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373 Human Papilloma Viruses Genome June July 2011 Letter 20110831a.doc 1
I N S T A N D e. V. Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laboratorien e. V. (vormals Hämometerprüfstelle)
WHO Collaborating Centre for Quality Assurance
and Standardization in Laboratory Medicine
in cooperation with
Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) Gesellschaft für Virologie (GfV) Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM)
EQAS Adviser: Assistant EQAS Adviser:
Prof. Dr. Heinz Zeichhardt Dr. Hans-Peter Grunert CharitéCentrum für diagnostische und präventive Labormedizin Institut für Biotechnologische Diagnostik in der GBD Institut für Virologie, Campus Benjamin Franklin Potsdamer Chaussee 80, 14129 Berlin Hindenburgdamm 27, 12203 Berlin Tel.: +49-(0)30-688197730; Fax: +49-(0)30-688197741 Tel.: +49-(0)30-84453625/23; Fax: +49-(0)30-84453626 Email: [email protected] Email: [email protected]
August 2011
Final Report External Quality Assessment Scheme (EQAS) - June/July 2011
Virus Genome Detection - Human Papilloma Viruses (373) Differentiation of “High Risk” and “Low Risk” Types and Typing
(PCR/NAT HPV) INSTAND-Target Value Laboratories:
Uniklinik Köln, Institut für Virologie, Nationales Referenzzentrum für Papillom- und Polyomaviren: Prof. Dr. H. Pfister, Prof. Dr. U. Wieland, Dr. R. Kaiser
Charité - Universitätsmedizin Berlin, Campus Mitte, Institut für Medizinische Virologie, Nationales Konsiliarlaboratorium für Hantaviren: Prof. Dr. D. H. Krüger, PD Dr. J. Hofmann
Klinikum der Johann Wolfgang Goethe-Universität, Institut für Medizinische Virologie, Frankfurt/Main: Prof. Dr. H. W. Doerr, Prof. Dr. H. Rabenau, PD Dr. A. Berger, Dr. R. Allwinn
Labor Enders, Institut für Virologie, Infektiologie und Epidemiologie, Stuttgart: Prof. Dr. Gisela Enders & Partner
Universitätsklinikum des Saarlandes, Institut für Virologie, Homburg/Saar; Prof. Dr. S. Smola, Prof. Dr. N. Müller-Lantzsch
INSTAND-Geschäftsstelle
Ubierstr. 20 40223 Düsseldorf Telefon: +49 (0)211 1592 13 0 Fax: +49 (0)211 1592 1330 E-mail: [email protected] Internet: www.instand-ev.de
373 Human Papilloma Viruses Genome June July 2011 Letter 20110831a.doc 2
Dear colleagues,
Attached please find the final report for the EQAS "PCR-/NAT-HPV". Your certificate of successful participation, statement of participation and statement of your individual results (validity period: 12 months) were sent out independently. The following test categories are individually stated on the documents:
20. Differentiation between "High Risk"- and "Low Risk" HPV - Differenzierung von HPV in "High Risk"- und "Low Risk"-Typen
25. Typing of "High Risk" HPV and detection of "Low Risk" HPV (without typing) - Typisierung von "High Risk"-HPV und Nachweis von "Low Risk"-HPV (ohne Typisierung)
30. Typing of HPV - Typisierung von HPV
35. Typing of "High Risk" HPV (without determination of "Low Risk" HPV) - Typisierung von "High Risk"-HPV (ohne Bestimmung von "Low Risk"-HPV)
60. Determination of "High Risk" HPV (without determination of "Low Risk" HPV) - Bestimmung von "High Risk"-HPV (ohne Bestimmung von "Low Risk"-HPV)
The report for this EQA scheme is also available as PDF file on the INSTAND-Homepage under EQAS / Reports / Year and Category (Virus genome detection) in English language (http://www.instandev.de/en/eqas/reports/ ) and German language (http://www.instandev.de/ringversuche/kommentare/ ).
Sample properties and evaluation
In this EQAS the test results are requested as follows for:
Differentiation: “High Risk”, “Low Risk”, "below level of detection/negative“ or "indeterminate“; Typing: HPV type (e.g. “HPV 6” = “6” = “human papilloma virus type 6”)
Sample properties were as follows:
Sample 373011: HPV 18 positive; lysate of HeLa cells, containing sequences of HPV 18. Sample 373012: HPV 16 low positive; lysate of SiHa cells, containing sequences of HPV 16. Please see comment to sample 373012. Sample 373013: Biopsy material of a condyloma. The biopsy material is HPV 6 positive as analyzed by the INSTAND-Target Value Laboratories.
Sample 373014: HPV 18 positive; lysate of HeLa cells, containing sequences of HPV 18. Sample 373015: HPV negative; lysate of MRC-5 cells (human lung fibroblasts), no HPV genome detectable.
The HPV 18 positive samples 373011 and 373014 represented different dilution steps of a dilution series of a lysate of HeLa cells.
