Cervical Cancer Screening and Human Papillomavirus (HPV ... - KCE

6 Cervical cancer screening and HPV KCE reports vol.38
2.2 ASSESSMENT OF THE PERFORMANCE OF SCREENING
TESTS
The aim of cervical cancer screening is to detect progressive cervical intra-epithelial
neoplasia (CIN 1 ) and, by their treatment, prevent progression to invasive cancer 4 .
The effectiveness of a screening programme is determined by the programme
sensitivity. This programme sensitivity depends on the sensitivity of the chosen
screening test for CIN of a given degree, the natural history of this degree of CIN, and
the screening policy (the target age group, screening interval, and procedures for
follow-up of positive screenees). The essential elements in the natural evolution of the
disease are the rates of onset, progression and regression of precursor lesions and the
distribution of their sojourn times. The mean sojourn time of CIN is at least 10 years
and the probability of detection increases as the preclinical phase progresses 5, 6 .
Therefore, repetition of a moderately sensitive screen test, such as the Pap smear can
reduce incidence of and mortality from cervical cancer to a low residual level 7 . The
reduction in the cumulative incidence of cancer is estimated to be respectively 91 and
84% due to well organised cytological screening every 3 or 5 years 8, 6 .
The success of screening depends essentially on the participation of the target
population and the quality of the screening test and further on the compliance and
efficacy of treatment of screen-detected lesions.
In this chapter we focus on the performance of screening methods. We will describe
and assess the performance of 5 main types of tests that are currently used in cervical
cancer screening in Europe or that are proposed as an alternative or supplement for
current methods:
The conventional Pap smear
Liquid based cytology
Automated cytology
Colposcopy
Detection of nucleic acid sequences of oncogenic Human papilloma viruses
For an overview of principles of good diagnostic research to evaluate test accuracy, we
refer to The Cochrane Methods Group on Systematic Review of Screening and
Diagnostic Tests: Recommended Methods 9 and Bossuyt 10 .
Classifications
The 1988 version of The Bethesda Reporting System (TBS) was used for the cytological
classification of the test result 11 . We considered three threshold levels for positive
cytology: atypical squamous cells of undetermined significance or worse (ASCUS+),
low-grade squamous intra-epithelial lesions or worse (LSIL+) and high-grade intraepithelial
lesions or worse (HSIL+). Atypical glandular lesions were assimilated together
within the ASCUS category. Categories of cytological abnormality, defined according to
other reporting formats, were converted into TBS using translation tables as established
before 1 . At the 1991 Bethesda Workshop, it was proposed to sub-classify ASCUS
into three sub-classes: "atypical squamous cells favouring a benign reactive process"
(ASC-R), "atypical squamous cells of undetermined significance" (ASC-US) and ASC-H,
"atypical squamous cells, HSIL cannot be ruled out" 12 . At the 2001 Workshop, it was
decided to integrate henceforth ASC-R into the group of "negative for intraepithelial
lesion or malignancy" and to distinguish only "ASC-US" (with hyphen) and "ASC-H"
(Solomon 2002). In our main meta-analyses, we accepted studies using TBS2001 and
providing data for equivocal cytology, if they included ASC-US (alone) or ASC-US and
ASC-H (combined). Studies considering ASC-H alone or atypical glandular cells alone
were excluded.
1 In this chapter CIN (cervical intra-epithelial neoplasia) is used for histologically confirmed lesions,
while the SIL (Bethesda) terminology is used to describe cytological findings.