Dr Nurulhuda Samsudin
O&G dept. SGH
Introduction

Cervical cancer is the 3rd most frequent cancer among Malaysian
women.

The National Cancer Registry in 2006 reported that the age
standardized incidence (ASR) of cervical cancer was 12.2 per
100,000 women.

The proportion of deaths due to cervical cancer among all forms of
cancer deaths has been steadily increasing.

In 1998, cervical cancer was ranked 8th as cause of deaths in
Malaysia.
By 2006, deaths due to cervical cancers was ranked 3rd .


12.2 deaths for every 100,000 women dying from any form of
cancer was due to cervical cancer.
(National Cancer Registry Malaysia, 2006)
Preventable?-Yes

This increase in morbidity and mortality due is
unwarranted not only because:
- The definitive cause of cervical cancer is now
known i.e primarily due to high risk HPV
infection.
- The disease takes a long time to develop after
initial infection.

Unlike most other types of cancer, it is preventable
when precursor lesions are detected and treated.

Therefore, screening can reduce both the incidence
and mortality of cervical cancer.
Impact of cervical cytology screening on the incidence of invasive cervical
cancer in the United States.In Kurman R (ed): Blavstein’s Pathology of the
Female Genital Tract. 5th ed. New York, Springer-Verlag, 2002.
Screening modalities: Natural history
models

A clear understanding of the natural history of cervical
cancer is a key to planning and implementing a rationale
screening programme.
Risk factor for cervical cancer
Genital infection with a high-risk HPV
type.
 Early onset of sexual activity.
 Multiple sexual partners.
 Cigarette smoking.
 Immunocompromised.
 Low socioeconomic.


99.7% of all cervical cancer cases are associated with
persistent infection with high-risk HPV types.

HPV types 16 and 18 are the most common high-risk types
and account for 70% of all cervical cancer cases
worldwide.
-50% as a result of HPV-16 infection .
-20% as a result of HPV-18 infection.
HPV DNA
Detection
Sampling of cells
for cytology
Visual
inspection
Screening-Cytology

The mainstay of cervical cancer
screening for the last 60 years
has been the Papanicolaou test.

The Papanicolaou test, also
known as Pap smear, was
developed in the 1940s by
Georgios Papanikolaou.

It involves exfoliating cells from
the transformation zone of the
cervix to enable examination of
these cells microscopically for
detection of cancerous or
precancerous lesions.
1883-1962
The Transformation Zone
The optimal Pap smear contains:
 Sufficient mature and
metaplastic squamous cells to
indicate adequate sampling
from the whole of the
transformation zone.

Sufficient endocervical cells
to indicate that:
the upper limit of the
transformation zone was
sampled
to provide a sample for
screening of
adenocarcinoma and its
precursors
When to Perform
The best time is:
 Any time after the cessation of the period.
 Avoid smear-taking during menstruation.
 Avoid in the presence of obvious vaginal infection.
 Avoid within 48 hours of use of vaginal creams or
pessaries or douching.
 Avoid within 24 hours of intercourse.
 Avoid lubrication or cleaning of cervix with
preliminary pelvic examination.
Good communication with the pathologist is essential.

FORM
How to perform Pap Smear
Which Spatula?

Choose the contoured
end of the spatula that
best conforms to the
anatomy of the cervix
and the location of the
transformation zone
The Report Bathesda System
Liquid Based Cytology
BD
SurePath™
ThinPrep
FDA
Approved
MonoPrep
LBC vs Pap Test

Increase in sensitivity up to 12% better for the detection of abnormalities of
low-grade squamous intraepithelial lesions with LBC compared with the
Pap smear.

No difference between the specificity of LBC and Pap smear.

The English pilot study showed a statistically significant decrease in the
number of inadequate samples, from 9.1% with Pap slides to an average of
1.6% with LBC (87% reduction, p < 0.0001)

Reduced the pressure on the workforce because of fewer inadequate and
clearer to read samples.

Reduced levels of anxiety in women because fewer need repeat tests and
because they receive their results more quickly.

Remnant cells may be use for additional test e.g HPV DNA testing.
Visual Inspection
Involves 3 different
approaches:
 Visual inspection of
cervix with acetic acid
(VIA).

Visual inspection with
magnification (VIAM).

Visual inspection after
application of Lugol’s
iodine (VILI).
VIA

Applying 3% to 5% acetic acid and apply to the cervix liberally.

When acetic acid is applied to normal squamous epithelium, little
coagulation occurs in the superficial cell layer, as this is sparsely
nucleated.

Areas of CIN and invasive cancer undergo maximal coagulation
due to their higher content of nuclear protein (in view of the large
number of undifferentiated cells contained in the epithelium).

