|Cervical Cancer||| Print ||
Cervical cancer is the second most common cancer in women worldwide, a position it shares with colorectal cancer - breast cancer being the most prevalent. About 400,000 new cases of cervical cancer are diagnosed each year, with a high proportion occurring among the economically disadvantaged, in both developing and industrialized nations. For the past 50 years, the standard detection method has consisted of the visual inspection of hundreds of thousands of cells per patient (morphology); looking for small changes in the shape and size of cells and nuclei in order to identify pre-cancerous and cancerous cells. This method is referred to as the Pap-Test, after its inventor, Dr G. Papanicolaou, who developed it in the 1940s.
In cervical cancer, early diagnosis is critical for a good prognosis and consequently early detection programs seek to identify both those at risk and those in the very early stages of disease. Worldwide, at least 140 million Pap smears are taken every year. With the implementation of prevention programs for early detection of morphological abnormalities in cervical cells the incidence rate of cervical cancer has decreased by about 70%.
Despite this great success, current early detection technologies and diagnostics for cervical cancer have well recognized limitations resulting in unacceptably rates of false negative, false positive diagnoses and high costs. This is because the tests used currently do not actually detect direct markers of disease resulting in a high degree of subjectivity.
More recently, testing for Human Papillomavirus (HPV) has been adopted for the management of unclear and mildly abnormal Pap Tests (most of which are false positive results). High-risk human papillomaviruses (HR-HPV) have been demonstrated to be the main etiological factor for the development of cervical cancer (see Figure 1). The use of HPV testing for this application is limited to a small percentage of all Pap Tests. HPV testing has superior sensitivity for disease compared to that of a Pap test. However, due to the high rate of HPV infection and prevalence in the general population (up to 30% of women) HPV testing delivers very low specificity (correlation of positive test to actual disease), which severely limits its potential utility to be used for early disease detection.
Figure 1. Persistent infection with high risk HPV over a number of years is known to be causative of cervical cancer.
There is a clinical need for far greater objectivity in early disease detection over the current approaches which rely on subjective, morphological interpretation of cervical cells, or risk assessment based on the presence of HPV. Detecting biomarkers that are specific indicators to the presence or absence of cervical cancer and its precursors represents a more efficient approach to early cervical cancer detection and diagnosis. mtm has identified p16INK4a (p16) as a potential direct marker of the HR-HPV mediated transformation process which is correlated with cervical tissues that have become cancerous or pre-cancerous. mtm's diagnostic kits make use of the clinically validated E6H4™ p16 antibody clone, which is highly selective and sensitive to the presence of p16. Unlike using other clones of p16 antibody, detection with E6H4™ does not show cross reactivity with Trichomonas (a protozoal infection of the vagina). This cross-reactivity renders other p16 antibody clone candidates unacceptable as they may generate too many false positives.
The first of these products, CINtec® Histology has been available on a global basis since January 1, 2007. CINtec PLUS is available in Europe and other countries as a CE marked in vitro diagnostic assay with clinical performance claims since 2010, and in the US for Research Use Only. The GMP manufactured kit components in combination with the optimized antibodies ensure reproducible quality and results in assessing a wide variety of biological specimens.