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UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
UICC
HPV andCERVICALCANCERCURRICULUM
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
01 Chapter 2.a.
Screening and diagnosis –
Visual screening for cervical
neoplasia
R. Sankaranarayanan, MDHead, Screening Group
International Agency for Research on Cancer (IARC)
Lyon, France
C. Santos, MDChairman, Gynaecologic Oncology Department
Instituto de Endermedades Neoplásicas
Lima, Peru
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
02Visual screening for cervical neoplasia
(1)
• Visual screening
- with acetic acid (VIA):
examination of the uterine cervix with the naked eye under
bright light from a halogen focus lamp 1 minute after
application of 3-5% dilute acetic acid
- with Lugol’s iodine (VILI):
visualisation immediately after application of Lugol‟s
iodine
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
03Visual screening for cervical neoplasia
(2)
• Simple, widely feasible and affordable
• Allow for “see and treat” sessions
• Can be provided by a wide range of health
workers including doctors, nurses, midwives
and primary health care workers
• Issue: subjective in nature and provider
dependent tests
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
04Challenges
• Quality assurance for visual screening
- visual screening is dependent on the full visibility of the
transformation zone of the cervix
- difficult interpretation of both VIA and VILI in
postmenopausal women
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
05Accuracy of screening tests in developing
countries: range in sensitivity and specificity
Test Sensitivity Specificity
Cytology 31-78% 91-99%
HPV testing 61-90% 62-94%
VIA 50-96% 44-97%
VILI 44-93% 75-85%
Source: http://screening.iarc.fr/study_acc.php?lang=1
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
06Instruments and supplies
• Examination table
• Light source
• Bivalved speculum
• Instrument tray
- cotton swabs
- examination gloves
- 4% acetic acid ( or white vinegar )
- Lugol‟s iodine solution
- 0.5% chlorine solution
- report form for the result
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
07VIA test
• Inspect external genitalia
• Insert speculum and reveal cervix
• Visually check for evidence of infection
• Remove discharge
• Identify cervical os and squamocolumnar
junction (SCJ)
• Apply acetic acid to cervix, wait 1 minute
• Inspect SCJ and any lesion found
• Document the findings
• Remove any remaining acetic acid
• Remove the speculum
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
08Reporting VIA test results (1)
• Negative or Normal (-) is scored when any of
the following occur:
I. No acetowhite lesions
II. Bluish white lesions or faint patchy lesions or
undefined lesions without definite margins
III. Polyp protruding from the os taking up acetowhite
IV. Nabothian cysts taking up acetowhite and appearing
as whitish acne (pimples)
V. Faint line-like acetowhitening at the junction of
columnar and squamous epithelium
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
09Reporting VIA test results (2)
• Negative or Normal (-) is scored when any of
the following occur:
VI. Acetowhite lesions far away from the transformation
zone
VII. Streak-like acetowhitening
VIII. Dot-like areas in the endocervix, which are due to
grape-like columnar epithelium staining with acetic
acid
IX. When there are shiny or cloudy-white lesions with ill-
defined, indefinite margins
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
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10
VIA negative: No acetowhite areas seen.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
11
VIA negative: No definite acetowhite areas. The squamocolumnar
junction (SCJ) is accentuated as a white line after application of 4%
acetic acid.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
12
VIA negative: Ectropion: the SCJ is prominent after the application
of acetic acid. Note the translucent, glassy, pinkish white
membrane like immature squamous metaplastic epithelium
(arrows).