Please see table 1 for details on sample properties, results and success rates.
A result was not considered for evaluation in case you had specified that this result should only be taken as additional information and ignored as valid result.
For receiving a certificate of successful participation it is required that you analyzed all 5 samples of the sample set correctly with the same method in the corresponding test categories (100% correct results).
The evaluation criteria for the results of EQA schemes in virology follow the new Guideline of the German Medical Association (Bundesärztekammer/ RiliBÄK = Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen). Please see section B2 of the RiliBÄK "qualitative determinations in laboratory medicine = Qualitative laboratoriumsmedizinische Untersuchungen" (effective since 01.07.2011 with a transition period of two years; Deutsches Ärzteblatt, Jg. 108, Heft 30, 29.07.2011, Seite A 1647-1651). Section B3 of the RiliBÄK "direct detection and characterization of infectious diseases pathogens = Direkter Nachweis und Charakterisierung von Infektionserregern" is in progress.
Results
The results are summarized and differentiated for each sample according to test category 20, 25, 30, 35 and 60, respectively, in table 1. Detailed results for the detection and differentiation between "High Risk" and "Low Risk" HPVs as well as for typing are shown in the following tables.
Comment to sample 373012: Sample 373012 is low positive for HPV 16 due to the adjusted concentration of SiHa cells, which contain sequences of HPV 16. The INSTAND-Target Value Laboratories pre-tested this sample. Laboratories which applied PCR test systems reported HPV positive results for this sample whereas a laboratory which used a
373 Human Papilloma Viruses Genome June July 2011 Letter 20110831a.doc 3
hybridization test (e.g. HPV screening test principle Hybrid Capture 2 Technology/Qiagen) reported negative results.
It could already be shown in previous EQA schemes that screening by hybridization methods for the detection of "High Risk" HPV types revealed a lower analytical sensitivity in comparison to PCR detection methods.
In this EQA scheme those results for sample 373012 which were received by application of the HPV-screening test "Hybrid Capture 2 Technology/Qiagen" were not evaluated for test categories 20 and 60 (without disadvantage for the certificate). The manufacturer concerned has already been informed.
In recent years samples containing "High Risk" or "Low Risk" HPV types in different concentrations have sporadically been included into the EQA schemes in order to get insight into the analytical sensitivities of the different applied test systems. Objective of the INSTAND EQA schemes is to assess the performance of screening methods in comparison to the more sensitive PCR test systems including consecutive typing.
The question of different analytical sensitivities of diverse methods for the detection of HPV was already addressed by the Jointed Diagnostic Council of the Deutsche Vereinigung zur Bekämpfung von Viruskrankheiten (DVV) and the Gesellschaft für Virologie (GfV) in accordance with Prof. Dr. H. Pfister, Director of the Nationales Referenzzentrum für Papillom- und Polyomaviren, Uniklinik Köln, Institut für Virologie, in August 2007. Test systems which show differences in analytical sensitivity are desirable and should be applied depending on the clinical status of the patient.
The lower sensitivity of hybrid capture tests can be adequate or even of advantage for screening of cervical carcinoma and early detection of cervical intraepithelial neoplasia (CIN) under the prerequisite that these tests are able to detect not only HPV 16 and HPV 18 but also other relevant "High Risk" HPV types.
Enhanced sensitivity of PCR/NAT for the detection of HPV genome is desirable for:
the detection of adenocarcinoma and for the early detection of adenocarcinoma in situ,
the triage of women with cytologic diagnosis ASCUS (atypical squamous cells of undetermined significance),
the control of women after therapy.
Typing of HPV by PCR/NAT is reasonable for:
the differentiation between reactivation of persisting HPV infection and primary infection/reinfection with a new HPV type,
the detection of multiple HPV types in immunocompromised patients. Comments to test categories
Test category 35: Typing of "High Risk" HPV (without determination of "Low Risk" HPV) These tests exclusively detect and type "High Risk" HPV and cannot detect "Low Risk" HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk" HPV. Results representing "negative for High Risk HPV" will be stated as "negative" in your statement of individual results.
Test category 60: Determination of "High Risk" HPV (without determination of "Low Risk" HPV) These tests exclusively detect "High Risk" HPV (without specification of the HPV type) and cannot detect "Low Risk" HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk HPV". Results representing "negative for High Risk HPV" will be stated as "negative" in your statement of individual results.
Determination of "High Risk“ HPV E6/E7 mRNA One laboratory applied a TMA test for the detection of "High Risk“ HPV E6/E7 mRNA. This test was assigned to test category 60 because this test system only detects E6/E7 mRNA of a distinct number of "High Risk" HPV types.
We gratefully acknowledge the good cooperation with Prof. Dr. H. Pfister, Prof. Dr. U. Wieland and Dr. R. Kaiser (Nationales Referenzzentrum für Papillom- und Polyomaviren, Institut für Virologie, Universität Köln) as well as Prof. Dr. H.-P. Berlien and Dr. U. Müller (Evangelische Elisabeth Klinik, Berlin). We additionally thank Dr. M. Enders and Dr. G. Schalasta (Labor Prof. Gisela Enders und Partner, Stuttgart) for the studies on suitability of the EQA samples for the detection of "High Risk" HPV E6/E7 mRNA by a TMA test system.
