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Interlaboratory agreement in assessment of gynaecological cytology in Cervical Cancer Screening Programme in Poland - a pilot evaluation

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Abstract

In our pilot study we have aimed to assess interlaboratory variability of cytological diagnoses in selected laboratories participating in the Polish Cervical Cancer Screening Programme (CCSP) to establish grounds for certification system for cytodiagnosticians and to monitor the quality of services. Set of 50 selected Pap smears, previously reassessed by an expert on the grounds of clinical, colposcopic and histological data was blinded and sent to 15 laboratories in Poland with request for evaluation according to routine practice according to the Bethesda 2001 system. Concordance with expert diagnoses reached a median of 82% (range: 66% to 92%), with median unweighted κ coefficient at κ = 0.67 (range 0.40 to 0.86) depending on laboratory. This indicates substantial agreement among laboratories, however with essential differences in proper evaluation in some outlying laboratories. Agreement was highest in samples with high-grade, lower for low-grade abnormalities. Slides with ASC-US and ASC-H expert diagnoses were most troubling for cytodiagnosticians. Sets of highly selected cytological slides with expert diagnoses may serve as a tool in the process of comprehensive periodic recertification of cytodiagnosticians in the screening programme. A benchmark level of agreement with expert diagnoses should be established to guide corrective actions for cytodiagnosticians with lowest agreement.
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Original paper
interlabOratOry agreement in assessment
Of gynaecOlOgical cy t O l O gy in cervical cancer
screening prOgramme in pOlanda pilOt eva luatiOn
Kin ga ZalewsKa-Otw i nO wsKa 1, anna Mac i Os 1,2, Katar Zy n a KOM er s Ka1, Ma łg O rZ ata re KO sZ 1,
and rZe j nO wa KOws Ki 1
1Department of Cancer Prevention, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
2Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education,
Warsaw, Poland
In our pilot study we have aimed to assess interlaboratory variability of cytolog-
ical diagnoses in selected laboratories participating in the Polish Cervical Cancer
Screening Programme (CCSP) to establish grounds for certification system for cyto-
diagnosticians and to monitor the quality of services. Set of 50 selected Pap smears,
previously reassessed by an expert on the grounds of clinical, colposcopic and his-
tological data was blinded and sent to 15 laboratories in Poland with request for
evaluation according to routine practice according to the Bethesda 2001 system.
Concordance with expert diagnoses reached a median of 82% (range: 66% to 92%),
with median unweighted κ coefficient at κ = 0.67 (range 0.40 to 0.86) depending
on laboratory. This indicates substantial agreement among laboratories, however
with essential differences in proper evaluation in some outlying laboratories.
Agreement was highest in samples with high-grade, lower for low-grade abnor-
malities. Slides with ASC-US and ASC-H expert diagnoses were most troubling for
cytodiagnosticians. Sets of highly selected cytological slides with expert diagnoses
may serve as a tool in the process of comprehensive periodic recertification of cyto-
diagnosticians in the screening programme. A benchmark level of agreement with
expert diagnoses should be established to guide corrective actions for cytodiagnos-
ticians with lowest agreement.
Key words: Pap test, cervical cancer screening, interlaboratory agreement, cyto-
diagnosticians.
dOi: https://dOi.Org/10.5114/pjp.2021.106445 pOl j pathOl 2021; 72 (1): 75-83
Introduction
Cervical cancer (CC) is the fourth most common
cancer and cancer-related cause of death in women
worldwide [1] and it is still an unsolved epidemio-
logical problem especially in low- and middle-income
countries [2]. In 2017 in Poland 2,502 new cases and
1,609 deaths due CC were reported by the Nation-
al Cancer Registry which translates into world-age
standardized incidence and mortality ratios in wom-
en of 7.7 and 4.2 per 100,000, respectively [3]. In
Poland, more than half of all CC cases occur among
women between 45 and 64 years old. Incidence and
mortality have been decreasing for the last few de-
cades in women under the age of 60 but these rates
are still stable in older women [4]. Also 5-years rel-
ative CC-related survival rates have remained un-
changed throughout last decade [5].
