Introduction
If detected early, cervical cancer is almost entirely avoidable and curable. The Papanicolaou
smear (Pap smear) is the first precautionary screening procedure and has been used
in Germany since 1971 as part of a statutory opportunistic cancer screening program
(CS program) [1 ]
[2 ]. The incidence and mortality for cervical cancer has decreased significantly since
the introduction of this CS procedure [3 ].
The organized cancer screen program (oKFE) now used in Germany was introduced as a
consequence of some historical decisions. In January 2019, the Federal Research Ministry
of Germany (Bundesforschungsministerium , BMBF) initiated a National Decade Against Cancer (NDC) as a countermeasure against
the predicted continuous increase in the number of new cases with cancer in Germany
[4 ]. This resulted in changes to the previous process used for the early detection of
cervical cancer in Germany, as it was felt that further action was still needed despite
the drop in the number of new cases with cervical cancer [5 ]. Every year, just under 4500 women are still diagnosed with cervical cancer in Germany
(Center for Cancer Registry Data, as at 2022) [6 ]. Since 2020, an organized cancer screening program (oKFE) has been
implemented in Germany, based on the relevant directive issued by the Federal Joint
Committee (Gemeinsamer Bundesausschuss , G-BA) [5 ]. The directive defines the invitation process, the examination methods, the intervals
between examinations, the algorithms used to evaluate findings as well as processes
for quality assurance, evaluation and safety of the program. Gesundheitsforen Leipzig
GmbH was commissioned by the G-BA to be the independent review office which would
accept, manage and evaluate the data collected in the context of the program.
Screening is generally carried out in people who probably do not have cancer. False-positive
findings which then involve further examinations to clarify the results are associated
with high levels of emotional stress until the final result is available [7 ]
[8 ]. But the risks of the examination methods themselves must also be carefully weighed
up against the desired benefit [9 ]. For this reason, a detailed evaluation report is compiled every two years for the
G-BA. The report provides a continuous assessment of the program and suggests necessary
optimizations [5 ]
[10 ]. The report focuses on the questions specified in the directive regarding the acceptance
of screening, its implementation, and the results of the
different examinations. The existing framework conditions for screening such as the
target population, data sources, analyzed parameters, and the validation of data are
described in detail [10 ].
The first evaluation report on the cervical cancer screening program was published
in May 2024 [10 ]. The report covers the data years 2021 and 2022 and represents an important milestone
since the introduction of organized cancer screening.
This paper analyzes the first Germany-wide results of primary screening presented
in the evaluation report. The existing limitations with regards to the collection
and evaluation of data have been considered. This publication has three main goals.
It aims to provide a concise overview of the comprehensive results obtained with both
screening methods in the context of the organized cancer screening program for the
early detection of cervical cancer: cytology-based primary screening (PSZ) of eligible
women aged 20–34 years and primary screening combined with co-testing (PSK) of eligible
women aged 35 years and above. It also aims to identify initial trends and key findings
in the collected data and to attempt, based on these results, to provide a perspective
for future developments and possible implications with regards to cervical cancer
screening.
Material and Methods
Legal basis for data collection
The legal basis for the Directive for Organized Cancer Screening Programs (Richtlinie für organisierte Krebsfrüherkennungsprogramme , oKFE-RL) was included in the German Social Security Code (SGB) in the form of Sec. 25a
of Book V of the SGB. It was based on the law on the development of cancer screening
and quality assurance and the use of clinical cancer registries (the Cancer Screening
and Registries Act [Krebsfrüherkennungs- und -registergesetz {KFRG}] of 09.04.2013) [11 ]. The purpose was to address key recommendations of the German National Cancer Plan
regarding the further development of cancer screening and to prepare the way for their
implementation [12 ]. The organized cancer screening program for the detection of cervical cancer, which
is based on the directive, started on January 1st, 2020 [5 ].
Database
The results of the primary screening carried out in the context of the organized cancer
screening program presented here are from a database which uses two data sources.
The first source are data from statutory health insurance companies which collect
and store data in accordance with Sec. 284 para. 1 of the SGB V. This source also
includes data from the facilities which issue invitations to attend screening. The
data includes the insurance numbers of insured women (Sec. 290 of the SGB V), the
date of issuing the invitation, the date of birth, the date of death, and possibly
the date of any objections raised against being invited for screening. This data is
then combined with data from the second source, which consists of data from service
providers which has been pseudonymized. The data from service providers offers information
about and results for the examinations carried out by gynecologists as well as the
findings of the cytology laboratories. The third data source
required by the oKFE Directive is data from the clinical cancer registries of the
German federal states. This third source had not yet been linked to the other two
at the time of compiling the results for the evaluation report and will only be available
for assessment in the next evaluation report. For the period from 1 January 2020 to
30 September 2020, the documentation obligation was suspended following a decision
of the G-BA which was approved by the German Ministry of Health (Bundesministerium für Gesundheit , BMG) [13 ]. This means that for 2020, only data from the 4th quarter is available, making it
impossible to provide a detailed look at the first data year of this newly initiated
program. The data described in the following pages covers the data years 2021 and
2022. To ensure that the data in the database can be evaluated and is valid, data
transfers from the above described data sources are carried out in
accordance with binding specifications. The professional and technical specifications
for the transfer of data used to evaluate the program in accordance with the oKFE-RL
are developed by the Institute for Quality Assurance and Transparency in Healthcare
(IQTIG). IQTIG was commissioned to develop them by the G-BA and they are published
annually [14 ]
[15 ]. How relevant data of the primary screening examinations is collected and transferred
is specified by IQTIG. The data obtained using the screening methods specified by
the oKFE-RL are recorded using documentation forms which are defined in the annual
specifications of IQTIG [14 ]
[15 ].