Thank you very much for your kind cooperation.
Prof. Dr. H. Zeichhardt
373 Human Papilloma Viruses Genome June July 2011 Letter 20110831a.doc 4
Table 1: Summary of sample properties, results and success rates
Sample 373011* Sample 373012# Sample 373013 Sample 373014* Sample 373015
Success rates for all
5 samples of the sample set&
Properties HPV
positive HPV
positive#
HPV positive
HPV positive
HPV negative
High Risk or Low Risk
High Risk High Risk# Low Risk High Risk negative
Type type 18 type 16# type 6 type 18 negative
Material lysate of HeLa cells lysate of SiHa cells# biopsy material lysate of HeLa cells lysate of MRC-5 cells
Dilution 1 : 50* 1 : 1.6 1 : 25 1 : 100* ---
considered as correct results for test category 20: differentiation between "High Risk" and "Low Risk" HPV (human papilloma viruses)
High Risk High Risk# Low Risk High Risk negative
91.1%&#
(82/90)
98.9% (91/92)
91.9%#
(57/62)#
97.8% (90/92)
94.6% (87/92)
98.9% (91/92)
considered as correct results for test category 25: typing of "High Risk" HPV and detection of "Low Risk" HPV (without typing)
HPV 18 HPV 16 Low Risk HPV 18 negative / not done 100%
&
(7/7) 100% (7/7)
100% (7/7)
100% (7/7)
100% (7/7)
100% (7/7)
considered as correct results for test category 30: typing of HPV
HPV 18 HPV 16 HPV 6 HPV 18 negative / not done 88.2%
&
(67/76) 98.7% (76/77)
92.2% (71/77)
100% (78/78)
97.4% (75/77)
98.7% (76/77)
considered as correct results for test category 35: typing of "High Risk" HPV (without determination of "Low Risk" HPV)
HPV 18 HPV 16 negative for High Risk-HPV HPV 18 negative for High Risk-HPV 100%
&
(7/8) 100% (8/8)
100% (8/8)
100% (7/7)
100% (8/8)
100% (8/8)
considered as correct results for test category 60: determination of "High Risk" HPV (without determination of "Low Risk" HPV)
High Risk High Risk# negative for High Risk-HPV High Risk negative for High Risk-HPV
88.9&#
(16/18)
94.4% (17/18)
100%#
(11/11)#
94.4% (17/18)
100% (18/18)
94.4% (17/18)
* Samples represent different dilution steps of the same dilution series of a lysate of HeLa cells. #
Sample 373012 is low positive for HPV 16 due to the adjusted concentration of SiHa cells, which contain sequences of HPV 16. The results for the HPV screening test principle "Hybrid Capture 2 Technology/Qiagen" reported for test categories 20 and 60, respectively, were not evaluated (without disadvantage for the certificate). For details see comment to sample 373012.
& The success rates for all 5 samples of the corresponding sample set of test categories 20, 25, 30, 35 and 60, respectively, refer to the number of participating laboratories. Laboratories having reported results obtained by several methods are recorded only once in the corresponding test category.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 1
INSTAND e. V., Gesellschaft zur Förderung der Qualitätssicherung in medizinischen
Laboratorien e. V. (vormals Hämometerprüfstelle) - www.instand-ev.de
in cooperation with
Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten e. V. (DVV)
Gesellschaft für Virologie e. V. (GfV)
Deutsche Gesellschaft für Hygiene und Mikrobiologie e. V. (DGHM)
EQAS Virology June/July 2011
Virus genome detection PCR- / NAT-HPV (Human Papilloma Viruses) (373)
Results for sample 373011
20. Differentiation between "High Risk" and "Low Risk" HPV
Correct result: High Risk
test results in total total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
92 91 1 0 0 98.9%
method / manufacturer total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
hybridization (70) 76 75 1 0 0 98.7%
PCR / hybridization (1170)
Chipron / Chipron 3 3 100.0%
Gen ID (AID) / Gen ID (AID) 12 12 100.0%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 4 4 100.0%
Innogenetics / Innogenetics 10 10 100.0%
Roche / Roche 6 6 100.0%
in house / Qiagen 1 1 100.0%
in house / Roche 1 1 100.0%
in house / other manuf. 1 1 100.0%
other manuf. / other manuf. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 4 4 100.0%
hybridization / hybridization (3070)
Qiagen / Qiagen 30 30 100.0%
other PCR / hybridization (9870)
astra Diag. / astra Diag. 1 1 0.0%
sequencing (72) 11 11 0 0 0 100.0%
PCR / sequencing (1172)
in house / in house 6 6 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manuf. / other manuf. 1 1 100.0%
other test (99) 5 5 0 0 0 100.0%
PCR / other test (1199)
in house / in house 4 4 100.0%
nested PCR / other test (1299)
in house / in house 1 1 100.0%
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 2
Results for sample 373011
25. Typing of "High Risk" HPV and detection of "Low Risk" HPV (without typing)
Correct result: HPV 18
test results in total total type
HPV 18 other type
below level of detection/ negative
correct
results
%
7 7 0 0 100.0%
method / manufacturer total type
HPV 18 other type
below level of detection/ negative
correct
results
%
hybridization (70) 5 5 0 0 100.0%