Screening for CC is recommended by Europe-
an Commission since 2003 as a form of secondary
76
Kinga ZalewsKa-OtwinOwsKa, anna MaciOs, KatarZyna KOMersKa, et al.
prevention [6] and has the potential to greatly re-
duce both CC incidence and mortality through early
identification of precancerous lesions which can be
treated far more effectively than in case of symp-
tomatic invasive disease [7]. In most of the devel-
oped countries which run organised/opportunistic
screening programmes, exfoliative cytology (PAP
test) is still the basic screening test. Even in countries
which switched to high risk human papillomavirus
(hr-HPV) test as a more sensitive screening method,
PAP tests are an integral part of triage algorithms
after a positive hr-HPV test [8, 9, 10, 11].
All types of cytological procedures are affected by
the problem of ambiguous results that hinder the im-
plementation of proper diagnostic and therapeutic
procedures. As a result of a multidisciplinary effort, in
1988 The Bethesda System (TBS) was developed in
order to create a standardized framework for cervical
cytology reports (including evaluation of specimen
adequacy, optional general categorization, descriptive
diagnosis) [12, 13].
TBS was accepted internationally. The system
was revised in 1991, 2001 and 2014 in reaction to
evolution of management and new research on cer-
vical cancer [13]. TBS for assessing abnormalities in
the cervix and in the thyroid gland was very readily
accepted by pathologists and clinicians, and the pre-
sented classifications created the foundation for a uni-
fied clinical procedure [12].
In 2006 in Poland, an organised CC screening
programme for women at the age between 25 and
59 was initiated. Pap test is offered every 3 years, in
accordance with the guidelines of the European Com-
mission and Polish Gynaecological Society [7, 14]. In
Poland, by law, cytopathologists (medical doctors
with specialty in pathology) and cytodiagnosticians
(laboratory diagnosticians with specialty in medical
cytomorphology) are entitled to assess cytological
samples. In OCCSP all Pap tests with abnormal re-
sults must be approved be a senior cytodiagnostician
or a cytopathologist. Results are coded according to
modified TBS 2001. Information about screening re-
sults is stored in an IT System for Prevention Mon-
itoring (pol. System Informatyczny Monitorowania
Profilaktyki, SIMP) and National Cancer Registry
(NCR) collects reports of cancer diagnosis. Algo-
rithms for abnormal results are set and include re-
peated testing and colposcopy/biopsy.
Apart from the coverage of target population by
the screening programme, quality assurance is a key
factor for obtaining full impact of screening on CC
epidemiology. Certification of laboratories and per-
sonnel is also important to maintain high quality
of cytological cervices. Evaluation of agreement be-
tween expert cytological diagnosis and laboratories/
cytodiagnosticians routinely working in CC screening
programmes may be one of the components of certi-
fication process. It may also be important for quality
assurance which plays a crucial role in cytology-based
CC screening [7]. In Poland quality assurance is led
by Central Coordination Centre (pol. COK Cen-
tralny Ośrodek Koordynujący). Although cytological
laboratories carrying out CC screening programme in
Poland undergo certification, to our knowledge inter-
laboratory agreement has never been evaluated and is
the subject of this pilot project.
Material and methods
In 2018 COK carried out a pilot study to assess
interlaboratory variability of cytological diagnoses in
selected laboratories operating in the Cervical Cancer
Screening Programme (CCSP). A set of 50 expert-se-
lected conventional cytology slides with clinical, col-
poscopic and histological confirmation of diagnoses,
collected in 2012-2015 was prepared. Slides original-
ly diagnosed by cytodiagnosticians of the Cytological
Laboratory of the Maria Sklodowska-Curie National
Research Institute of Oncology in Warsaw, Poland,
were reviewed again by an expert cytodiagnosti-
cian with 20 years of experience from the same lab.
The expert confirmed cytological diagnoses taking
into account clinical, colposcopic and histopatholo-
gy reports and selected smears formed a set repre-
sentative for each category of diagnoses according to
the Bethesda 2001 system (expert diagnoses are pre-
sented in Table I). The laboratory is high-through-
put, with internal quality-assurance and is co-oper-
ating with a Cervical Pathology Clinic performing
large-scale screening, colposcopic/histological triage
and treatment of women with cervical pathology also
within the CCSP.
The set with each-time blinded and mixed slides
was sent to 15 cytodiagnostic laboratories including
8 laboratories in Mazovian Voivodeship, 4 in Lublin
Voivodeship, 2 in Świętokrzyskie Voivodeship and
1 in Łódź Voivodeship, all operating in the CCSP.
