Cytologic Screening Programs
Luiz M. Collago and Lucilia Zardo
P rin c ip le s o f s c r e e n in g
S c r e e n in g P ro g ra m s a n d H P V D N A T e s t
C e rv ic a l C a n c e r a n d s c re e n in g
T h e R o le o f L a b o r a to r y in S c r e e n in g P r o g r a m s
C e rv ic a l C a n c e r In c id e n c e a n d M o r t a lit y W o r ld w id e
E ffic a c y o f S c r e e n in g
N e w D e v e lo p m e n ts in C y to lo g ic a l s c r e e n in g
D e s ig n o f S c r e e n in g P r o g r a m s
L iq u id -B a s e d C y t o lo g y (L B C )
F e a tu r e s o f S u c c e s s fu l S c r e e n in g P r o g r a m s
A u t o m a te d C y t o lo g y
L im it a t io n s o f S c r e e n in g P r o g r a m s
C o n c lu d in g R e m a rk s
S c r e e n in g P ro g ra m s a n d H P V V a c c in e
Principles of Screening
Screening of diseases gained significance in medicine at the end
of the nineteenth century, when public health authorities empha-
sized the importance of screening methods for certain diseases.
An example is the radiological screening of immigrants, searching
for infectious diseases such as tuberculosis in the USA.*
The idea of screening for early detection of cancer was accepted
in the 1920s after the development of exfoliative cytological tech-
niques initiated through the work of Babes2 and Papanicolaou.3 4
1941 George Papanicolaou demonstrated a test for the early detec-
tion of cervical cancer, contributing toward the creation of screen-
ing programs.4,5 Prevention and early diagnosis are major factors in
reducing morbidity and mortality resulting from neoplasia.6
Screening of diseases presumes a test or examination that can
detect the existence of a particular disease in a high-risk popula-
tion, asymptomatic or with minimum symptoms of the disease.
Systematic screening of diseases requires a series of elements
with the objective of decreasing mortality from a particular
disease. For this reason the World Health Organization lists
certain principles to guide the screening systems:7
1. The condition to be evaluated must be an important
cause of morbidity or mortality.
2. The natural history of the disease must be known as
well as forms of intervention in the pre-clinical stage
or with the disease installed.
3. The test used for screening must have a high level of
sensitivity and specificity.
4. The test to be applied must be low risk, with good
acceptability by the target population and the
5. In the case of positive tests, diagnostic methods for
confirming screening finds should be possible.
6. The test must be shown to be efficient in reducing
morbidity or mortality caused by the disease.
It therefore follows that screening of a particular disease
requires a precise test, easy to do, at a low cost, and the capabil-
ity of detecting the presence of a lesion. In principle this is not a
test for a definitive diagnosis, although it can in some situations
serve to indicate subsequent therapy.
Cervical Cancer and Screening
Cancer of the uterine cervix is an important cause of morbid-
ity and mortality among women worldwide and a leading
public health problem. It is the second most common cancer in
women, but the most common in developing countries.8
Because of the phases that precede the lesion in the natural
progress of invasive cervical cancer, and because they can be eas-
ily discovered and treated, the disease is well suited to screen-
ing programs. The Papanicolaou test is an established method
for examining the cells collected from the cervix to determine
whether they show signs of pre-neoplastic differentiation.
Cytologic screening programs have led to a large decline in
cervical cancer incidence and mortality in developed countries.
However, cervical cancer remains largely uncontrolled in high-
risk developing countries because of ineffective or no screening.9
Approximately 85% of new cases of cervical cancer (estimated
at 493,000 worldwide) and deaths from cervical cancer affect
women in developing countries each year.10
Cervical cytology, originally perceived useful in the detection
of pre-invasive disease and not just for identification of inva-
sive cervical cancer, came to be seen as a technique destined to
prevent cervical cancer.
In the 1960s, its use spread among developed countries;
meanwhile the concept that invasive squamous cell carcinoma
of the cervix arises from a spectrum of intraepithelial precursor
lesions appeared. This concept changed with the evolution of
scientific knowledge on the central role of human papilloma-
virus (HPV) in pathogenesis of cervical cancer and its precursor