PCR / hybridization (1170)
Gen ID (AID) / Gen ID (AID) 5 5 100.0%
other test (99) 2 2 0 0 100.0%
PCR / other test (1199)
in house / in house 1 1 100.0%
LightCycler / other test (4099)
in house / in house 1 1 100.0%
Results for sample 373011
30. Typing of HPV
Correct result: HPV 18
test results in total total type
HPV 18 other type
below level of detection/ negative/ not stated
correct
results
%
77 76 1 0 98.7%
method / manufacturer total type
HPV 18 other type
below level of detection/ negative/ not stated
correct
results
%
hybridization (70) 58 57 1 0 98.3%
PCR / hybridization (1170)
Chipron / Chipron 7 7 100.0%
Gen ID (AID) / Gen ID (AID) 8 8 100.0%
Genomica / Genomica 1 1a 100.0%
Greiner / Greiner 9 9 100.0%
Innogenetics / Innogenetics 15 15b, c
100.0%
Roche / Roche 12 12 100.0%
in house / Roche 1 1 100.0%
in house / in house 1 1 100.0%
in house / other manufacturer 1 1 100.0%
other manufacturer / other manufact. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
andere PCR / hybridization (9870)
astra Diag. / astra Diag. 1 1d
0.0% a One participant detected additionally HPV type 45.
b One participant detected additionally HPV type 39, HPV type 68 and HPV type 73.
c One participant detected additionally HPV type 39.
d The sample 373011 comprises exclusively "High Risk" HPV type 18. Therefore the reporting of "Low Risk" HPV type 42,
HPV type 43 and HPV type 44 was assessed as "incorrect" result.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 3
Results for sample 373011
30. Typing of HPV (continued)
method / manufacturer total type
HPV 18 other type
below level of detection/ negative/ not stated
correct
results
%
sequencing (72) 13 13 0 0 100.0%
PCR / sequencing (1172)
in house / in house 8 8 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manufacturer / other manufact. 1 1 100.0%
other test (99) 6 6 0 0 100.0%
PCR / other test (1199)
AmpliSens / AmpliSens 1 1 100.0%
in house / in house 4 4 100.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
Results for sample 373011
35. Typing of "High Risk" HPV (without determination of "Low Risk" HPV)
(Tests for exclusive detection and typing of "High Risk"-HPV )*
Correct result: HPV 18
test results in total total type
HPV 18 other type
below level of detection/ negative/
not stated*
correct
results
%
8 8 0 0 100.0%
method / manufacturer total type
HPV 18 other type
below level of detection/ negative/
not stated*
correct
results
%
hybridization (70) 7 7 0 0 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
other test (99) 1 1 0 0 100.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
* These tests exclusively detect and type "High Risk"-HPV and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 4
Results for sample 373011
60. Determination of "High Risk" HPV (without determination of "Low Risk" HPV) (Tests which exclusively detect "High Risk"-HPV)*
Correct result: High Risk
test results in total total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
18 17 0 0 1 94.4%
method / manufacturer total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
hybridization (70) 16 16 0 0 0 100.0%
PCR / hybridization (1170)
Roche / Roche 2 2 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
hybridization / hybridization (3070)
Qiagen / Qiagen 7 7 100.0%
other test (99) 2 1 0 0 1 50.0%
PCR / other test (1199)
other manuf. / other manuf. 1 1 0.0%
TMA / other test (6099)
Gen-Probe / Gen-Probe 1 1 100.0%
* These tests exclusively detect "High Risk"-HPV (without specification of the HPV type) and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 5
Results for sample 373012
20. Differentiation between "High Risk" and "Low Risk" HPV
Correct result: High Risk
test results in total total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
evaluated results
results without evaluation#
hybridization (70)#
hybridization / hybridization (3070) #
Qiagen / Qiagen #
62
30#
30#
57
2#
2#
0
0#
1
2#
2#
4
26#
26#
91.9%
method / manufacturer total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
hybridization (70) 46 43 0 0 3 93.5%
PCR / hybridization (1170)
Chipron / Chipron 3 3 100.0%
Gen ID (AID) / Gen ID (AID) 12 10 2 83.3%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 4 4 100.0%
Innogenetics / Innogenetics 10 10 100.0%
Roche / Roche 6 6 100.0%
in house / Qiagen 1 1 100.0%
in house / Roche 1 1 100.0%
in house / other manuf. 1 1 100.0%
other manuf. / other manuf. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 4 4 100.0%
other PCR / hybridization (9870)
astra Diag. / astra Diag. 1 1 0.0%
sequencing (72) 11 11 0 0 0 100.0%
PCR / sequencing (1172)
in house / in house 6 6 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manuf. / other manuf. 1 1 100.0%
other test (99) 5 3 0 1 1 60.0%
PCR / other test (1199)
in house / in house 4 2 1 1 50.0%
nested PCR / other test (1299)
in house / in house 1 1 100.0%
