require
more
frequent
testing
as
recommended
by
the
ASCCP,
2012
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ASCCP,
ACOG
Aboubakr
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▪
In
L&MIC:
WHO
Aboubakr
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▪
In
HIC:
Preventive
Services
Task
Force,
2018
▪
For
average-risk
women
▪
Age:21–29:
cervical
cytology
alone
every
3
years.
▪
30–65
years,
screening
options
include
1.
Cytology
alone
every
3
years
2.
High-risk
HPV
testing
alone
every
5
years,
or
3.
Cotesting
every
5
years.
▪
Do
not
screen
for
cervical
cancer.
1.
Women
younger
than
21
y
2.
women
older
than
65
years
with
adequate
prior
screening
3.
women
who
have
had
a
total
hysterectomy
Aboubakr
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▪
Risk
Assessment
▪
All
women
aged
21
to
65
years
are
at
risk
for
cervical
cancer
because
of
potential
exposure
to
high-risk
HPV
types
through
sexual
intercourse
and
should
be
screened.
▪
Certain
risk
factors
further
increase
risk
for
cervical
cancer
1.
HIV
infection
2.
Compromised
immune
system
3.
In
utero
exposure
to
diethylstilbestrol
4.
Previous
treatment
of
a
high-grade
precancerous
lesion
or
cervical
cancer.
▪
Women
with
these
risk
factors
should
receive
individualized
follow-up.
Aboubakr
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5.
METHODS
OF
CERVICAL
CANCER
SCREENING
A.
Cytological
1.
Conventional
Pap.
Smear
2.
Liquid-based
monolayers:
LBC
3.
Automated
cytological
screening
B.
HPV
testing
Aboubakr
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C.
Visual
1.
Visual
inspection
of
the
cervix
a.
Unaided
b.
Visual
inspection
with
acetic
acid
(VIA)
c.
Visual
inspection
with
acetic
acid
and
magnification
(VIAM)
d.
Visual
inspection
with
Lugol’s
Iodine
(VILI)
Aboubakr
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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.
Aboubakr
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❑Precautions:
No
▪
Sexual
intercourse
▪
Vaginal
douche
▪
Medication
▪
Lubrication
▪
Powder
▪
Pelvic
examination
▪
Acetic
acid
Aboubakr
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▪
Instruments
&
materials:
▪
Speculum
▪
Spatula:
▪
Cytobrush
▪
cotton
tipped
swab
for
the
endocervical
canal
▪
Ayre
s
spatula
for
the
ectocervix
▪
Fixative
▪
Jar
▪
Slide
Aboubakr
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❑Steps:
1.
Taking
the
sample:
▪from
the
ectocervix
and
endocervix
▪with
a
spatula
or
brush
2.
Smearing:
circular
motion
3.
Fixation:
▪Ethyl
alcohol
▪Coating
spray
4.
Staining:
5.
Examination
under
a
microscope
by
specially
trained
technologists
and
doctors.
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❑Limitations
▪Requires:
▪Complex
infrastructure:
Complex
laboratory
test
▪Trained
cytologist
▪Multiple
visits
▪Continuous
monitoring
to
maintain
high-quality
results
▪Results:
▪Moderate
to
low
sensitivity:High
rate
of
false-negative
test
results
20-40%:
Women
must
be
screened
frequently
▪Rater
dependent
▪Not
immediately
available
▪Less
accurate
among
post-menopausal
women
▪Impossible
to
locate
the
lesion.
▪Available:
only
in
large
cities
in
many
countries
Aboubakr
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2.
Liquid-based
monolayers
(ThinPrep,
CytoRich)
❑Steps:
1.
Cells
are
collected
using
a
brush
instead
of
a
spatula.
2.
Head
of
the
brush
is
vigorously
shaken
or
broken
off
into
a
small
pot
of
liquid
containing
preservative
solution.
3.
The
sample
is
filtered
or
centrifuged
to
remove
excess
blood
and
debris.
4.
The
cells
are
then
transferred
to
the
slide
in
a
“mono”
layer.
5.
Staining.
Aboubakr
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▪
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
Aboubakr
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Aboubakr
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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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Aboubakr
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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)
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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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▪
The
most
sensitive
modality,
suitable
for
screening
in
all
resource
settings.
▪
Even
a
single
round
of
HPV
testing
was
shown
to
significantly
reduce
the
incidence
of
cervical
cancer
▪
However,
it
is
expensive
and
not
widely
available.
▪
It
is
recommended
for
women
aged
over
30
years
using
validated
tests.
Aboubakr
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▪
Validated
tests
▪
are
those
that
have
demonstrated
efficacy
in
RCT
or
have
shown
test
accuracy
comparable
to
a
validated
test.
▪
Reported
as
▪
Detected/not
detected
for
a
pool
of
13
or
14
high-risk
HPV
genotypes
▪
Some
report
individual
genotypes
for
the
most
oncogenic
types
(HPV
16/18).
▪
Examples:
Hybrid
Capture
2,
careHPV,
Cobas,
Xpert,
Cervista,
APTIMA
etc.
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▪
The
high-risk
HPV-only
test
▪
utilizes
real-time
PCR
to
detect
▪
HPV
16,
▪
HPV
18,
and
▪
12
other
HPV
genotypes.
▪
Only
2
tests
are
approved
by
the
FDA
as
stand-alone
cervical
cancer
screening
tests
▪
Roche
Cobas
HPV
test
approved
in
2014
▪
Becton
Dickinson
Onclarity
HPV
assay
approved
in
2018.
▪
Other
HPV
tests
that
are
used
in
a
cotesting
strategy
▪
should
not
be
used
for
high-risk
HPV-only
testing
▪
because
their
performance
characteristics
may
differ.
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Aboubakr
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C.
Visual
inspection
with
acetic
acid
(VIA)
▪
Sensitivity
comparable
to
cytology
▪
Poor
specificity:
larger
number
of
women
will
require
further
triage
by
colposcopy
▪
Can
be
used
in
all
resource
settings
by
all
levels
of
healthcare
providers.
▪
Currently
it
is
the
only
test
that
can
be
used
in
low
resource
settings
with
considerable
accuracy
and
safety
but
in
future,
the
availability
of
affordable
HPV
testing
may
change
this
paradigm.
Aboubakr
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❑
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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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.
Visual
inspection
with
acetic
acid
(VIA)
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Normal
NAAT
Positive
Suspicious
for
cancer
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▪Visual
inspection
after
application
of
Lugol’s
iodine
Test
performance:
(Sankaranarayanan
et
al.,
2008).
Specificity
Sensitivity
85.5
76.8
VIA
85.4
91.7
VILI
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❑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.
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•
VILI:
test-positive
•
Well-defined
•
bright
yellow
iodine
non-uptake
areas
•
touching
the
SCJ
Aboubakr
Elnashar

screening for cancer cervix

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screening for cancer cervix