Standard clinical data accompanied each slide. By
the decision of the head in each lab, a cytodiagnos-
tician or cytodiagnosticians were asked to evaluate
the set smears over a week along with routine every-
day practice. Each slide was to be assessed according
to the Bethesda 2001 system. After the evaluation
three types of coding were applied in COK to allow
for agreement analyses as follows:
Coding 1 (general): unsatisfactory for evaluation
vs normal (no intraepithelial lesion or malignan-
cy – NILM) vs. abnormal (atypical squamous
cells of undetermined significance [ASC-US] or
low-grade squamous intraepithelial lesion [LSIL]
or atypical squamous cells cannot exclude
HSIL [ASC-H] or high-grade squamous in-
traepithelial lesion [HSIL] or atypical glandular
cells [AGC] or squamous cell carcinoma [SCC]);
77
CerviCal CanCer SCreening Programme in Polanda Pilot evaluation
Table I. Experts’ and laboratories’ evaluations of prepared set of cytological slides with calculated percentage of laboratories coherent with experts in specific slide evaluation
blinded
slide
number
labOratOriesdiagnOses percentage Of labOratOries which
evaluated slides cOherently with
experts
majOrity
diagnOsis
experts
diag-
nOses
lab1lab2lab3lab4lab5lab6lab7lab8lab10 lab11 lab12 lab13 lab14 lab15 accOrding
tO detailed
cOding
accOrding
tO
aggregated
cOding
accOrding
tO general
cOding
1 USFE USFE NILM USFE USFE USFE USFE USFE USFE USFE USFE USFE USFE USFE USFE 85.7% 85.7% 85.7% USFE
2 USFE NILM NILM NILM NILM USFE NILM NILM NILM NILM NILM NILM NILM USFE NILM 14.3% 14.3% 14.3% NILM
3 USFE USFE NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 7.1% 7.1% 7.1% NILM
4 USFE NILM NILM NILM NILM NILM USFE NILM NILM USFE NILM NILM NILM NILM NILM 14.3% 14.3% 14.3% NILM
5 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
6 NILM NILM NILM NILM NILM NILM NILM NILM ASCUS NILM ASCUS NILM NILM NILM NILM 85.7% 85.7% 85.7% NILM
7 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
8 NILM ASCUS NILM NILM NILM ASCUS NILM NILM NILM NILM ASCUS NILM NILM NILM NILM 78.6% 78.6% 78.6% NILM
9 NILM NILM NILM NILM AGC NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 92.9% 92.9% 92.9% NILM
10 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
11 NILM NILM NILM NILM NILM NILM NILM NILM ASCUS ASCUS ASCUS NILM NILM NILM NILM 78.6% 78.6% 78.6% NILM
12 NILM NILM NILM AGC AGC NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 85.7% 85.7% 85.7% NILM
13 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
14 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
15 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
16 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
17 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
18 NILM NILM NILM NILM NILM NILM AGC NILM NILM NILM NILM NILM NILM NILM NILM 92.9% 92.9% 92.9% NILM
19 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
20 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
21 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
22 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
23 NILM NILM NILM NILM NILM USFE NILM NILM NILM NILM NILM NILM NILM NILM NILM 92.9% 92.9% 92.9% NILM
24 NILM NILM NILM NILM USFE NILM NILM NILM NILM NILM NILM NILM ASCUS NILM NILM 85.7% 85.7% 85.7% NILM
25 NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 100.0% 100.0% 100.0% NILM
78
Kinga ZalewsKa-OtwinOwsKa, anna MaciOs, KatarZyna KOMersKa, et al.