# Results without evaluation: please see comment to sample 373012.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 6
Results for sample 373012
25. Typing of "High Risk" HPV and detection of "Low Risk" HPV (without typing)
Correct result: HPV 16
test results in total total type
HPV 16 other type
below level of detection/ negative
correct
results
%
7 7 0 0 100.0%
method / manufacturer total type
HPV 16 other type
below level of detection/ negative
correct
results
%
hybridization (70) 5 5 0 0 100.0%
PCR / hybridization (1170)
Gen ID (AID) / Gen ID (AID) 5 5 100.0%
other test (99) 2 2 0 0 100.0%
PCR / other test (1199)
in house / in house 1 1 100.0%
LightCycler / other test (4099)
in house / in house 1 1 100.0%
Results for sample 373012
30. Typing of HPV
Correct result: HPV 16
test results in total total type
HPV 16 other type
below level of detection/ negative/ not stated
correct
results
%
77 71 0 6 92.2%
method / manufacturer total type
HPV 16 other type
below level of detection/ negative/ not stated
correct
results
%
hybridization (70) 58 55 0 3 94.8%
PCR / hybridization (1170)
Chipron / Chipron 7 7
100.0%
Gen ID (AID) / Gen ID (AID) 8 6 2 75.0%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 9 9 100.0%
Innogenetics / Innogenetics 15 15 100.0%
Roche / Roche 12 12 100.0%
in house / Roche 1 1 100.0%
in house / in house 1 1 100.0%
in house / other manufacturer 1 1 100.0%
other manufacturer / other manufact. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
andere PCR / hybridization (9870)
astra Diag. / astra Diag. 1 1 0.0%
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 7
Results for sample 373012
30. Typing of HPV (continued)
method / manufacturer total type
HPV 18 other type
below level of detection/ negative/ not stated
correct
results
%
sequencing (72) 13 13 0 0 100.0%
PCR / sequencing (1172)
100.0%
in house / in house 8 8 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manufacturer / other manufact. 1 1 100.0%
other test (99) 6 3 0 3 50.0%
PCR / other test (1199)
AmpliSens / AmpliSens 1 1 100.0%
in house / in house 4 1 3 25.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
Results for sample 373012
35. Typing of "High Risk" HPV (without determination of "Low Risk" HPV)
(Tests for exclusive detection and typing of "High Risk"-HPV )*
Correct result: HPV 16
test results in total total type
HPV 16 other type
below level of detection/ negative/
not stated*
correct
results
%
8 8 0 0 100.0%
method / manufacturer total type
HPV 16 other type
below level of detection/ negative/
not stated*
correct
results
%
hybridization (70) 7 7 0 0 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
other test (99) 1 1 0 0 100.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
* These tests exclusively detect and type "High Risk"-HPV and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 8
Results for sample 373012
60. Determination of "High Risk" HPV (without determination of "Low Risk" HPV) (Tests which exclusively detect "High Risk"-HPV)*
Correct result: High Risk
test results in total total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
evaluated results
results without evaluation#
hybridization (70)#
hybridization / hybridization (3070) #
Qiagen / Qiagen #
11
7#
7#
11
3#
3#
0
0#
0
0#
0
4#
4#
100.0%
method / manufacturer total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
hybridization (70) 9 9 0 0 0 100.0%
PCR / hybridization (1170)
Roche / Roche 2 2 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
other test (99) 2 2 0 0 0 100.0%
PCR / other test (1199)
other manuf. / other manuf. 1 1 100.0%
TMA / other test (6099)
Gen-Probe / Gen-Probe 1 1 100.0%
* These tests exclusively detect "High Risk"-HPV (without specification of the HPV type) and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
# Results without evaluation: please see comment to sample 373012.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 9
Results for sample 373013
20. Differentiation between "High Risk" and "Low Risk" HPV
Correct result: Low Risk
test results in total total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
92 0 90 0 2 97.8%
method / manufacturer total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
hybridization (70) 75 0 73 0 2 97.3%
PCR / hybridization (1170)
Chipron / Chipron 3 3 100.0%
Gen ID (AID) / Gen ID (AID) 12 11 1 91.7%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 4 4 100.0%
Innogenetics / Innogenetics 10 10 100.0%
Roche / Roche 6 6 100.0%
in house / Qiagen 1 1 100.0%
in house / Roche 1 1 100.0%
in house / other manuf. 1 1 100.0%
other manuf. / other manuf. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
TaqMan / hybridization (1370)
astra Diag. / astra Diag. 1 1 100.0%
hybridization / hybridization (3070)
Qiagen / Qiagen 30 29 1 96.7%
other PCR / hybridization (9870)
astra Diag. / astra Diag. 3 3 100.0%