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
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13
VIA negative: The streak-like irregular acetowhite areas are due to
squamous metaplasia. There are satellite lesions detached from
the SCJ.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
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14
VIA negative: The Nabothian cysts appear as pimple-or button-like
areas after the application of acetic acid.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
15Reporting VIA test results
• Positive (+) is scored when any of the
following occur:
- Distinct, well defined, dense, opaque or dull white or
oyster white acetowhite areas touching the
squamocolumnar junction (SCJ) or touching the external
os (if SCJ is not seen)
- Circumferential white lesion surrounding the os
- The whole cervix turns white after application of acetic
acid
• Invasive cancer is scored if there is clinically
visible ulcero-proliferative growth on the cervix
that bleeds on touch
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
16
VIA positive: Note the opaque acetowhite areas arising from the
SCJ in the anterior lip.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
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VIA positive: Note the thick, densely opaque, well-defined
acetowhite lesion touching the SCJ in the lower lip.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
18
VIA positive: Note the dense acetowhite area all over the cervix
involving all the four quadants and extending into the cervical canal.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
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VIA positive, invasive cancer: There is a circumferentially raised,
dull, chalky-white lesion with irregular surface and several bleeding
points on touch involving the cervix.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
20
VIA positive, invasive cancer: The dense acetowhite area with
irregular surface area is partly obscured by bleeding.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
21
VIA positive, invasive cancer: There is an ulceroproliferative
growth with acetowhitening and bleeding.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
22
VIA negative: The Nabothian cysts appear as pimple-or button-like
areas after the application of acetic acid.
UICC HPV And Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, Carlos Santos MD
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
23VILI test
• Can be used immediately after VIA screening
for additional information
• Reaction with glycogen in the cervical
epithelium:
- Normal squamous epithelium tint brown or black
- Normal columnar epithelium, immature squamous
metaplastic epithelium and cervical neoplasia remain
coulourless
- Can turn mustard or saffron yellow in the case of
cervical neoplasia
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
24Reporting VILI test results
• VILI negative (-) is scored when any of the
following occur:
- The squamous epithelium is black and the columnar
epithelium does not change colour after the application
of iodine.
- There are patchy areas of no or partial uptake of iodine
in the transformation zone corresponding to area of
immature squamous metaplasia.
- There are patchy iodine non-uptake areas, scattered all
over the cervix, not restricted to the transformation zone.
- There are pepper-like iodine non-uptake areas in the
squamous epithelium.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
25
VILI negative: The squamous epithelium is black and the columnar
epithelium does not change colour after the application of iodine.
Columnar epithelium has not
taken up iodine
Squamous
epithelium
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
26
VILI negative: Squamous epithelium remains brown. There are
patchy areas of no or partial uptake of iodine in the transformation
zone corresponding to area of immature squamous metaplasia and
inflammation.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
27
VILI negative: There are patchy iodine non-uptake areas, scattered
all over the cervix, not restricted to the transformation zone. This is
characteristic of chronic cervicitis.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
28
VILI negative: There are pepper-like iodine non-uptake areas in
the squamous epithelium due to cervical ulceration due to
inflammation.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
29
VILI negative: The iodine negative, irregular yellow areas are
detached from the squamocolumnar junction and constitute
„satellite‟ lesions.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
30Reporting VILI test results
• VILI positive (+) is scored
when dense, thick, bright, mustard or saffron yellow
iodine-negative areas are seen in the cervix, close to the
squamocolumnar junction or when the entire cervix
appears mustard yellow.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
31
VILI positive: There is a saffron-yellow iodine non-uptake area in
the anterior lip abutting the squamocolumnar junction.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
32
VILI positive: There is a mustard yellow lesion with no iodine
uptake in the anterior lip touching the squamocolumnar junction.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
33
VILI positive: There is a mustard yellow iodine non-uptake area in
the anterior lip abutting the squamocolumnar junction.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
34
VILI positive: There is a dense, mustard yellow iodine non-uptake
area abutting the squamocolumnar junction in the anterior lip of the
cervix with irregular, angular margins.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
35
VILI positive, invasive cancer: There is a large, dense, saffron
yellow iodine non-uptake area with irregular surface, involving all
the four quadrants and extending into the cervical canal.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
36
VILI positive, invasive cancer: There is a large, mustard yellow
iodine non-uptake area with irregular surface, involving all the four
quadrants of the cervix and extending into the cervical canal.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
37
VILI positive, invasive cancer: There is a large, thick mustard
yellow area in the cervix with irregular, nodular surface contour.