blinded
slide
number
labOratOriesdiagnOses percentage Of labOratOries which
evaluated slides cOherently with
experts
majOrity
diagnOsis
experts
diag-
nOses
lab1lab2lab3lab4lab5lab6lab7lab8lab10 lab11 lab12 lab13 lab14 lab15 accOrding
tO detailed
cOding
accOrding
tO
aggregated
cOding
accOrding
tO general
cOding
26 NILM NILM NILM NILM NILM NILM NILM NILM AGC NILM NILM NILM NILM NILM NILM 92.9% 92.9% 92.9% NILM
27 ASCUS ASCUS NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM NILM 7.1% 7.1% 7.1% NILM
28 ASCUS ASCUS ASCUS ASCUS NILM NILM NILM ASCUS ASCUS ASCUS ASCUS NILM ASCUS NILM NILM 57.1% 57.1% 57.1% ASCUS
29 ASCUS HSIL HSIL AGC NILM ASCH ASCH ASCH HSIL HSIL HSIL ASCH HSIL HSIL NILM 0.0% 0.0% 85.7% HSIL
30 ASCUS LSIL ASCUS NILM NILM ASCUS NILM NILM LSIL NILM ASCUS NILM LSIL NILM NILM 21.4% 42.9% 42.9% NILM
31 ASCUS HSIL ASCH ASCUS NILM ASCUS NILM NILM ASCH ASCH HSIL HSIL HSIL HSIL ASCUS 21.4% 21.4% 78.6% HSIL
32 ASCUS ASCUS ASCUS NILM NILM USFE NILM NILM NILM NILM ASCUS NILM LSIL NILM NILM 21.4% 28.6% 35.7% NILM
33 ASCH ASCH LSIL ASCUS NILM NILM NILM NILM ASCH ASCUS ASCH ASCH ASCH ASCUS ASCUS 35.7% 35.7% 71.4% ASCH
34 ASCH ASCH ASCH NILM NILM NILM NILM NILM ASCH ASCUS ASCH ASCH ASCH LSIL ASCUS 42.9% 42.9% 64.3% ASCH
35 ASCH NILM NILM NILM ASCUS NILM NILM NILM HSIL ASCUS ASCH NILM ASCUS NILM ASCUS 7.1% 7.1% 42.9% NILM
36 LSIL LSIL ASCUS ASCUS LSIL LSIL ASCUS LSIL ASCUS LSIL ASCH LSIL LSIL LSIL ASCUS 57.1% 100.0% 100.0% LSIL
37 LSIL LSIL LSIL ASCUS LSIL LSIL NILM ASCUS ASCUS LSIL ASCH LSIL LSIL LSIL ASCUS 57.1% 92.9% 92.9% LSIL
38 LSIL LSIL LSIL LSIL LSIL LSIL NILM LSIL ASCH LSIL ASCH LSIL LSIL ASCUS NILM 64.3% 71.4% 85.7% LSIL
39 LSIL HSIL ASCH LSIL LSIL ASCUS ASCH LSIL ASCH ASCH HSIL LSIL HSIL LSIL ASCUS 35.7% 50.0% 100.0% LSIL
40 LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL 100.0% 100.0% 100.0% LSIL
41 LSIL ASCUS ASCUS NILM NILM NILM NILM NILM NILM ASCUS NILM NILM ASCUS NILM NILM 0.0% 28.6% 28.6% NILM
42 LSIL LSIL LSIL ASCUS LSIL ASCUS NILM NILM LSIL LSIL LSIL ASCUS LSIL LSIL LSIL 64.3% 85.7% 85.7% LSIL
43 HSIL HSIL HSIL ASCUS HSIL HSIL ASCH LSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL 78.6% 85.7% 100.0% HSIL
44 HSIL HSIL HSIL ASCH ASCUS HSIL HSIL ASCUS AGC HSIL ASCH HSIL HSIL HSIL ASCUS 57.1% 78.6% 100.0% HSIL
45 HSIL HSIL ASCH AGC HSIL HSIL AGC HSIL HSIL HSIL HSIL HSIL AGC HSIL HSIL 71.4% 100.0% 100.0% HSIL
46 HSIL HSIL HSIL ASCH NILM NILM HSIL NILM HSIL ASCH ASCH ASCH HSIL ASCH ASCUS 35.7% 71.4% 78.6% HSIL
47 HSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL HSIL 100.0% 100.0% 100.0% HSIL
48 HSIL LSIL ASCH LSIL LSIL LSIL ASCUS LSIL LSIL LSIL LSIL LSIL HSIL LSIL LSIL 7.1% 7.1% 100.0% LSIL
49 HSIL HSIL HSIL LSIL HSIL HSIL HSIL LSIL HSIL HSIL HSIL HSIL HSIL HSIL ASCH 78.6% 85.7% 100.0% HSIL
50 SCC SCC SCC ASCH NILM ASCH ASCH SCC SCC SCC SCC HSIL SCC SCC NILM 57.1% 85.7% 85.7% SCC
Table I. Cont.