sequencing (72) 12 0 12 0 0 100.0%
PCR / sequencing (1172)
in house / in house 7 7 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manuf. / other manuf. 1 1 100.0%
other test (99) 5 0 5 0 0 100.0%
PCR / other test (1199)
in house / in house 4 4 100.0%
nested PCR / other test (1299)
in house / in house 1 1 100.0%
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 10
Results for sample 373013
25. Typing of "High Risk" HPV and detection of "Low Risk" HPV (without typing)
Correct result: Low Risk
test results in total total type
HPV 18 other type
below level of detection/ negative
correct
results
%
7 7 0 0 100.0%
method / manufacturer total type
HPV 18 other type
below level of detection/ negative
correct
results
%
hybridization (70) 5 5 0 0 100.0%
PCR / hybridization (1170)
Gen ID (AID) / Gen ID (AID) 5 5 100.0%
other test (99) 2 2 0 0 100.0%
PCR / other test (1199)
in house / in house 1 1 100.0%
LightCycler / other test (4099)
in house / in house 1 1 100.0%
Results for sample 373013
30. Typing of HPV
Correct result: HPV 6
test results in total total type
HPV 6 other type
below level of detection/ negative/ not stated
correct
results
%
78 78 0 0 100.0%
method / manufacturer total type
HPV 6 other type
below level of detection/ negative/ not stated
correct
results
%
hybridization (70) 60 60 0 0 100.0%
PCR / hybridization (1170)
Chipron / Chipron 7 7a
100.0%
Gen ID (AID) / Gen ID (AID) 8 8 100.0%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 9 9a
100.0%
Innogenetics / Innogenetics 15 15a
100.0%
Roche / Roche 13 13 100.0%
in house / Roche 1 1 100.0%
in house / in house 1 1 100.0%
in house / other manufacturer 1 1 100.0%
other manufacturer / other manufact. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
andere PCR / hybridization (9870)
astra Diag. / astra Diag. 2 2a
100.0%
a In total 11 participants detected additionally HPV type 11.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 11
Results for sample 373013
30. Typing of HPV (continued)
method / manufacturer total type
HPV 6 other type
below level of detection/ negative/ not stated
correct
results
%
sequencing (72) 13 13 0 0 100.0%
PCR / sequencing (1172)
in house / in house 8 8 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manufacturer / other manufact. 1 1 100.0%
other test (99) 5 5 0 0 100.0%
PCR / other test (1199)
AmpliSens / AmpliSens 1 1 100.0%
in house / in house 4 4 100.0%
Results for sample 373013
35. Typing of "High Risk" HPV (without determination of "Low Risk" HPV)
(Tests for exclusive detection and typing of "High Risk"-HPV )*
Correct result: negative for "High Risk" HPV
test results in total total type
HPV 6 other type
below level of detection/ negative/
not stated*
correct
results
%
7 0 0 7 100.0%
method / manufacturer total type
HPV 6 other type
below level of detection/ negative/
not stated*
correct
results
%
hybridization (70) 6 0 0 6 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 6 6 100.0%
other test (99) 1 0 0 1 100.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
* These tests exclusively detect and type "High Risk"-HPV and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 12
Results for sample 373013
60. Determination of "High Risk" HPV (without determination of "Low Risk" HPV) (Tests which exclusively detect "High Risk"-HPV)*
Correct result: negative for "High Risk" HPV
test results in total total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
18 1 0 0 17 94.4%
method / manufacturer total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
hybridization (70) 16 1 0 0 15 93.8%
PCR / hybridization (1170)
Roche / Roche 2 1 1 50.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
hybridization / hybridization (3070)
Qiagen / Qiagen 7 7 100.0%
other test (99) 2 0 0 0 2 100.0%
PCR / other test (1199)
other manuf. / other manuf. 1 1 100.0%
TMA / other test (6099)
Gen-Probe / Gen-Probe 1 1 100.0%
* These tests exclusively detect "High Risk"-HPV (without specification of the HPV type) and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 13
Results for sample 373014
20. Differentiation between "High Risk" and "Low Risk" HPV
Correct result: High Risk
test results in total total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
92 87 1 1 3 94.6%
method / manufacturer total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
hybridization (70) 76 71 1 1 3 93.4%
PCR / hybridization (1170)
Chipron / Chipron 3 3 100.0%
Gen ID (AID) / Gen ID (AID) 12 11 1 91.7%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 4 4 100.0%
Innogenetics / Innogenetics 10 10 100.0%
Roche / Roche 6 5 1 83.3%
in house / Qiagen 1 1 100.0%
in house / Roche 1 1 100.0%
in house / other manuf. 1 1 100.0%
other manuf. / other manuf. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 4 4 100.0%
hybridization / hybridization (3070)
Qiagen / Qiagen 30 28 2 93.3%
other PCR / hybridization (9870)