This prevent light from passing through the epithelium. As a
result, the sub-epithelial vessel pattern is obliterated and the
epithelium appears densely white.

In CIN, acetowhite is restricted to the transformation zone close
to the squamocolumnar junction, while in cancer it often involves
the entire cervix.
Test negative
Test Postivie
Suspicious for cancer
VILI

Lugol iodine is applied over the cervix.

Squamous epithelium contains glycogen, whereas precancerous lesions
and invasive cancer contain little or no glycogen.

Iodine is glycophilic and is taken up by the squamous epithelium, staining it
mahogany brown or black.

Columnar epithelium does not change color, as it has no glycogen.

Immature metaplasia and inflammatory lesions are at most only partially
glycogenated and, when stained, appear as scattered, ill-defined uptake
areas.

Precancerous lesions and invasive cancer do not take up iodine (as they
lack glycogen) and appear as well-defined, thick, mustard or saffron yellow
areas.
Test Negative
Test Positive
Suspicious for cancer
VIA vs VIAM vs VILI

VILI has the highest specifity, detecting 75 per cent
of all cases of HSIL compared with VIA and VIAM
which detected less than two third of cases.

VILI has higher sensitivity. The pooled sensitivity of
VILI 91.8 per cent (range 76-97.3%) compared to
those of VIA (76.9%) and VIAM (64.2%).

The yellow colour changes associated with a
positive VILI test result could be recognized with
much greater ease by trained health workers
compared with the acetowhite lesions associated
with VIA.
Management

Offer to treat immediately, (without
colposcopy or biopsy, known as the
“test-and-treat” or “single-visit”
approach).

Refer for colposcopy and biopsy and
then offer treatment if a precancerous
lesion is confirmed.
HPV Testing

HPV cannot be grown in culture and
detection of the virus relies on a variety
of techniques used in immunology,
serology, and molecular biology.
2 assays most widely used:
 PCR with generic primers
 The Hybrid Capture 2 assay.
HPV DNA Testing – Hybrid Capture Assay

The Hybrid Capture assay (hc2) is a batch test
based on hybridization in a solution of long
synthetic RNA probes.
-Probe B is complementary to the
genomic sequence of 13 high-risk types
(HPV-16,-18, -31,-33, -35, -39, - 45, 51, -52, -56, -58, -59 and -68).
-Probe A measures 5 low-risk (6, 11,
42,43,44) HPV types.
HPV DNA analysis - Sampling
Helthcare provider/Self
sample
Residual from LBC
HPV DNA testing vs Cytology
The HPV testing was:
 More sensitive in
detecting CIN2+ than
cytology (96.1% vs.
53.0%)
 Less specific (90.7%
vs. 96.3%).
Figure 1. A meta-analysis of seven primary HPV screening studies in six European countries investigated the
negative predictability of screening tests. After three years, the incidence of CIN3 was about 5 per 1,000 for
women who were negative for cytology tests. For women who were negative for HPV at baseline, by 72
months the incidence of CIN3 was about 2.5 per 1,000. Co-testing had marginally better predictability than HP
Which Screening Modalities?
Screening Guidelines – Who & Why?
Screening Guidelines: HPV Testing – Who & When
Prevalence of high-risk HPV and incident cases of
cervical cancer in the U.S., 2003–2005. Surveillance
Epidemiology and End Results (SEER) data for
incident cases among females aged 15 to 19 years and
50 to 64 years
ASCCP Guidelines
Malaysian Screening Programme Guidelines
Screening Guideline- Past, Current, Future

Cervical cancer screening in
Malaysia began in 1969, after
the intergration of the family
planning services into the
Maternal and Child Health
Program of the MOH.

It has expanded across the
country following the
launching of the “Active
Lifestyle” campaign, in 1995.

In 1998 “National Pap Smear
Screening Programme” was
setup, it offers screening to all
eligible women aged 20-65
years old for the first 2 years
than 3 yearly is the result is
normal.
The agencies involved:
 National Population and Familly
Development Board (LPPKN)
 University hospitals & Government
 Private clinics and hospitals.
 Military hospitals and other nongovernmental.
NGOs
 Agencies such as Federation of
Family Planning.
 Association of Malaysia and National
Cancer Society.
Current

Pap smear screening services had been
available for some time, nevertheless
studies have shown that half of all women
who died of cervical cancer did not
undergo Pap smear in the past five years
(Adeeb et al, 2008).

Reported that no reduction in the
prevalence of cervical cancer has been
noted in the country. (Wong et al.2008)
Improving our Screening
Programme
Review of current system.
 Empowering women.
 Informing and education.
