About 45,750 Americans will be diagnosed with oral or pharyngeal cancer this year, according to the Oral Cancer Foundation, and only slightly more than half of them will still be alive 5 years from now.
The low survival rate is due to the disease’s late diagnosis, which often doesn’t happen until it is in stage 3 or 4. The human papillomavirus (HPV) is causing a growing number of cases, so early detection of HPV in the oral cavity could save thousands of lives.
Dr. Jennifer Webster-Cyriaque, a professor in the Department of Dental Ecology at the University of North Carolina School of Dentistry and in the Department of Microbiology and Immunology in the University of North Carolina School of Medicine, is working with InSilixa Inc. to develop a rapid oral HPV test that could play a key role in timely diagnosis and treatment.
“Right now, there isn’t a US Food and Drug Administration-approved test for oral HPV that’s available for point-of-care (POC) testing in the clinical setting,” said Webster-Cyriaque. “So the potential for this test is significant.”
The partnership will use InSilixa’s disposable semiconductor-based biochip technology to adapt a test originally developed in Webster-Cyriaque’s lab so it can detect oral HPV when a patient comes in for care. Patients would swish or gargle a solution, and the clinician would take a sample. That sample would be added to a cartridge that includes the biochip.
“It is really a DNA analysis instrument on a small chip. It uses 32×32 semiconductor-integrated and miniaturized biosensor arrays to detect unique DNA markers of HPV and its high-risk strains electronically,” said Webster-Cyriaque.
The technology can identify hundreds of unique bio-molecule targets, including nucleic acids (DNA or RNA) and peptides, in parallel. By reading these biomarkers in the sample, the biochip can detect the presence of HPV in the oral cavity and then identify and quantify which one of the nearly 200 strains of HPV it is. Some strains present a greater cancer risk than others.
To get the results, the clinician inserts the cartridge into a handheld reader that’s about the size of a large mobile phone. Within an hour, the reader provides a quantitative and qualitative patient report that the clinician would use to identify the strain as well as how much of it is present. Based on this information, the doctor can assess the risk for HPV-induced cancer.
“Persistent, high-risk HPV is the single most important risk factor in progression to an oropharyngeal cancer,” said Webster-Cyriaque. “So if a person came in at point x, a high-risk type, and then came back again at point y, still a high-risk type, we may want to follow that person more closely. We may want to refer them to an oral surgeon or an ear, nose, and throat doctor.”
About 79 million Americans currently have HPV, including 10% of men and 3.6% of women with oral HPV, with about 14 million new infections each year. It is the most common sexually transmitted infection, and nearly all sexually active men and women get it at some point in their lives. Most people with HPV-associated cancers are in their fifties, sixties, and seventies.
“We know that many people have their initial exposure to HPV in their twenties, and many times, people clear the infection,” said Webster-Cyriaque. “Sometimes they don’t, and the virus is able to establish latency. The metrics describing the exact numbers in terms of what percentage of cases that establish latency move forward to become cancer don’t exist yet.”
Despite the prevalence of HPV, this test might not become a standard procedure in routine trips to the dentist for cleanings and exams. For example, tobacco and alcohol use also are risk factors in oral cancer, but not all oral cancer patients smoke or drink. Webster-Cyriaque says more research and epidemiologic studies will help determine which risk factors will drive the criteria for administering the test.
Still, the technology has promise. The National Institutes of Health (NIH) awarded a $224,764 Phase I Small Business Innovation Research Grant to InSilixa to develop the rapid POC molecular diagnostics version of the test. The company also recently received an NIH grant to develop a lab-on-a-chip tuberculosis test. Furthermore, it is working on biochips that can detect upper respiratory infections, HIV viral load/drug resistance, and drug-resistant bacteria associated with hospital-acquired infections.
“The PCR-based (polymerase chain reaction) test that serves as the basis for this POC assay has demonstrated significant specificity and sensitivity,” said Webster-Cyriaque. “This is a test that has been used in National Institute of Dental and Craniofacial Research sponsored clinical trials.”
The researchers believe the test is a vast improvement over current detection methods, which rely on invasive and painful biopsies that often turn out to be negative anyway. The disposable chip also is much less expensive. And most importantly, it finds HPV long before lesions and other abnormalities form.
“The one major issue that we have right now for oral cancer is that it is detected so late. The morbidity and mortality are very high, and that, of course, is associated with higher healthcare costs,” said Webster-Cyriaque. “So prevention or detection of an early lesion would likely save the insurance companies a good amount of money.”