Population
In accordance with the oKFE-RL, two cancer screening methods for primary screening
are used to identify suspicious changes, cancers, and precancerous lesions. The aim
is to detect and treat lesions as early and as best as possible [10 ]
[16 ]. The entitlement to primary screening depends on the age of the woman [10 ]
[16 ]. Women entitled to have screening examinations in accordance with the oKFE include
all women insured by statutory healthcare companies (GKV) above the age of 20 years.
This publication only reviews results obtained from primary screening examinations.
The investigated population is divided into two age groups in accordance with the
requirements of the oKFE Directive. For the group aged from 20 to 34 years, the results
of cytology-based primary
screening (PSZ) are reviewed, with all persons in this group entitled to have annual
screening. For the group aged 35 years and above, the results of primary screening
with co-testing (PSK) are reviewed, with all persons in this group entitled to have
screening every three years. The test results for this group also include the results
of HPV testing in addition to the findings of the Pap test [10 ]
[16 ].
Parameters
For this evaluation, the following parameters collected during primary screening examinations
are presented descriptively: cytology results classified using the Munich Nomenclature
III (MNK III) [17 ]; the results of HPV testing; the vaccination status. Data processing, the creation
of tables, and the graphic representations of results were carried out using programming
language R [18 ], Version 4.4.1. All graphics in the Results and Discussion chapters were created with ggplot2 [19 ].
Depending on the specific question, the analysis of results uses either data from
the insurance companies or data from the type of examination.
Results
The presented results were obtained from the comprehensive evaluation report on the
organized cancer screening program for cervical cancer provided by the independent
oKFE review office in 2023.
To evaluate the program, the oKFE-RL defined questions which could be answered using
the collected data [16 ]. This Results chapter examines a few selected aspects which focus on primary screening. Key figures
are the participation rates of persons who underwent screening and the number and
distribution of the examination results from cytology and HPV testing. The data on
HPV vaccinations in the context of primary screening is also considered.
Participation in primary screening: PSZ and PSK
In 2021 and 2022, just under 9.6 million (n = 9565414) entitled persons underwent
primary screening in the context of the oKFE. Of these persons, around 5.2 million
(n = 5243321) were screened in 2021 and 4.3 million (n = 4322093) were screened in
2022. This figure is based on data from insurance companies. This means that in this
period, more than one screening examination (PSZ or PSK) may be recorded for a person
insured with a statutory health insurance company (GKV).
In the group of persons aged 20–34 years entitled to have screening, the number of
women who had cytology-based screening (PSZ) increased with increasing age ([Fig. 1 ], turquoise bar). While 1.6 million women (n = 1634868) in the group aged from 20
to 24 years of age had cytology-based screening (PSZ), the figure for women aged from
25 to 29 years was just under 2 million (n = 1989109). About 2.3 million (n = 2319433)
persons in the group aged 30 to 34 years had cytology-based screening (PSZ). The highest
number of primary screening examinations using cytology and co-testing (PSK) carried
out in the group aged 35 years and above was recorded for the group aged between 35
and 39 years, with more than 800000 (n = 894625) examinations carried out. The figures
remained relatively constant for the group aged between 40 and 59 years with an average
of 440000 examinations carried out annually and then decreased with increasing age
in
the group above the age of 60 years (n = 332063). The recorded figure for persons
aged 90 and above who had screening was only just above 5000 (n = 5255) ([Fig. 1 ], red bar).
Fig. 1
Number of persons entitled to screening above the age of 20 years investigated using
primary screening (PSZ and PSK) in the years 2021 and 2022.
[Fig. 2 ] presents the number of cytology-based cervical screening (PSZ) examinations per
reporting year and age group and shows that about 3 million persons entitled to screening
in the group aged from 20 to 34 years made use of the annual cytology-based primary
screening they were entitled to each year. This corresponds to an approximate annual
participation rate of 45% of insured persons entitled to screening based on the KM
6 statistics (statistics about the number of persons insured by statutory insurance
companies in Germany) [20 ]. It is currently difficult to calculate the annual participation rate for the cohort
aged 35 years and above entitled to have PSK (screening with co-testing) because their
participation cycle covers three years. Around 2.3 million women had screening with
co-testing in 2021 and around 1.3 million women underwent screening with co-testing
in
2022 ([Fig. 3 ]). The participation rates (in percent) will only be available for this group of
persons after data has been collected and reviewed for several years.
Fig. 2
Annual number of persons entitled to screening (aged 20–34 years) who had PSZ (cytology-based
screening) in the years 2021 and 2022.
Fig. 3
Annual number of persons entitled to screening (aged 35 years and above) who had PSK
(screening with co-testing) in the years 2021 and 2022.
Results of cytology-based primary screening for persons entitled to screening aged
20–34 years
Just under 6 million (n = 5943410) persons entitled to have screening had PSZ (cytology-based
screening) in 2021 and 2022 (insurance-based data). Of these, 2.9 million (n = 2918836)
insured persons were screened in 2021 and 3.0 million (n = 3024574) insured persons
were screened in 2022 ([Fig. 3 ]).
