The number of people suffering from oral or oropharyngeal cancer is rising steadily. The major cause of these cancers is human papillomaviruses (HPV) that colonise the oral cavity, where they are difficult to detect. QIAGEN Lake Constance GmbH from Stockach, in cooperation with Abviris Deutschland GmbH, has developed a new test system to improve the detection of oral HPV. This new system enables rapid and reliable quantitative detection of HPV-specific antibodies outside of a central laboratory and is intended to make it possible in the future to initiate cancer treatment at an early stage.
Long-term consumption of tobacco and alcohol is regarded as one of the primary causes of oropharyngeal and oral cancers. However, over the past few years, an increasing number of patients that do not fall into these risk groups have been diagnosed with these cancers. Research indicates that HPV infections are responsible for the epidemic spread of oral and oropharyngeal cancers in people outside the actual risk group.
Approximately 70 percent of cases of cancers of the tonsils and throat are caused by HPV. The problem with these cancers is that the signs and symptoms are not always obvious to the individual who is developing the cancer. The cancers are also often well hidden in the posterior regions of the oral cavity and are therefore frequently overlooked during routine inspection of the throat, for example during professional tooth cleaning. "So it is all the more important to develop a test system that detects harmful HPV activity rapidly and reliably. This would help us to detect and treat cancers of the oral cavity at a much earlier stage than is currently possible, and so improve patient survival," says Dr. Jörg Schickedanz, General Manager of QIAGEN Lake Constance GmbH.
The company, a subsidiary of QIAGEN N.V., specialises in the development of point-of-need devices for decentralised testing. Such devices enable decentralised analysis and documentation of immunological or molecular tests at the point-of-need, i.e. near the site of patient care. In cooperation with Abviris Deutschland GmbH, QIAGEN has designed a test system that enables quantitative detection of HPV-specific antibodies in blood.
In patients over 40, the presence of HPV antibodies in the blood is highly likely directly related to the presence of a cancerous growth. This is because the immune system is not stimulated by the viruses themselves, but by tumour tissue that has been formed. Following infection of mucosal cells, virus propagation leads to abnormal division of the host cells that line the surface of the mucous membrane. The viruses escape the immune system attack as they do not come into direct contact with immune cells in the blood. The viruses also cause a modification in the cell surface, so immune system dendritic cells cannot recognise the infected cells either. Dendritic cells play a number of crucial roles in detecting abnormal cells and hence inducing an immune response in the killer cells (cytotoxic T cells). Failure to detect abnormal patterns prevents the induction of an immune response, and hence the development of immunity against tumour tissue.
Abviris' rapid lateral flow test Prevo-Check® for detecting HIV-specific antibodies uses a droplet of blood, taken, for example, from the fingertip or earlobe, that is mixed with test buffer and incubated for ten minutes. The mixture is then applied to the lateral flow test strip. "After another ten minutes, the test strip is ready to be optically analysed with QIAGEN's ESEQuant LR3 reader. Depending on the configuration chosen, the ESEQuant LR3 can carry out qualitative or quantitative analyses and either show acquired data on the integrated screen or feed it into a laboratory information system," says Schickedanz.
The new test system will be used in the Hamburg City Health Study (HCHS) for the rapid quantitative detection of HPV-specific antibodies at the point-of-need. HCHS is a comprehensive healthcare study being carried out by the University Medical Centre Hamburg-Eppendorf (UKE).
The aim of HCHS is to identify risk factors for common diseases and develop individualised and focused treatment approaches. The pilot phase started in May 2015, and the main study will begin in November 2015. The study plans to recruit a cohort of 45,000 volunteers aged between 45 and 74, making it the world's largest single-centre study to date. It will run for a period of five years and involve 30 hospitals and UKE institutions working together on an interdisciplinary basis. The participation of the Ear, Nose and Throat Clinic has not previously been possible due to limited resources. It is impossible to carry out pharyngoscopies of 45,000 people within five years with currently available methods. Pharyngoscopies are used to diagnose cancerous lesions in the oropharyngeal cavity at an early stage. "The new Prevo-Chec® test system could potentially change this," says Jörg Schickedanz. The Prevo-Chec® test system can be used to check all volunteers for the presence of HPC-specific antibodies, rapidly and relatively easily. Only patients tested HPV-positive will subsequently undergo pharyngoscopies.
The initial aim of the study is to show that the test system is cost-efficient and easy to use. The next objective is to expand the application of the test system beyond the Hamburg Study. "As oropharyngeal cancers have a high probability of remission, continuous follow-up care of cancer patients is also of paramount importance," says Schickedanz highlighting the need to establish a test system for quantitative detection of HPV antibodies at point-of-need in hospitals and GP surgeries.
In addition to the clinical aspect, there are also other factors that favour examination by a physician. The work of a physician in terms of patient information and pre-analytics is often not adequately reimbursed in Germany. However, if physicians can carry out the test and get paid for it, this might well make them more likely to want to participate in the establishment of cancer screening schemes. "This would be of great benefit for patients who would have a reliable result within a relatively short time, and be able to undergo rapid medical treatment if the test shows positive," concludes Schickedanz.
The test system has huge potential in terms of setting up a new approach to cancer screening. Epidemiological data suggest that the test system will in future make a valuable contribution to early detection of oral and oropharyngeal cancers caused by HP viruses.