astra Diag. / astra Diag. 1 1 0.0%
sequencing (72) 11 11 0 0 0 100.0%
PCR / sequencing (1172)
in house / in house 6 6 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manuf. / other manuf. 1 1 100.0%
other test (99) 5 5 0 0 0 100.0%
PCR / other test (1199)
in house / in house 4 4 100.0%
nested PCR / other test (1299)
in house / in house 1 1 100.0%
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 14
Results for sample 373014
25. Typing of "High Risk" HPV and detection of "Low Risk" HPV (without typing)
Correct result: HPV 18
test results in total total type
HPV 18 other type
below level of detection/ negative
correct
results
%
7 7 0 0 100.0%
method / manufacturer total type
HPV 18 other type
below level of detection/ negative
correct
results
%
hybridization (70) 5 5 0 0 100.0%
PCR / hybridization (1170)
Gen ID (AID) / Gen ID (AID) 5 5 100.0%
other test (99) 2 2 0 0 100.0%
PCR / other test (1199)
in house / in house 1 1 100.0%
LightCycler / other test (4099)
in house / in house 1 1 100.0%
Results for sample 373014
30. Typing of HPV
Correct result: HPV 18
test results in total total type
HPV 18 other type
below level of detection/ negative/ not stated
correct
results
%
77 75 1 1 97.4%
method / manufacturer total type
HPV 18 other type
below level of detection/ negative/ not stated
correct
results
%
hybridization (70) 58 56 1 1 96.6%
PCR / hybridization (1170)
Chipron / Chipron 7 7 100.0%
Gen ID (AID) / Gen ID (AID) 8 8 100.0%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 9 9 100.0%
Innogenetics / Innogenetics 15 15a, b
100.0%
Roche / Roche 12 11 1 91.7%
in house / Roche 1 1 100.0%
in house / in house 1 1 100.0%
in house / other manufacturer 1 1 100.0%
other manufacturer / other manufact. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
andere PCR / hybridization (9870)
astra Diag. / astra Diag. 1 1c
0.0%
a One participant detected additionally HPV type 39, HPV type 68 and HPV type 73.
b One participant detected additionally HPV type 39.
c Sample 373014 comprises exclusively "High Risk" HPV type 18. Therefore the reporting of "Low Risk" HPV type 42,
HPV type 43 and HPV type 44 was assessed as "incorrect" result.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 15
Results for sample 373014
30. Typing of HPV (continued)
method / manufacturer total type
HPV 18 other type
below level of detection/ negative/ not stated
correct
results
%
sequencing (72) 13 13 0 0 100.0%
PCR / sequencing (1172)
100.0%
in house / in house 8 8 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manufacturer / other manufact. 1 1 100.0%
other test (99) 6 6 0 0 100.0%
PCR / other test (1199)
AmpliSens / AmpliSens 1 1 100.0%
in house / in house 4 4 100.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
Results for sample 373014
35. Typing of "High Risk" HPV (without determination of "Low Risk" HPV)
(Tests for exclusive detection and typing of "High Risk"-HPV )*
Correct result: HPV 18
test results in total total type
HPV 18 other type
below level of detection/ negative/
not stated*
correct
results
%
8 8 0 0 100.0%
method / manufacturer total type
HPV 18 other type
below level of detection/ negative/
not stated*
correct
results
%
hybridization (70) 7 7 0 0 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
other test (99) 1 1 0 0 100.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
* These tests exclusively detect and type "High Risk"-HPV and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 16
Results for sample 373014
60. Determination of "High Risk" HPV (without determination of "Low Risk" HPV) (Tests which exclusively detect "High Risk"-HPV)*
Correct result: High Risk
test results in total total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
18 18 0 0 0 100.0%
method / manufacturer total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
hybridization (70) 16 16 0 0 0 100.0%
PCR / hybridization (1170)
Roche / Roche 2 2 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
hybridization / hybridization (3070)
Qiagen / Qiagen 7 7 100.0%
other test (99) 2 2 0 0 0 100.0%
PCR / other test (1199)
other manuf. / other manuf. 1 1 100.0%
TMA / other test (6099)
Gen-Probe / Gen-Probe 1 1 100.0%
* These tests exclusively detect "High Risk"-HPV (without specification of the HPV type) and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 17
Results for sample 373015
20. Differentiation between "High Risk" and "Low Risk" HPV
Correct result: negative
test results in total total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
92 0 0 1 91 98.9%
method / manufacturer total High Risk Low Risk indeterminate below level of
detection/ negative
correct
results
%
hybridization (70) 76 0 0 1 75 98.7%
PCR / hybridization (1170)
Chipron / Chipron 3 3 100.0%
Gen ID (AID) / Gen ID (AID) 12 1 11 91.7%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 4 4 100.0%