Over the two years, around 6.0 million (n = 6062254) Pap smears were taken for cytological
examination (examination-based data). In 228149 cases, primary screening was recorded
but no information about the results of the Pap smear was documented, meaning that
there are no results available for 3.76% of examinations. Of the 6.0 million samples,
0.38% (n = 23130) were classified as group 0. This category is used to describe technically
unsatisfactory material which cannot be assessed. According to MNK III, the Pap smear
is repeated in these cases.
After the number of results for all documented cytological examinations carried out
in the context of PSZ (n = 6062254) was adjusted by subtracting the smears for which
no findings were reported (n = 228149, cytological findings “not reported”), a total
of 5.8 million (n = 5834105) findings from cytology smears were available for evaluation
for the years 2021 and 2022. Of these, 97% (n = 5650042) were found to be unremarkable;
0.4% (n = 26375) were unremarkable but the medical history was suspicious; 2.3% (n = 134558)
of findings were suspicious, and 0.4% (n = 23130) could not be assessed. Overall,
95.86% of the documented PSZ smears could be evaluated.
[Table 1 ] provides an overview of all documented results for the cytological examinations
carried out in the context of PSZ. Findings were classified as follows using the MNK
III:
Table 1
Results of the cytological examinations carried out in the context of PSZ (cytology-based
screening) in 2021 and 2022 in persons aged from 20 to 34 years, classified using
the Munich Nomenclature III.
Cytological findings
Number
In percent
0
23130
0.38154%
I
5650042
93.20035%
II-a
26375
0.43507%
II-e
721
0.01189%
II-g
6281
0.10361%
II-p
47673
0.78639%
III-e
435
0.00718%
III-g
1191
0.01965%
III-p
4294
0.07083%
III-x
86
0.00142%
IIID1
55193
0.91044%
IIID2
13338
0.22002%
IVa-g
270
0.00445%
IVa-p
4834
0.07974%
IVb-g
28
0.00046%
IVb-p
128
0.00211%
V-e
5
0.00008%
V-g
10
0.00016%
V-p
35
0.00058%
V-x
36
0.00059%
Not reported
228149
3.76344%
Total
6062254
100.00000%
The majority of findings (93.20%) were classified as group I (n = 5650042 smears),
which means they were categorized as unremarkable. 2.23% (n = 134558) of findings
were identified as suspicious and included precancerous lesions and malignancies.
A very small percentage (0.44%) were classified as II-a (n = 26375 smears). This means
that the findings were unremarkable but the medical history was suspicious.
[Fig. 4 ] shows the distribution of the different subgroup categories, given as percentages,
for the group of suspicious findings detected in the context of cytology-based primary
screening. Of the 134558 suspicious findings, 41% (n = 54675) were categorized as
having limited protective value (II-p, II-g and II-e). A further 41% (n = 55193) of
smears were categorized as dysplastic findings with a greater tendency to regression
and cell formation indicating slight dysplasia (IIID1, analogous to CIN 1). Just under
10% (n = 13338) were classified as dysplasia with a greater tendency to regression
and cell formation indicating moderate dysplasia (IIID2, analogous to CIN 2). 4.46%
(n = 6006) of the smears were classified as unclear or doubtful findings (III-e, III-g,
III-p and III-x). Precancerous stages of cervical cancer (IVa-g: adenocarcinoma in
situ; IVa-p: severe dysplasia/carcinoma in situ, analogous to CIN 3; IVb-g:
adenocarcinoma in situ, invasion cannot be excluded) or IVb-p (CIN 3, invasion cannot
be excluded) were detected in 3.91% (n = 5260) of suspicious smears. A total of 0.06%
(n = 86) of findings obtained during cytology-based primary screening were categorized
as group V (malignancies) in both observation years. They included 35 findings classified
as V-p (squamous cell carcinoma), 10 findings categorized as V-g (endocervical adenocarcinoma),
5 findings classified as V-e (endometrial adenocarcinoma) and 36 findings classified
as V-x (other malignancies).
Fig. 4
Suspicious findings detected in cytological examinations carried out in persons aged
from 20 to 34 years in the context of PSZ (cytology-based screening) in 2021 and 2022
and categorized using the Munich Nomenclature III (II-a to V-x). Results are given
as percentages.
Results of primary screening with co-testing in persons aged 35 years and above: part
1 – cytology
A total of more than 3.6 million (n = 3622004) insured women entitled to have screening
were investigated in the years 2021 and 2022 using screening with co-testing (insurance-based
data). Around 2.3 million (n = 2324485) women were examined in 2021 and just under
1.3 million (n = 1297519) were examined in 2022 ([Fig. 3 ]).
Around 3.6 million (n = 3656645) smears were taken over the two years in the context
of PSK (screening with co-testing) for cytological investigation in laboratories (examination-based
data). No information was provided in 4.77% (n = 174536) of documented PSK examinations,
meaning that no results were available for these cases. Of the 3.6 million samples,
0.45% (n = 16289) were classified as group 0 (inadequate material, recommendation
to repeat the smear). Smears in this group are categorized as technically unsatisfactory
and the smear must be repeated.
After the number of results for all documented cytological examinations carried out
in the context of PSK (n = 3656645) was adjusted by subtracting the smears for which
no findings were reported (n = 174536, cytological finding “not reported”), a total
of 3.4 million (n = 3482109) findings from cytology smears were available for evaluation
for the years 2021 and 2022. Of these, 95% (n = 3323303) were unremarkable; 1.0% (n = 35005)
were unremarkable but the medical history was suspicious; 3.0% (n = 107512) of smears
were suspicious, and 0.5% (n = 16289) could not be assessed technically. 94.78% of
all documented smears could be evaluated.
