September 19, 2012
Combination HPV Tests Better Than Viral DNA Test Alone For Detecting Certain Cancers
Connie K. Ho for redOrbit.com — Your Universe Online
Two new studies published in the journal of the American Association for Cancer Research discovered that assessments of the human papillomavirus (HPV) that test for a single DNA biomarker alone are a weak indicator for determining the risk of HPV-driven head and neck cancers. On the other hand, the studies point to a combination of genetic markers that may provide a more robust test.
In these new studies, researchers were able to determine possible alternative markers such as viral load, viral gene expression and the evaluation of HPV DNA with specific HPV analyses. Viral load refers to the amount of virus present in a specific quantity of body fluid, while viral gene expression simply indicates which genes on a virus´ DNA or RNA are actually being produced and in what quantities.
"We showed that high viral load and a cancer-specific pattern of viral gene expression are most suited to identify patients with HPV-driven tumors among patients with oropharyngeal cancer," explained Dana Holzinger, a researcher in the Division of Gene Modifications and Carcinogenesis at the German Cancer Research Institute, in a prepared statement.
"Viral expression pattern is a completely new marker in this field and viral load has hardly been analyzed before."
The scientists determined that not all cancers were created equally, with cancers related to infections of HPV being weaker than other carcinogens like smoking. The data was collected from patients in the Boston area and tracked since late 1999. Researchers both studied blood serology and tumor samples as well as interviewed participants on past behaviors like drinking and smoking.
In one study study, the team of investigators analyzed the effectiveness of direct and indirect HPV to pinpoint patients who had HPV-driven tumors. They looked at 199 oropharyngeal squamous cell carcinoma specimens for HPV DNA, RNA expression patterns and viral load that were associated with cervical carcinomas and the so-called p16 protein, which is associated with the suppression of tumors.
The researchers discovered that cervical cancer RNA expression patterns and viral load were related to the lowest risk for death from oropharyngeal cancer, but there was a weaker association for samples that expressed the p16 protein or were HPV DNA-positive.
So what does all this mean in practical terms?
“Everybody who has studied it has shown that people with virally associated disease do better," explained Karl Kelsey, co-author of the study in Cancer Research.
"There are now clinical trials underway to determine if they should be treated differently. The problem is that you need to appropriately diagnose virally related disease, and our data suggests that people need to take a close look at that."
In a second study, the researchers evaluated different biomarkers individually as well as looked for head and neck cancers that had survived individually. Two oncoproteins, E6 and E7, were found to be related to improved survival in oropharyngeal disease. Additionally, HPV DNA positivity or p16 expression added with E6 and E7 expression could increase the chance of survival. When HPV DNA was positive and p16 were expressed alone, they did not show the same results.
"Assessment of HPV DNA using polymerase chain reaction methods as a biomarker in individual head and neck cancers is a poor predictor of outcome and is also poorly associated with antibody response indicative of exposure and/or infection by HPV," remarked Kelsey, a professor in the Brown University Department of Epidemiology as well as the Department of Pathology and Laboratory Medicine.
"We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments."
In moving forward with the findings, the team of investigators plans to conduct more research to validate the results of the two studies with head-to-head comparisons as well as to design assays for the biomarkers that may have direct clinical applications.
"Once standardized assays for these markers, applicable in routine clinical laboratories, are established, they will allow precise identification of patients with oropharyngeal cancer with or without HPV-driven cancers and, thus, will influence prognosis and potentially treatment decisions," concluded Holzinger in the statement.