79
CerviCal CanCer SCreening Programme in Polanda Pilot evaluation
Table II. Consistency of experts’ and laboratories evaluations according to general, aggregated and detailed coding
experts
diagnOses
number
Of
slides
prepared
fOr the
study
cytOdiagnOsticiansdiagnOses, n (%)
general cOding aggregated cOding detailed cOding
cOherent
with
experts
diagnOsis
incOherent with experts
diagnOsis
cOherent
with
experts
diagnOsis
incOherent with experts
diagnOsis
cOherent
with
experts
diagnOsis
incOherent with experts
diagnOsis
Overall under-
stated
Over-
stated
usfe Overall under-
stated
Over-
stated
usfe Overall under-
stated
Over-
stated
usfe
USFE 4 18
(32.1)
38
(67.9)
. . . 18
(32.1)
38
(67.9)
. . . 18
(32.1)
38
(67.9)
. . .
NILM 22 291
(94.8)
14
(4.6)
. 14
(4.6)
2
(0.7)
291
(94.8)
14
(4.6)
. 14
(4.6)
2
(0.7)
291
(94.8)
14
(4.6)
. 14
(4.6)
2
(0.7)
ASC-US 6 42
(50.0)
41
(48.8)
41
(48.8)
. 1
(1.2)
22
(26.2)
61
(72.6)
41
(48.8)
20
(23.8)
1
(1.2)
18
(21.4)
65
(77.4)
41
(48.8)
24
(28.6)
1
(1.2)
LSIL 7 83
(84.7)
15
(15.3)
15
(15.3)
. 0
(0.0)
72
(73.5)
26
(26.5)
15
(15.3)
11
(11.1)
0
(0.0)
53
(54.1)
45
(45.9)
34
(34.7)
11
(11.1)
0
(0.0)
ASC-H 3 25
(59.5)
17
(40.5)
17
(40.5)
. 0
(0.0)
13
(31.0)
29
(69.0)
29
(69.0)
. 0
(0.0)
12
(28.6)
30
(71.4)
29
(69.0)
1
(2.4)
0
(0.0)
HSIL 7 95
(96.9)
3
(3.1)
3
(3.1)
. 0
(0.0)
75
(76.5)
23
(23.5)
23
(23.5)
. 0
(0.0)
60
(61.2)
38
(38.8)
38
(38.8)
0
(0.0)
0
(0.0)
SCC 1 11
(78.6)
3
(21.4)
3
(21.4)
. 0
(0.0)
11
(78.6)
3
(21.4)
3
(21.4)
. 0
(0.0)
7
(50.0)
7
(50.0)
7
(50.0)
0
(0.0)
0
(0.0)
Low-
grade
lesions
13 125
(68.7)
56
(30.8)
56
(30.8)
. 1
(0.5)
94
(51.6)
87
(47.8)
56
(30.8)
31
(17.0)
1
(0.5)
71
(39.0)
110
(60.4)
75
(41.2)
35
(19.2)
1
(0.5)
High-
grade
lesions
11 131
(85.1)
23
(14.9)
23
(14.9)
. 0
(0.0)
99
(64.3)
55
(35.7)
55
(35.7)
. 0
(0.0)
79
(51.3)
75
(48.7)
74
(48.1)
1
(0.6)
0
(0.0)
Abnormal 24 256
(76.2)
79
(23.5)
79
(23.5)
. 1
(0.3)
193
(57.4)
142
(42.3)
111
(33)
31
(9.2)
1
(0.3)
150
(44.6)
185
(55.1)
149
(44.3)
36
(10.7)
1
(0.3)
USFE – unsatisfactory for evaluation; NILM – no intraepithelial lesions or malignancy; ASC-US – atypical squamous cells of undetermined significance; LSIL – low grade squamous intraepithelial lesions; ASC-H – atypical squamous cells –
cannot exclude HSIL; HSIL – high grade intraepithelial lesions; SCC – squamous cell carcinoma; low-grade lesions include ASC-US and LSIL; high-grade lesions include ASC-H, HSIL and SCC; abnormal results include diagnoses ASC-US
and more severe
80
Kinga ZalewsKa-OtwinOwsKa, anna MaciOs, KatarZyna KOMersKa, et al.
Coding 2 (aggregated): unsatisfactory for evaluation
vs. normal (NILM) vs. low-grade lesions (LSIL or
ASC-US) vs. high-grade lesions (ASC-H or HSIL
or AGC or SCC);
Coding 3 (detailed): unsatisfactory for evaluation
vs. normal (NILM) vs. ASC-US vs. LSIL vs.