[Table 2 ] provides an overview of all documented results of the cytological examinations carried
out in the context of PSK (screening with co-testing). Findings were classified as
follows using the MNK III:
Table 2
Results of the cytological examinations carried out in persons aged 35 and above in
the context of PSK in 2021 and 2022, classified using the Munich Nomenclature III.
Cytological findings
Number
In percent
0
16289
0.44546%
I
3323303
90.88394%
II-a
35005
0.95730%
II-e
5363
0.14666%
II-g
7094
0.19400%
II-p
32683
0.89380%
III-e
2073
0.05669%
III-g
2278
0.06230%
III-p
8014
0.21916%
III-x
438
0.01198%
IIID1
30491
0.83385%
IIID2
9818
0.26850%
IVa-g
527
0.01441%
IVa-p
6453
0.17647%
IVb-g
97
0.00265%
IVb-p
561
0.01534%
V-e
379
0.01036%
V-g
202
0.00552%
V-p
888
0.02428%
V-x
153
0.00418%
Not reported
174536
4.77312%
Total
3656645
100.00000%
The majority (90.88%) of findings were categorized as group I (n = 3323303) and were
therefore considered unremarkable. 2.94% (n = 107512) of smears carried out in the
context of PSK (screening with co-testing) were identified as suspicious. A small
percentage (0.95%; n = 35005 smears) were categorized as II-a, meaning that the findings
were unremarkable but the medical history was suspicious.
[Fig. 5 ] shows the distribution of the different subgroups, given as percentages, for the
group of suspicious findings obtained in the context of primary screening with co-testing.
Of the smears with suspicious findings (from II-e and findings “not reported”, n = 107512),
42% (n = 45140) were categorized as having limited protective value (II-p, II-g and
II-e). About 28% (n = 30491) of suspicious smears were categorized as dysplastic findings
with a greater tendency to regression and cell formation indicating slight dysplasia
(IIID1, analogous to CIN 1). Just over 9% (n = 9818) of suspicious findings were categorized
as dysplasia with a greater tendency to regression and cell formation indicating moderate
dysplasia (IIID2, analogous to CIN 2). Unclear or doubtful findings (III-e, III-g,
III-p III-x) were detected in 12% (n = 12803) of suspicious cases. Precancerous stages
of cervical cancer were detected in 7% (n = 7638) of
suspicious smears (IVa-g: adenocarcinoma in situ; IVa-p: severe dysplasia/carcinoma
in situ, analogous to CIN 3; IVb-g: adenocarcinoma in situ, invasion cannot be excluded,
and IVb-p: CIN 3, invasion cannot be excluded).
Fig. 5
Suspicious findings detected in cytological examinations carried out in persons aged
35 years and above in the context of PSK (screening with co-testing) in 2021 and 2022
categorized using the Munich Nomenclature III (II-a to V-x). Results are given as
percentages.
In both observation years, a total of 1.5% (n = 1622) of cytological smears taken
during primary testing using co-testing were identified as group V (malignancies).
This included 888 findings classified as V-p (squamous cell carcinoma), 202 results
categorized as V-g (endocervical adenocarcinoma), 379 findings classified as V-e (endometrial
adenocarcinoma) and 153 findings categorized as V-x (other malignancies).
Results of primary screening with co-testing in persons aged 35 years and above: part
2 – HPV tests
Testing for human papillomavirus (HPV) is part of cervical cancer screening with co-testing
(PSK). All in all, around 3.6 million (n = 3656645) HPV tests were carried out and
documented during the two observation years of 2021 and 2022. Of these tests, 0.69%
(n = 25316) could not be evaluated, and no information was provided for 0.02% (n = 898)
of the tests ([Table 3 ]).
Table 3
Results of HPV testing carried out in the context of PSK in women aged 35 years and
above (2021 and 2022)
HPV test result
Number
Positive
312878 (8.56%)
Negative
3317553 (90.73%)
Cannot be evaluated
25316 (0.69%)
Not reported
898 (0.02%)
Total
3656645 (100.00%)
A negative test result was reported for 90.73% (n = 3317553) of HPV tests carried
out in the context of PSK and a positive test result was detected in 8.56% (n = 312878)
of HPV tests ([Table 3 ]). This means that out of 3.6 million documented HPV tests carried out in 2021 and
2022 in the context of PSK, infection with HPV was detected in fewer than 9%.
[Table 4 ] presents the results of the cytological examinations carried out in the context
of PSK. These results are juxtaposed with the relevant results from the related HPV
tests. Of all the HPV tests carried out in the context of PSK, no information about
the results of cytological screening was available for 174536 (4.77%) of tests. Of
these tests, 89.78% (n = 156697) of tests were negative and 7.34% (n = 12815) were
positive.
Table 4
Overview of the results of HPV testing for different groups of cytological findings
identified during cervical cancer screening with co-testing (PSK) in 2021 and 2022
in women aged 35 years and above.
