Every year, 6,500 women are diagnosed with cervical cancer in Germany and 1,800 die from the disease. The number of deaths would be even higher were it not for cancer screening programmes that entitle all women over 20 in Germany to undergo annual testing for the presence of abnormal cervical cells. The mortality resulting from cervical cancer has decreased dramatically in countries offering regular cervical cancer screening programmes. Such a programme has been available in Germany since 1993. Regular screening tests help to detect premalignant (precanceroses) and malignant (cancerous) processes in the cervix as early as possible and put treatment in place immediately. Therefore, the screening procedures enable the early diagnosis of cancer rather than prevention of disease, a differentiation that is important for oncologists. From the patients' perspective, it is the result that matters most, i.e. the ability to prevent the fatal outcome of cervical cancer.

The Pap test (also known as Papanicolaou test or smear test) was developed by the Greek doctor G. N. Papanicolaou and is still one of the most important tools to identify the very early stages of disease in women. Cells are gathered from the outer opening of the cervix of the uterus and the endocervix, fixed, dyed and visually inspected under the microscope by pathologists for abnormalities. The introduction of the test was the beginning of cytodiagnostics being an important screening tool and contributing to the recognition of a strategy of preventive oncology that focuses on the prevention and early detection of cancerous diseases. The Pap test is nowadays regarded as the most successful "cancer test" ever. Millions of women have received the Pap test and deaths from cervical cancer have been greatly reduced because of the test (see below).

Although the Pap test has saved the lives of millions of women, it nevertheless has its weaknesses. “False-negative” findings in which malignant alterations go undetected, and “false-positive” findings in which healthy cells or those that have changed their shape due to other influences are classified as precancerous cells are quite frequent. Repeated examinations can reduce the errors, but usually require a biopsy to substantiate the findings. Biopsies are quite invasive surgical inventions that are carried out every year on around 100,000 women in Germany alone.

After Harald zur Hausen showed that human papilomaviruses (HPV) are the major cause of cervical carcinoma (see BioPro article of 15th March 2010: The first vaccination against cancer), the detection of papilomaviruses in the smear has been discussed as a potential means of detection of cervical cancer. The test focuses on the high-risk human papilomavirus types (HR-HPV), in particular on HPV16 and HPV18 which cause most of the HPV-associated cancer cases. However, this test is of no predictive value in healthy women because, although HPV infection is the cause of nearly all cases of cervical cancer, most infections with these virus types do not cause disease. Fortunately, cancer develops only rarely and it is common that the pathogens disappear naturally.

The test methods developed by mtm laboratories enable a far more accurate diagnosis of precancerous lesions. The patent-protected test kits are based on the company's proprietary E6H4TM antibody clone.  This was specifically developed for immunochemistry applications involving formalin-fixed, paraffin-embedded tissue sections and alcohol-fixed cell preparations. The assay measures the overexpression of the cyclin-dependent kinase inhibitor p16^INK4a, a biomarker that is a direct indicator of the oncogenic activity of HR-HPV. The E6H4TM antibody, whose sensitivity and specificity has been confirmed and validated in more than 50 research studies, is combined in a kit with components manufactured according to GMP (good manufacturing practice) standards to ensure reproducible quality and results.

The company's CINtec® Histology Kit is an immunohistochemistry assay for the qualitative detection of the p16^INK4a antigen on slides prepared from formalin-fixed, paraffin-embedded cervical biopsies. The CINtec® Cytology Kit is used for use of smears and liquid-based cytology preparations. CINtec®PLUS is the company's most advanced screening kit for cervical cancer. It combines the p16 cell cycle regulator with Ki-67, a marker of active cell proliferation. The test combines high sensitivity and high specificity to detecting high-grade disease. As a recent large study has shown, CINtec®PLUS is far superior to the Pap test and HR-HPV testing (Denton KJ et al., Am. J. Clin. Pathol. 134: 12-21, 2010).

The company's Cervatex^TM ELISA is an innovative test for the quantitative determination of p16^INK4a. The test is based on the detection of the p16 biomarker in the cell lysate, which can easily be produced from cervical smears through heating. The Cervatex® ELISA assay is independent from the morphological assessment of cell types and has the potential to revolutionise the early detection of cervical cancer. The assay has been available in Germany since early 2008.