ASC-H vs. AGC vs. HSIL vs. SCC.
The study followed the Declaration of Helsin-
ki and the protocol was approved by the Ministry
of Health.
Statistical analysis
Percentages of laboratories’ diagnoses coherent
with expert’s evaluations were calculated in each type
of coding. Unweighted Cohen’s κ statistics were es-
timated for laboratories participating in pilot study.
Weighted (κw) κ were also computed since unweight-
ed κ does not account for severity of the diagnoses.
Weights were adjusted so that unsatisfactory for eval-
uation diagnosis was considered as in total disagree-
ment with any distinct diagnosis and other diagnoses
were squarely weighted. Level of <0.05 was estab-
lished as significant. Landis and Koch’s approach was
applied to interpret agreement expressed by κ coef-
ficients as: < 0 – poor; 0.0-0.2 – slight; 0.2-0.4
fair; 0.4-0.6 moderate; 0.6-0.8 substantial and
0.8-1.0 – almost perfect. Stata 15 software [15] was
used for statistical analyses.
Results
Of 15 diagnostic centres involved in study, 13 labs
evaluated all of the 50 prepared slides, 1 lab evaluat-
ed 49 smears and 1 lab – only 29 slides. Since the dis-
tribution of normal and abnormal slides in the set
evaluated by last laboratory was not coherent with
the distribution of set of all 50 smears, this labora-
tory was excluded from further analysis (Table I: full
source data with expert’s and laboratories’ diagno-
ses). Total number of 728 readings was collected and
699 of them were analysed: 21 considered as unsatis-
factory for evaluation and 678 as adequate. However,
only 32.1% of truly unsatisfactory for evaluation as-
sessments were recognized correctly (Table II). Slides
originally assessed as adequate for evaluation were
recognized properly in 99.5%.
Cytodiagnosticians managed to evaluate correctly
94.8% of normal smears overall (range from 86.4%
to 100% by lab) and recognized correctly 76.2%
of abnormal slides (range from 50% to 95.8% by
lab). Of 336 slides with expert’s diagnosis of “pres-
ence of abnormal cells”, 79 were apprised as normal
(23.5%). On the other hand, 14 of 307 expert’s “nor-
mal (no intraepithelial lesion or malignancy) readings
were identified as abnormal (4.6%). The vast major-
ity of slides assessed originally as “unsatisfactory for
evaluation” by the expert (38 of 56) were diagnosed
as normal (67.9%).
High-grade lesions were correctly recognized
more often than low-grade ones (64.3% vs. 51.6%).
Slides with ASC-US or LSIL were considered as nor-
mal rather than high-grade (56 readings vs. 31 read-
ings, 30.8% vs. 17.0%).
Of 8 categories in detailed coding, smears with
ASC-US and ASC-H expert’s diagnoses were evalu-
ated discordant by cytodiagnosticians most frequent-
ly (21.4% and 28.6% of coherent diagnoses, respec-
tively). Of 14 squamous cell carcinoma readings in
laboratories undergoing assessment, in 3 the cases
were apprised as normal (21.4%). Among 408 slides
considered as normal by laboratories, 11 were misdi-
A
B
Fig. 1. Percentage of concordant diagnoses in (A) general,
(B) aggregated, (C) detailed coding by laboratory. Vertical
line indicates median percentage of correct diagnoses by
lab in specific coding
1
13
10
2
14
11
12
8
3
15
5
7
6
4
Number of laboratory
50 55 60 65 70 75 80 85 90 95
1
13
2
12
14
10
8
5
11
3
15
6
7
4
Number of laboratory
50 55 60 65 70 75 80 85 90 95
C
1
13
2
14
12
10
11
5
8
7
4
15
6
1
Number of laboratory
50 55 60 65 70 75 80 85 90 95
Percentage of concordant diagnoses
92
90
88
88
84
84
82
82
80
78
76
72
70
66
84
82
80
76
74
74
72
71
70
70
66
64
62
60
80
74
72
70
70
70
66
65
62
60
60
58
56
56
81
CerviCal CanCer SCreening Programme in Polanda Pilot evaluation
agnosed (79 of them (19.4%) was abnormal accord-
ing to expert’s opinion).