Cytological finding
Test result
Positive
Negative
Cannot be evaluated
Not reported
Total
0
1293
13900
994
102
16289 (0.45%)
I
211705
3092942
18143
513
3323303 (90.88%)
II-a
20665
13679
658
3
35005 (0.96%)
II-e
404
4910
49
0
5363 (0.15%)
II-g
2446
4582
66
0
7094 (0.19%)
II-p
18045
14378
258
2
32683 (0.89%)
III-e
315
1725
22
11
2073 (0.06%)
III-g
1262
1005
11
0
2278 (0.06%)
III-p
6193
1775
46
0
8014 (0.22%)
III-x
111
319
8
0
438 (0.01%)
IIID1
20958
9358
174
1
30491 (0.83%)
IIID2
8577
1186
54
1
9818 (0.27%)
IVa-g
460
62
5
0
527 (0.01%)
IVa-p
6136
290
26
1
6453 (0.18%)
IVb-g
79
18
0
0
97 (0.00%)
IVb-p
507
50
4
0
561 (0.02%)
V-e
49
319
11
0
379 (0.01%)
V-g
97
98
7
0
202 (0.01%)
V-p
717
155
15
1
888 (0.02%)
V-x
44
105
4
0
153 (0.00%)
Not reported
12815
156697
4761
263
174536 (4.77%)
Total
312878 (8.56%)
3317553 (90.73%)
25316 (0.69%)
898 (0.02%)
3656645 (100.00%)
The results of around 3.3 million evaluable HPV tests (n = 3338991) are available
for the groups with unremarkable and unsuspicious findings (I and II-a), excluding
non-evaluable findings and cases where there is no information about the cytological
findings or the HPV test result. 93.04% (3106621 of 3338991) of HPV tests were negative
and 6.96% (232370 of 3338991) were positive when groups I and II-a were taken together.
However, when group II-a was considered separately, it was very noticeable that more
than half of the HPV tests of this group were positive ([Fig. 6 ]). The HP virus was confirmed in 60.17% of cases (20665 of 34344), and the test result
was negative in 39.83% (13679 of 34344) of cases.
Fig. 6
Graphical comparison of cytological findings and HPV test results for groups I and
II-a in % (cervical screening with co-testing [PSK] carried out in 2021 and 2022 in
women aged 35 years and above).
The results of 106735 evaluable HPV tests (excluding findings which cannot be evaluated
and cases where there is no information about the cytological findings or the HPV
test) were available for all groups with suspicious cytological findings (IIe–IIp,
III, IIID, IV, V). 62.21% (66400 of 106735) of these tests were positive and 37.79%
(40335 of 106735) were negative. This means that the HPV-positive rate was about 10
times higher in cases with suspicious cytological findings compared to cases where
the cytological findings were unremarkable (combined result for groups I and II-a).
In the groups with cytology findings with limited protective value or unclear or doubtful
findings (II and III) we noted that percentages of positive test results were recorded
for the respective p-subgroups ([Table 4 ],[Fig. 7 ]). Positive results were recorded less often for the subgroups e, g and x. This did
not apply to group III-g. About half of the tests in this group were negative (1005
of 2267 tests) and half were positive (1262 of 2267 tests), excluding findings which
could not be evaluated and cases where information about the cytological results or
the HPV test results was missing.
Fig. 7
Graphical comparison of cytological findings and HPV test results for groups 0 to
V in % (cervical screening with co-testing [PSK] carried out in 2021 and 2022 in women
aged 35 years and above).
The results of 40079 evaluable HPV tests carried out in the context of PSK were available
for the IIID group with dysplasia and a greater tendency to regression (this figure
excludes non-evaluable findings and cases where information about the cytological
findings or the HPV test result are missing). 30316 results of HPV tests were available
for group IIID1 and 9763 were available for group IIID2. The HPV-positive rate for
IIID1 was 69% (20958 of 30316). In the IIID2 group, the percentage of positive test
results was significantly higher with 88% (8577 of 9763) ([Fig. 7 ]).
The results of 7602 evaluable HPV tests were available for the group with cytological
results showing precancerous cervical lesions (IV according to the MNK III). This
figure excludes non-evaluable findings and cases where information about the cytological
findings or the HPV test results are missing. An HPV infection was detected in 94.48%
(7182 of 7602) of tests from all four subgroups. 5.52% (420 of 7602) of tests were
negative ([Table 4 ]). Again, a particularly high percentage of positive HPV test results was identified
in the p subgroups (IVa-p and IVb-p) ([Fig. 7 ]).
The results of 1584 evaluable HPV tests were available for the group with cytological
findings classified as malignancies (V) according to the Munich Nomenclature III.
When all four subgroups (V-e, V-g, V-p, V-x) were taken together, HPV infection was
identified in 57.26% (907 von 1584) of tests, while 42.74% (677 of 1584) of tests
were negative for HPV. When the cytological findings of the subgroups were considered
separately, the percentage of positive HPV tests was only higher in the V-p subgroup
([Fig. 7 ]), with HPV confirmed in 82.22% of tests (717 of 872). The subgroups V-g, V-e and
V-x had more negative test results (< 50%) ([Table 4 ]).
When all positive HPV samples were examined for the high-risk HPV types 16/18, HPV
types 16/18 were confirmed in around one third of samples (32.38%; 101320 of 312878)
([Table 5 ]). HPV types 16/18 were not detected in around 60% (n = 138043) of cases in the groups
with unremarkable cytological findings (I and II-a). Both high-risk variants were
identified in just under 30% (69170 of 232370) of investigated samples from these
groups. The percentage of HPV types 16/18 increased when cytological abnormalities
classified as group III or above increased ([Table 5 ]). The only exception was subgroup IIID1 in which only around 38% (7161 of 118792)
of smears were positive for the high-risk HPV types 16/18 with the two high-risk viruses
not found in more than 60% (11631 of 18792) samples. HPV types 16/18 were present
in just over half of the samples categorized as IIID2 (50%, 3940 of 7786) and
were not detected in just under half (49%, 3846 of 7786).