Innogenetics / Innogenetics 10 10 100.0%
Roche / Roche 6 6 100.0%
in house / Qiagen 1 1 100.0%
in house / Roche 1 1 100.0%
in house / other manuf. 1 1 100.0%
other manuf. / other manuf. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 4 4 100.0%
hybridization / hybridization (3070)
Qiagen / Qiagen 30 30 100.0%
other PCR / hybridization (9870)
astra Diag. / astra Diag. 1 1 100.0%
sequencing (72) 11 0 0 0 11 100.0%
PCR / sequencing (1172)
in house / in house 6 6 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manuf. / other manuf. 1 1 100.0%
other test (99) 5 0 0 0 5 100.0%
PCR / other test (1199)
in house / in house 4 4 100.0%
nested PCR / other test (1299)
in house / in house 1 1 100.0%
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 18
Results for sample 373015
25. Typing of "High Risk" HPV and detection of "Low Risk" HPV (without typing)
Correct result: negative, not done
test results in total total type other type
below level of detection/ negative / not done
correct
results
%
7 0 0 7 100.0%
method / manufacturer total type other type
below level of detection/ negative/ not done
correct
results
%
hybridization (70) 5 0 0 5 100.0%
PCR / hybridization (1170)
Gen ID (AID) / Gen ID (AID) 5 5 100.0%
other test (99) 2 0 0 2 100.0%
PCR / other test (1199)
in house / in house 1 1 100.0%
LightCycler / other test (4099)
in house / in house 1 1 100.0%
Results for sample 373015
30. Typing of HPV
Correct result: negative, not done
test results in total total type other type
below level of detection/ negative/ not done
correct
results
%
77 0 0 76 98.7%
method / manufacturer total type other type
below level of detection/ negative/ not done
correct
results
%
hybridization (70) 58 0 0 57 98.3%
PCR / hybridization (1170)
Chipron / Chipron 7
7 100.0%
Gen ID (AID) / Gen ID (AID) 8 7a 87.5%
Genomica / Genomica 1 1 100.0%
Greiner / Greiner 9 9 100.0%
Innogenetics / Innogenetics 15 15 100.0%
Roche / Roche 12 12 100.0%
in house / Roche 1 1 100.0%
in house / in house 1 1 100.0%
in house / other manufacturer 1 1 100.0%
other manufacturer / other manufact. 1 1 100.0%
nested PCR / hybridization (1270)
in house / in house 1 1 100.0%
andere PCR / hybridization (9870)
astra Diag. / astra Diag. 1 1 100.0%
a One participant did not report any result for sample 373015.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 19
Results for sample 373015
30. Typing of HPV (continued)
method / manufacturer total type other type
below level of detection/ negative/ not stated
correct
results
%
sequencing (72) 13 0 0 13 100.0%
PCR / sequencing (1172)
in house / in house 8 8 100.0%
nested PCR / sequencing (1272)
in house / in house 4 4 100.0%
TaqMan / sequencing (1372)
other manufacturer / other manufact. 1 1 100.0%
other test (99) 6 0 0 6 100.0%
PCR / other test (1199)
AmpliSens / AmpliSens 1 1 100.0%
in house / in house 4 4 100.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
Results for sample 373015
35. Typing of "High Risk" HPV (without determination of "Low Risk" HPV)
(Tests for exclusive detection and typing of "High Risk"-HPV )*
Correct result: negative for "High Risk" HPV
test results in total total type other type
below level of detection/ negative/
not stated*
correct
results
%
8 0 0 8 100.0%
method / manufacturer total type other type
below level of detection/ negative/
not stated*
correct
results
%
hybridization (70) 7 0 0 7 100.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
other test (99) 1 0 0 1 100.0%
TaqMan / other test (1399)
Roche / Roche 1 1 100.0%
* These tests exclusively detect and type "High Risk"-HPV and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.
373 Human Papilloma Viruses Genome June July 2011 Table 20110830a.doc 20
Results for sample 373015
60. Determination of "High Risk" HPV (without determination of "Low Risk" HPV) (Tests which exclusively detect "High Risk"-HPV)*
Correct result: negative for "High Risk" HPV
test results in total total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
18 1 0 0 17 94.4%
method / manufacturer total High Risk Low Risk indeterminate below level
of detection/ negative*
correct
results
%
hybridization (70) 16 1 0 0 15 93.8%
PCR / hybridization (1170)
Roche / Roche 2 1 1 50.0%
TaqMan / hybridization (1370)
Abbott / Abbott 7 7 100.0%
hybridization / hybridization (3070)
Qiagen / Qiagen 7 7 100.0%
other test (99) 2 0 0 0 2 100.0%
PCR / other test (1199)
other manuf. / other manuf. 1 1 100.0%
TMA / other test (6099)
Gen-Probe / Gen-Probe 1 1 100.0%
* These tests exclusively detect "High Risk"-HPV (without specification of the HPV type) and cannot detect "Low Risk"-HPV. This means that a negative test result obtained by these tests can only be interpreted as "negative for High Risk-HPV". Results representing "negative for High Risk-HPV" will be stated as "negative" in your statement of individual results.