The proportion of correct diagnoses, weighted and
unweighted κ coefficients were estimated for each
laboratory. The median percentage was calculated as
82% (range 66-92%) in general coding, 72% (range
60-84%) in aggregated coding and 66% (range
56-80%) in detailed coding (Fig. 1). Unweighted
κ coefficients among labs ranged from 0.40 to 0.86
for general coding, from 0.37 to 0.76 for aggregated
coding and from 0.34 to 0.73 for detailed coding and
median unweighted κ coefficients correspond with
substantial (0.67), moderate (0.59) and moderate
agreement (0.53), respectively (Table III).
Weighted κ coefficients were calculated to account
for differences in severity of diagnoses. In the detailed
coding κw ranged from 0.40 to 0.76 with median
of 0.65, identifying substantial agreement.
Each slide was assigned to percentage of diag-
nostic centres which diagnosed it correctly by each
type of coding (Table II). Of 50 smears, 35 (70%)
were recognized correctly by more than 80% of lab-
oratories in general coding, 30 (60%) in aggregated
coding and 23 (46%) in detailed coding. However,
4 slides (8%) were properly evaluated by at most
20% of diagnostic centres in general, 7 (14%) in ag-
gregated and 8 (16%) in detailed coding. Two slides
were identified incorrectly by all of the laboratories
in detailed and one on them also in aggregated cod-
ing. Expert diagnosed one of these slides as LSIL and
one as ASC-US. Most of smears with more than 80%
proper identifications were normal ones [22]. Over-
all, each slide was recognized properly by average
of 81.0% laboratories in general, 71.9% in aggre-
gated and 65.7% in detailed coding (median 92.9%,
85.7% and 78.6%, respectively).
Discussion
Cytological laboratories participating in the na-
tional population-based cervical cancer screening
programmes should be certified and subject to both
internal and external quality assurance [7]. Internal
quality assurance include re-screening of slides, mon-
itoring primary screening detection rates, assessment
of cyto-histologic, cyto-clinical, cyto-virological cor-
relations and audit of interval cancers according to
EU Guidelines [7]. External quality assurance is less
defined, varies between countries and may include
proficiency testing and comparison of laboratory and
personal reporting rates with set national standards
(p. 167 in [7]).
Although cervical cytology is commonly used
world-wide in developed countries, its accuracy in
detection of cervical neoplasia may vary greatly since
it is a very subjective method [14, 16] and diagnoses
may differ from lab to lab [17]. Some studies show
only fair agreement (with κ < 0.3) between cytodi-
agnosticians evaluating cytology samples [18]. Low
grade abnormalities causes most troubles in estab-
lishing correct diagnosis [19].
In this study we have aimed to develop grounds
for future periodic proficiency testing in assessment
of cytological slides and run a pilot evaluation of se-
lected cytodiagnosticians operating in cervical cancer
screening programme in Poland. These activities are
a part of effort to form a certification/periodic recer-
tification process. We have also aimed to assess inter-
laboratory agreement in assessment of a set of highly
selected cytological slides representing a wide spec-
trum of normal and abnormal conditions of the uter-
ine cervix. Although the CCSP in Poland has been
in place since 2006/2007 such activities have been
attempted for the first time.
In general, we have found average to very high
agreement between the original expert cytological
diagnosis and diagnosis reached by laboratories par-
ticipating in our pilot project. Interpretation of Pap
smears is subjective so achieved concordance with ex-
pert diagnoses of each slide by average of 81.0% lab-
oratories in general, 71.9% in aggregated and 65.7%
in detailed coding is a fairly good result.
One laboratory (number 1) had repeatedly high-
est agreement rate in all three types of coding. On
the other hand, another laboratory (number 4) had
the lowest agreement rate in two types (general, ag-
gregated) coding of diagnoses according the Bethesda
system. This may indicate that quality of assessment
may differ between cytological laboratories partici-
pating in national screening and reasons for high dis-
agreement in outlying laboratories should be sought.