Table 5
HPV types 16/18 detected in positive HPV tests carried out in the context of cervical
screening with co-testing (PSK) in women aged 35 years and above (2021/2022).
Cytological findings
HPV type 16/18 yes
HPV type 16/18 no
Virus type cannot be differentiated
Total
0
390
786
117
1293
I
63690
125263
22752
211705
II-a
5480
12780
2405
20665
II-e
113
246
45
404
II-g
998
1237
211
2446
II-p
6211
9833
2001
18045
III-e
144
140
31
315
III-g
677
488
97
1262
III-p
3006
2688
499
6193
III-x
60
42
9
111
IIID1
7161
11631
2166
20958
IIID2
3940
3846
791
8577
IVa-g
303
128
29
460
IVa-p
3757
1945
434
6136
IVb-g
57
17
5
79
IVb-p
340
127
40
507
V-e
30
18
1
49
V-g
63
29
5
97
V-p
495
182
40
717
V-x
24
17
3
44
Not reported
4381
6869
1565
12815
Total
101320 (32.38%)
178312 (56.99%)
33246 (10.63%)
312878 (100.00%)
HPV vaccination status in the group of women entitled to have screening aged 20–34
years
Considering when the vaccines were first approved and the availability of vaccinations,
the HPV vaccination status in the group of women aged between 20 and 34 years is particularly
interesting. The birth cohort of 1990 is the first age group in which a significant
number of insured women could already be vaccinated. The vaccination status was determined
in the context of the oKFE and was confirmed by a certificate of vaccination or was
based on information voluntarily disclosed by the insured women. There are no detailed
scientifically collected data on HPV vaccination status in Germany.
When all of the 6062254 recorded primary screenings of the group aged from 20 to 34
years (PSZ) were reviewed, no information about their vaccination status was available
for < 0.01% (52 of 6062254). The vaccination status was not clear for 13.81% (837203
of 6062254) of screenings. No information about the cytological results was available
for 3.76% (228147 of 6062254) of the documented examinations. These cases are not
included in the further evaluation below, as they cannot be categorized in accordance
with MNK III. This leaves 5834105 examination results for which possible connections
between cytological findings and vaccination status can be reviewed. More than half
(54.19%) of the women for whom cytological findings were available (3161575 of 5834105)
had not been vaccinated against HPV. About 30.40% (1773296 of 5834105) of women screened
in the context of PSZ aged between 20 and 34 years had been fully vaccinated against
HPV. Incomplete vaccination status was
recorded for 1.69% (98327 of 5834105) of women screened in the context of PSZ ([Table 6 ]).
Table 6
Documented HPV vaccination status for different cytological groups categorized using
the MNK III. Data were collected in 2021/2022 in the context of PSZ (cervical cancer
screening carried out in women aged 20–34 years).
Cytological findings – vacc. status
Complete
Incomplete
None
Unclear
Not reported
Total
0
5587 (0.30%)
296 (0.29%)
12712 (0.39%)
4520 (0.54%)
15 (28.85%)
23130 (0.38%)
I
1723611 (94.01%)
94690 (92.75%)
3058417 (92.97%)
773301 (92.37%)
23 (44.23%)
5650042 (93.20%)
II-a
7531 (0.41%)
810 (0.79%)
14444 (0.44%)
3590 (0.43%)
0 (0.00%)
26375 (0.44%)
II-e
183 (0.01%)
16 (0.02%)
408 (0.01%)
114 (0.01%)
0 (0.00%)
721 (0.01%)
II-g
1542 (0.08%)
104 (0.10%)
3814 (0.12%)
821 (0.10%)
0 (0.00%)
6281 (0.10%)
II-p
14108 (0.77%)
924 (0.91%)
25837 (0.79%)
6804 (0.81%)
0 (0.00%)
47673 (0.79%)
III-e
119 (0.01%)
9 (0.01%)
245 (0.01%)
60 (0.01%)
2 (3.85%)
435 (0.01%)
III-g
225 (0.01%)
11 (0.01%)
783 (0.02%)
172 (0.02%)
0 (0.00%)
1191 (0.02%)
III-p
759 (0.04%)
75 (0.07%)
2814 (0.09%)
646 (0.08%)
0 (0.00%)
4294 (0.07%)
III-x
19 (0.00%)
1 (0.00%)
56 (0.00%)
10 (0.00%)
0 (0.00%)
86 (0.00%)
IIID1
16058 (0.88%)
1071 (1.05%)
30025 (0.91%)
8039 (0.96%)
0 (0.00%)
55193 (0.91%)
IIID2
2924 (0.16%)
255 (0.25%)
8212 (0.25%)
1947 (0.23%)
0 (0.00%)
13338 (0.22%)
IVa-g
25 (0.00%)
5 (0.00%)
201 (0.01%)
39 (0.00%)
0 (0.00%)
270 (0.00%)
IVa-p
579 (0.03%)
57 (0.06%)
3436 (0.10%)
762 (0.09%)
0 (0.00%)
4834 (0.08%)
IVb-g
2 (0.00%)
0 (0.00%)
24 (0.00%)
2 (0.00%)
0 (0.00%)
28 (0.00%)
IVb-p
9 (0.00%)
1 (0.00%)
93 (0.00%)
25 (0.00%)
0 (0.00%)
128 (0.00%)
V-e
1 (0.00%)
1 (0.00%)
2 (0.00%)
1 (0.00%)
0 (0.00%)
5 (0.00%)
V-g
3 (0.00%)
0 (0.00%)
4 (0.00%)
3 (0.00%)
0 (0.00%)
10 (0.00%)
V-p
2 (0.00%)
0 (0.00%)
26 (0.00%)
7 (0.00%)
0 (0.00%)
35 (0.00%)
V-x
9 (0.00%)
1 (0.00%)
22 (0.00%)
4 (0.00%)
0 (0.00%)
36 (0.00%)
Not reported
60095 (3.28%)
3768 (3.69%)
127938 (3.89%)
36336 (4.34%)
12 (23.08%)
228149 (3.76%)
Total
1833391 (100.00%)
102095 (100.00%)
3289513 (100.00%)
837203 (100.00%)
52 (100.00%)
6062254 (100.00%)
When the group of women entitled to have PSZ screening were divided into three age
groups, an increasing trend to vaccination was found in the younger age groups. In
the youngest group, aged 20 to 24 years, 44% had already been fully vaccinated. In
the group of women aged 30 to 34 years only 17% of examined women were fully vaccinated
([Fig. 8 ]). It became clear that if women were vaccinated, they were almost always fully vaccinated.
