Cytologic Screening Programs
Fig. 3.2
Incidence and mortality rates of
cervical cancer in the Nordic countries,
1958-97 (mortality available up to 1996).
Whole female population, adjusted for
age to the world standard population
(Laara et al. (1987); Engeland et al. (1993);
Hristova and Hakama (1997); Parkin et
al. (1997); Moller et al. (2002); EUROCIM
(European Network of Cancer Registries)
database).21,74-77 Reproduced with permission
of IARC— International Agency for Research
on Cancer.12
woman apparently not affected from the woman who could
have the disease.
Even though the efficacy of cytology screening has never been
proven through randomized trials, it is generally agreed that the
marked reduction in the incidence and mortality from cervical
cancer before and after the introduction of screening programs
in a variety of developed countries has been interpreted as strong
non-experimental support for organized cervical cancer screen-
ing programs.17,18
The best known studies are those that compare incidence
and mortality in Iceland and in the four Nordic countries19-21
(Fig. 3.2). Before screening was installed in Iceland, mortality
had been on the increase but fell 50% in the period of 10 years
from introducing screening. In the Nordic countries, the decline
in cumulative incidence rates over a 15-year period, between
1966-70 and 1981-5, was related to the coverage and extent of
the organized programs. In Norway, where only 5% of the pop-
ulation had been screened opportunistically, the incidence rates
fell by 20% in comparison to Finland, with a national popula-
tion-based program, where incidence fell by 65%.
In a study of invasive cervical cancer in British Columbia,
approximately half of the new cases diagnosed had no previous
cytology or the last examination had been made more than 5
years ago.22
Two important parameters traditionally used to measure the
validity of screening tests are sensitivity and the specificity. The
sensitivity means the percentage of positive cases reported as
being positive. It relates to the ability of disease detection and it
can be calculated using the formula
Sensitivity =
x 100%
true-positive + false-negative
The specificity means the percentage of negative cases reported
as being negative. It relates to the ability of disease exclusion
and it can be calculated using the formula
Specificity =
x 100%
true-negative + false-positive
A third criterion is the positive predictive value that measures
the probability of the disease to be present in the patients whose
test was reported as positive, and it can be calculated using the
Positive predictive value
----------------------------------------x 100%
true- positive + false-p ositive
Glandular lesions are much less frequent than those origi-
nating from squamous epithelium and the diagnosis of the
intraepithelial forms is the principal objective of the screening
programs. In relation to the prevention of cervical adenocarci-
noma, the Papanicolaou test is potentially a powerful weapon,
but in comparison to the diagnosis of squamous lesions, the
diagnosis of cervical adenocarcinoma in situ has shown a sig-
nificantly higher rate of false-negatives, not being so effective in
the prevention of invasive glandular lesions.23
In 2004 a working group at the International Agency for
Research on Cancer (IARC) of the World Health Organization
(WHO) met to evaluate the efficacy of prevention of cervical
cancer in reducing mortality caused by the disease. They con-
cluded that the programs of prevention based on the Papanico-
laou test continue being the mainstay for prevention of this type
of cancer throughout the world, there being sufficient evidence
that screening of cervical cancer diminishes mortality caused by
the disease.24
Despite the knowledge of the efficacy of cytopathologic tests
in contributing to the reduction of cervical cancer through organ-
ized programs by their characteristics of simplicity, acceptability,
and low cost, studies have shown major variations in the esti-
mates of sensitivity and specificity of the test. A meta-analysis
to estimate the accuracy of the Pap test in which data from 59
studies were combined reported estimates of sensitivity and
specificity ranging from 11 to 99% and 14 to 97%, respectively.25
A systematic review reported sensitivity and specificity ranging
from 30 to 87% and 86 to 100%, respectively.26
Sensitivity and specificity are important parameters for the
evaluation of the accuracy of the screening test. However, it is
important to bear in mind that the efficacy of screening is not
restricted to the performance of the test used. Special empha-
sis must be given to the need to develop organized programs
that have a systemic approach, that are well integrated into the
existing health system, and which consider social, cultural, and
economic aspects. A meta-analysis of social inequality and the
risk of cervical cancer in 57 studies revealed that both cervical
infection with HPV and a lack of access to adequate cervical can-
cer screening and treatment services are likely to be important in
explaining the large cervical cancer incidence rates observed in
different socioeconomic groups.27 An estimated 100% increased
risk of invasive cervical cancer was found for women in low
social class categories when compared with women in high
social class categories.
In an analogous way, this difference occurs in developing
countries and those developed where the inequality in the
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