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
38Randomised controlled trial of the
screen and treat approach for cervical
cancer prevention in South Africa
Characteristic HPV test & treat
N=2163
VIA & treat
N=2227
Delayed evaluation
N=2165
6m post-randomisation evaluated womenCIN2+ prevalence
1879
15 (0.8%)
1929
43 (2.2%)
1859
65 (3.5%)
CIN2 prevalence 12m post-randomisation
25 (1.4%) 54 (2.9%) 92 (5.45)
Source: Denny et al., JAMA, 2005; 294:2173-81
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
39Cluster randomised trial of visual screening for cervical
cancer in rural South India: Dindigul District cervical
screening study, Tamil Nadu, India (1)
Excluded (n=13)
All not meeting the inclusion criteria
Screened
(n=31,343)
Screen positive
(n=3088, (9.9%))
Cancer cases
(n=167)
CR: 60.9/100 000 PYO
ASR: 75.2/100 000 PYO
Screen detected
(n=67)
Symptomatic
(n=100)
Cancer deaths
(n=83)
CR: 30.2/100 000 PYO
ASR: 39.6/100 000 PYO
VIA group
(n=49,311
)(in 57 clusters)
274 430 PYO
Cancer deaths
(n=92)
CR: 51.5/100 000 PYO
ASR: 56.7/100 000 PYO
Cancer cases
(n=158)
CR: 88.6/100 000 PYO
ASR: 99.1/100 000 PYO
Control group
(n=30,958)
(in 56 clusters)
178 781 PYO
Randomisation
Eligible Population
113 clusters
(n=80 282)
Source: Sankaranarayanan et al., Lancet, 2007;370:398-406
CR: crude rate
ASR: Age-Standardised
Incidence Rates
Flow chart of study results
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
40Cluster randomised trial of visual screening for cervical
cancer in rural South India: Dindigul District cervical
screening study, Tamil Nadu, India (2)
Overall and age-specific hazard ratio for incidence of all cervical
cancers and for cervical cancer deaths
Hazard ratio (95% CI)*
Control group 1.00
Intervention groupOverall
Cervical cancer incidenceCervical cancer deaths
30-39 yearsCervical cancer incidenceCervical cancer deaths
40-49 yearsCervical cancer incidenceCervical cancer deaths
50-59 yearsCervical cancer incidenceCervical cancer deaths
0.75 (0.59-0.95)0.65 (0.47-0.89)
0.62 (0.40-0.96)0.34 (0.18-0.66)
0.82 (0.55-1.24)0.55 (0.31-1.00)
0.76 (0.50-1.16)0.99 (0.58-1.66)
* C.I.: Confidence interval
Source: Sankaranarayanan et al., Lancet, 2007;370:398-406
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
Slide
41Cluster randomised trial of visual screening for cervical
cancer in rural South India: Dindigul District cervical
screening study, Tamil Nadu, India (3)
Cumulative incidence of cervical cancer (2000-2006)
Source: Sankaranarayanan et al., Lancet, 2007;370:398-406
a)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
0 1 2 3 4 5 6 7
Year
Inc
ide
nc
e (
/10
00
)
Intervention group Control group
b)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
0 1 2 3 4 5 6 7
Year
Inc
ide
nc
e (
/10
00
)
Intervention group Control group
c)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
0 1 2 3 4 5 6 7
Year
Inc
ide
nc
e (
/10
00
)
Intervention group Control group
d)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
0 1 2 3 4 5 6 7
Year
Mo
rta
lity
(/1
00
0)
Intervention group Control group
Overall Stage 1B or worse disease
At stage 2 or worse Cumulative mortality from
cervical cancer in the
intervention and control groups
UICC HPV and Cervical Cancer Curriculum Chapter 2.a. Visual screening for cervical neoplasiaR. Sankaranarayanan MD, C. Santos MD
This presentation is available at
www.uicc.org/cervicalcancercurriculum
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42
Thank you