Only a very small percentage of investigated women (< 2% in all three age groups)
had only had a single vaccination and were therefore not fully vaccinated and lacked
full vaccination protection.
Fig. 8
HPV vaccination status of women who underwent PSZ screening in 2021 and 2022 (aged
between 20 and 34 years), grouped according to age. Data are given in percent.
Discussion
It is important to ensure that the gratifying decline in the number of new cases with
cervical cancer is not merely maintained but reduced even further [21 ]. This was why the structured cancer screening program for the early detection of
cervical cancer was set up in 2020. The aim of establishing qualitative monitoring
using data-driven assessments of the available measures is to ensure that the program
will be developed further at a professional and organizational level.
The decisive part is participation in screening. As outlined in the oKFE-RL, persons
entitled to be screened are invited to attend a screening appointment and provided
with information about the screening. The aim is to motivate persons entitled to have
screening to make full use of the available screening and significantly increase screening
rates. The participation rates for cytology-based primary screening in the group of
women aged from 20 to 34 years was about 45% for both of the investigated data years
(2021 und 2022), based on the KM 6 statistics. Because of the new data pool and changes
in screening entitlement, a direct comparison with data collected in the years prior
to 2020 is possible only to a limited extent. A study using healthcare data from the
German federal state of Lower Saxony revealed an annual participation rate for cervical
cancer screening of about 50% for the period from 2006 to 2011 [22 ].
However, this rate can only serve as a rough orientation because participation rates
vary across the different German federal states in this period and not all federal
states had set up organized screening programs in the period under review. If we look
at an organized cancer screening program in Germany where participants are invited
to attend and which has existed for a long time such as the mammography screening
program, the participation rates are similar. In 2021, 3031022 women out of 5887028
invited women participated in the mammography screening program. When women who self-request
screening are included in the assessment, then 51.5% of all invited women participated
[23 ]. In the period from 2005 to 2021, when the mammography screening program was implemented
in its current form, the participation rate levelled off at around 50% after some
initial fluctuations. The somewhat lower participation rates reported for the
first two years of the newly established organized screening program for cervical
cancer does not necessarily indicate that participation rates are actually decreasing.
This was borne out when the billing figures provided by the National Association of
Statutory Health Insurance Physicians in Germany (Kassenärztliche Bundesvereinigung , KBV) for cytology-based primary screening for the year 2019 (Physicians Fee Schedule
[EBM ] code 01730: 4076811) were compared with those of 2021 (EBM codes 01760 and 01761: 3748074). Instead, it must be assumed that participation was
underestimated, as the data for 2020 which was the year of the changeover could not
be included in the analysis. Whether the reorganization and the switch to issuing
invitations for screening will result in a gradual increase in participation rates
will only be clear in the coming years when longer measurement periods will be available
for analysis. At the moment, the figures indicate that the
focus with regards to women entitled to have cervical screening in the context of
PSZ should be on motivating younger women to take part.
An assessment of the participation rates for primary screening with co-testing of
women aged 35 and above is currently not possible, as they are only entitled to have
screening every three years and the data for 2020 could not be included in this analysis.
The second cycle of invitations issued to attend cervical cancer screening appointments
will cover the period from 2023 to 2025. When this data is evaluated, it will be possible
to start interpreting the data on the participation rates of women aged 35 years and
above and to consider whether measures to increase participation rates would be feasible,
and if so, which ones.
