EEMAPS study shows mtm’s p16/Ki-67 dual immuno-staining superior to Pap and HPV testing for identifying high-grade cervical disease in ASC-US and LSIL
Study results presented at ICC, Edinburgh 16-20 May 2010

Heidelberg, Germany- May 18, 2010-mtm laboratories today announced the presentation of a study showing that dual staining for p16 and Ki-67 can pinpoint the underlying high-grade cervical disease with a high degree of sensitivity and specificity in women with ASC-US or LSIL cytology results. This study used the advanced biomarker combination CINtec® PLUS that was launched by mtm on March 8 2010 in Europe and the full results will be presented today at the 17th International Congress of Cytology, Edinburgh.

ASC-US and LSIL define equivocal and mild to moderate abnormal cytology findings on Pap tests, and may represent 5-8% of all cervical cytology cases. While most of these findings are negative for high-grade disease, 15-20% of LSIL and 6-10% of ASC-US will harbour high-grade disease. Together, these two categories of cytology represent the source for about 60% of all cases of high-grade cervical disease in women. Unfortunately, due to the low rates of underlying disease these Pap cytology results are not adequate predictors to determine which ASC-US or LSIL cases require intervention. In addition, adjunctive HPV testing has limitations due to poor specificity.

In the EEMAPS study, residual materials from a previous pan-European retrospective cytology study were used to prepare additional slides for p16 and Ki-67 dual immuno-staining. A total of 362 ASC-US and 415 LSIL cases with corresponding biopsy results and HPV test results were available for analysis. The presence of one or more dual-stained cervical epithelial cell(s) defined a positive test result with CINtec® PLUS , independent from morphology interpretation. The clinical results showed that the sensitivity of the dual stain for high-grade disease was 92.2% (71/77) for ASC-US, and 94.2% (129/137) for LSIL cases, which is equivalent to the sensitivity results obtained for HPV testing. However, specificity was significantly higher for CINtec® PLUS as compared to HPV testing; 80.6% vs. 36.3% for ASC-US and 68.0% vs. 19.1% for LSIL. CINtec® PLUS is the first test that provides high sensitivity and high specificity for underlying high-grade cervical disease in a single product, irrespective of women’s age and HR-HPV type of infection.

Bob Silverman, CEO of mtm laboratories commented:
“EEMAPS demonstrates that CINtec® PLUS can accurately identify the women that most require follow up in screening just where Pap cytology and HPV testing have insufficient specificity. Using p16/Ki-67 dual immuno-staining alongside Pap for ASC-US and LSIL results will significantly reduce the number of women needing unnecessary follow up and focus resources on identifying those women who have established high-grade cervical disease. This indicates that CINtec® PLUS can be particularly useful in improving current ASC-US triage algorithms and for the first time provide a triage option for women with LSIL cytology result.”

The title and authors of the presentation are as follows:

HIGH SENSITIVITY AND HIGH SPECIFICITY FOR CIN2+ OF p16/Ki-67 DUAL STAINED CYTOLOGY IN THE TRIAGE OF ASC-US AND LSIL: RESULTS FROM THE EEMAPS STUDY
D Schmidt, C Bergeron, KJ Denton, R Ridder. Institute for Pathology, Mannheim, Germany;  Laboratoire Cerba, Cergy Pontoise, France; Department of Cellular Pathology, Southmead Hospital, Bristol, UK; mtm laboratories, Heidelberg, Germany


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About mtm laboratories AG
mtm laboratories AG is an ISO 9001 and ISO 13485 certified developer and manufacturer of In-Vitro Diagnostic Devices (IVDD) for use in the early detection and diagnosis of cervical cancer. The Company operates on a global basis with headquarters in Heidelberg, Germany and subsidiaries in the United States, France, Italy and Spain. Further information can be found at: www.mtmlabs.com

In the US the product is available as a Class 1 IVD without claims. The utility as described in this press release and as investigated in the cited study have not been cleared or approved by the United States Federal Food and Drug Administration.


Further Information:
Bob Silverman
CEO
mtm laboratories AG
t: +1 508-366-8334
e: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Dr. Douglas Pretsell
Associate Partner
College Hill
t : +49 (0)89 57 00 18 06
e: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Notes for editors

Classification of Cervical Cytology
The Pap smear classifications are related to the nature of the cells sampled from the cervix showing single cells or groups of cells. The most recent classification is the Bethesda system, which divides the results of the morphologic interpretation into four main groups:
1)    Cervical specimens negative for intra-epithelial lesions or malignancies (NILM) – cases with morphological interpretation within normal limits
2)    Atypical Squamous Cells of Undetermined Significance (ASC-US) - cases with no definitive cellular abnormality but enough suspicion to keep the case from being considered “normal” (this is an ambiguous category)
3)    Low-grade Squamous Intraepithelial Lesion (LSIL)
4)    High-grade Squamous Intraepithelial Lesion (HSIL)
Broadly speaking LSIL corresponds to mild to moderate pre-cancerous disease and HSIL corresponds to high-grade pre-cancerous disease. Screening with cytology provides an indicator to the physician that something may be wrong with a woman’s cervix and can be used to direct this patient towards further evaluation (eg colposcopy).

CINtec® PLUS
CINtec® PLUS is a screening and diagnostic tool combining high sensitivity and high specificity for detecting high-grade cervical disease in a single test. The CINtec® PLUS kit detects and stains for two biomarkers: the multiply validated cell cycle regulatory protein p16INK4a (p16) and Ki-67, a marker of active cell proliferation. Clinical trials involving over 32,000 women have demonstrated that when used together, this biomarker combination is both highly sensitive and highly specific to identify those women most likely to have existing high–grade disease. Moreover, the CINtec® PLUS test is independent of age and HR-HPV type of infection.

Applied in combination the co-detection of p16 plus Ki-67 in the same cell serves as an indicator of cell cycle de-regulation that occurs during HR-HPV induced oncogenic transformation and provides an objective criterion to identify those women who are likely to harbour high-grade disease. CINtec® PLUS can be applied on conventional and liquid based cytology slides. Double immuno-reactive (or: Dual-stained) cells in cytology are positively stained for both proteins:
•    Brown cellular staining indicates p16 over-expression
•    Red nuclear staining indicates Ki-67 expression