Our results show that cytodiagnosticians found
proper classification of unsatisfactory for evaluation
slides from normal slides troubling. Only 32.1%
of slides with original expert diagnosis of “unsatisfac-
tory for evaluation” were recognized correctly. This
should be taken under consideration in future ver-
ification of cytological diagnoses and more impact
Table III. Agreement among laboratories. Median and
range was calculated for percentage of agreement, weight-
ed and unweighted κ coefficients
type
Of cOding
cOefficient Of agreement, median
(range)
percentage
[%]
κ cOefficient
unweighted weighted
General 82
(66-92)
0.67
(0.40-0.86)
0.67
(0.40-0.86)
Aggregated 72
(60-84)
0.59
(0.37-0.76)
0.69
(0.36-0.79)
Detailed 66
(56-80)
0.53
(0.34-0.73)
0.65
(0.40-0.76)
82
Kinga ZalewsKa-OtwinOwsKa, anna MaciOs, KatarZyna KOMersKa, et al.
should be place on the smear quality during the pro-
cess of training of cytodiagnosticians in Poland.
Percentage of slides correctly diagnosed as abnor-
mal was 76.2%, however, results strongly vary be-
tween specific diagnoses from 21.4% slides correctly
diagnosed as ASC-US to 61.2% slides correctly diag-
nosed as HSIL. Some of previous studies show that
the greatest source of disagreement in cytology re-
sults involved interpretation of low-grade lesions [20,
21, 22] and our study seems to be in agreement with
these findings. The number of recognized abnormal
slides varied from 50% to 95.8% by laboratory which
suggests great differences in reporting between some
of them and should trigger corrective measures in
labs with low detection rates which directly influence
the quality of the whole screening process.
Slides were evaluated additionally to normal
workload in laboratories, so it may have influenced
the results. Other limitation of our pilot study is
the limited number of laboratories which took part
in our project. However we have initiated actions to
run similar analyses for each cytodiagnostician partic-
ipating in the CCSP in Poland and make it a future
requirement of certification and periodic recertifica-
tion.
COK as part of Department of Cancer Prevention,
The Maria Sklodowska-Curie National Research In-
stitute of Oncology, Warsaw, Poland, on the basis
of the agreement made with the Ministry of Health
is obliged, among other responsibilities, to monitor
the quality of services provided by laboratories par-
ticipating in the CCSP. We have carried out this study
to evaluate consistency of cytological diagnoses in se-
lected laboratories in Poland. The results of the pilot
study will lead to the development of methods for
evaluation laboratories in the CCSP and therefore to
ensure the high quality cytological diagnoses. Period-
ic skills evaluation system is planned to be introduced
to certify cytologists working in the CCSP.
The analysis carried out on the basis of the data
collected during the pilot study clearly indicates
the necessity of conducting further verification
of the consistency in cytological diagnoses. External
audits should be run systematically and also include
monitoring of colposcopy examinations, histopatho-
logical results and effectiveness of treatment and
COK initiated actions and is working to imple-
mented these monitoring activities into the CCSP
in Poland.
The authors declare no conflict of interest.
The study was financed by the Polish Ministry of Health
through the National Cancer Control Programme with-
in the objective of coordination and monitoring of quality
of cervical and breast cancer screening.
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Address for correspondence
Kinga Zalewska-Otwinowska
Maria Sklodowska-Curie National Research Institute of Oncology
Department of Cancer Prevention
Roentgen 5
02-781 Warsaw, Poland
tel./fax: +48 22 546 30 21
e-mail: kinga.zalewska-otwinowska@pib-nio.pl
ResearchGate has not been able to resolve any citations for this publication.
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Objective: One of the problems encountered when assessing cervical precancerous lesions is intra- and interobserver variability. The aim of this study was to determine the degree of interobserver variation in conventional PAP smears (CPS) and liquid-based cytology (LBC). Materials and Methods: The diagnostic variability among three pathologists was assessed using 120 smears (67 conventional CPS and 53 LBC). The cases were selected retrospectively from the archives of the Pathology Department among the patients with follow-up, such as biopsy confirmation and/or persistent/ resolving disease in the follow-up smear. The observers examined the slides in a blinded fashion. Results: Diagnostic agreement on the presence or absence of intraepithelial lesions was found in 30 of 51 slides (58.82%) of LBC (kappa=0.42) and in 44 of 67 slides (65.67%) of conventional cytology (kappa=0.50). The agreement was slightly higher in conventional smears. The highest agreement was in the LSIL category with a kappa value of 0.50 in LBC and 0.62 in conventional cytology, while ASCUS was the least reproducible diagnosis. Conclusion: Our results are in agreement with the literature in that the reproducibility of cervical cytology shows low to moderate consistency. The study showed no significant difference between LBC and CPS in the reproducibility of the diagnosis.