The findings of just under 96% of the around 6 million Pap smears obtained in the
context of PSZ screening could be evaluated. No information on the findings was available
for just over 3% of examinations. 0.4% of samples were categorized as 0, which means
that they were considered technically unsatisfactory, non-evaluable samples. This
low percentage is similar to the figures reported for the years 2017 to 2019 [24 ]. About 97% of evaluable smears obtained in the context of PSZ, excluding findings
for which no information was provided, were categorized as unremarkable or not suspicious
(group I according to MNK III). These results correspond to reference data from 2019
where about 97% of cytological findings were classified as group I according to MNK III
[24 ]. All other cytology subgroups identified in the context of cervical cancer screening
were under 1%,
respectively. The percentage of findings obtained in 2021 and 2022 in the context
of cytology-based screening which were categorized as group IV or V (MNK III) was
less than 0.01% for each subgroup, with the exception of subgroup IVa-p (0.08%) ([Fig. 9 ]). Again, these results are similar to the reference data for 2019 presented by Schenck
et al. in 2023, in which all subgroups (with the exception of subgroup IVa-p which
was 0.15%) were recorded as < 0.01% in the annual statistics. The focus in the coming
years will be on findings classified as group IV and V. When the data from the newly
introduced general screening program is compared with the reference data, it is important
to be aware of the scope of the data used in the annual statistics for 2019 [24 ]. In addition to the cytological results obtained from primary screening and from
examinations carried out to investigate
suspicious findings, the statistics for 2019 also include findings obtained in the
context of birth control as well as the results of curative cytological examinations.
Fig. 9
Comparison of the distribution of unclear and suspicious smears categorized according
to MNK III for findings obtained with cytology-based screening (PSZ) and findings
obtained from primary screening with co-testing (PSK) collected in 2021 and 2022.
Data are presented in percent.
The evaluation report includes just under 3.6 million cytological examinations carried
out in 2021 and 2022 in women aged 35 and above in the context of primary screening
with co-testing (PSK). Similar to the data obtained from screening carried out in
the context of cytology-based screening (PSZ), about 95% of smears could be evaluated.
No information on findings was available for about 5% of examinations. 0.4% of samples
were categorized as 0, which means they were technically unsatisfactory, non-evaluable
samples. Again, the majority (95%) of the examinations carried out in the context
of PSK were unremarkable or not suspicious (group I according to MNK III) after the
findings for which no information was available had been subtracted. A comparison
with the reference data from 2019 [24 ] showed similar trends. All other subgroups identified during screening examinations
carried out in the context of PSK were less than
1%, and only a few cytological findings of precancerous lesions and cervical malignancies
were detected. The highest percentage of any subgroup in groups IV and V were findings
categorized as IVa-p (0.176%). A comparison with the reference data (IVa-p: 0.146%)
shows that the figures for 2019 were similar [24 ]. Findings classified as group IV or V were found more often in the group of women
aged 35 and above investigated in the context of PSK compared to women aged 20 to
34 years investigated in the context of PSZ. The higher percentage of findings categorized
as IV-p in the group of women aged 35 years and above is particularly noticeable ([Fig. 9 ]). This development will need to be monitored in future.
The percentage of positive HPV tests increased as the severity of cytological findings
increased from group II to group IV (MNK III). The highest positive rate in all groups
was recorded for p-type findings. This trend increased significantly from group II
to group V. However, findings categorized as V-g and V-p where the HPV test results
were negative need to be examined more closely. Around 50% of HPV tests for the subgroup
classified as V-g and about 20% of HPV tests for the subgroup categorized as V-p were
negative. These suspicious findings were discovered through combined screening. This
will need to be monitored and critically reviewed when the data is analyzed in the
years to come.
Out of 6.0 million examinations carried out in the context of PSZ (cytology-based
screening) 86 findings were identified and categorized as V-g (endocervical carcinoma).
Out of 3.7 million examinations carried out in the context of PSK (screening with
co-testing), 1622 findings were identified and categorized as V-g (endocervical carcinoma).
The clear difference between these figures showing cytological evidence of carcinoma
in the two cohorts can be largely explained by the age difference between the two
groups. In general, cervical cancer occurs less often in younger women below the age
of 35 years. The incidence of cervical cancer increases with increasing age and peaks
between the ages of 35 and 55 years [25 ]
[26 ].
In almost all cases, cervical cancer is caused by HPV [27 ]. According to the RKI guideline on the human papillomavirus, the currently available
HPV vaccines provide almost 100% protection against infection with the HPV types contained
in the vaccines [28 ]. This means that recording the vaccination status when documenting cytology results
is relevant. It is important to be aware that this data is based on information obtained
from vaccination cards or from self-disclosure by the insured woman herself and is
therefore neither comprehensive nor was it collected scientifically. The fact that
more than 30% of insured persons between 20 and 34 years are fully vaccinated against
HPV is positive. In view of the data on the severity of cytological findings and the
number of positive HPV tests, the importance of HPV vaccinations must be stressed,
and further evaluation of this
data in the coming years will be useful. Conclusions with regards to possible correlations
are currently not meaningful because of the small number of cases and the limitations
of the data.
The first assessment of the effectiveness of the newly developed screening program
for the early detection of cervical cancer faces a number of challenges. The transition
year 2020 was not included in the data collection, some of the data on the results
of examinations was incomplete, and not all cancer registries of the German federal
states had been linked to the program at the time of the first data evaluation for
the years 2021 and 2022. Because of these limitations, it is currently not possible
to make reliable statements about key issues. The coronavirus pandemic in 2020–2022
also had an impact. In Germany, the effects were appreciable, but the extent of the
impact varied. Adults were more affected by cancellations and postponements of appointments.
In contrast, screening examinations and vaccination rates of children remained largely
stable with only slight delays [29 ]
[30 ]. Questions about the acceptance of the screening program by the target group and
the effect of issuing invitations to attend screening on participation rates can therefore
only be answered after a longer observation period. An informed assessment of the
organized screening program will only be possible when the data basis has been completed
and data from the cancer registries of the federal states has also been included in
the evaluation. Until then, this first evaluation of the new program must be viewed
with caution.
