Human papillomavirus (HPV) DNA positivity alone, particularly when assessed using polymerase chain reaction methods, is a poor biomarker for HPV-driven head and neck cancers, according to two studies published in Cancer Research, a journal of the American Association for Cancer Research. These studies identified alternative potential markers including viral load, viral gene expression and the evaluation of HPV DNA in combination with certain HPV assays.
Prior research has established that HPV is a cause of some head and neck cancers, including oropharyngeal cancer, and that patients with HPV-associated disease tend to have a better clinical outcome. Consequently, the proper assessment of the clinical status of individual tumors has become a goal of clinicians treating this disease because HPV at the tumor site does not indicate causal involvement in the cancer.
In the first study, Dana Holzinger, Ph.D., of the division of genome modifications and carcinogenesis at the German Cancer Research Center in Heidelberg, Germany, and colleagues analyzed the potential of direct and indirect HPV markers to identify patients with HPV-driven tumors.
They analyzed 199 oropharyngeal squamous cell carcinoma specimens for HPV DNA, viral load, RNA expression patterns seen in cervical carcinomas and the p16 protein, which is associated with tumor suppression.
Results indicated that the cervical cancer RNA expression pattern and viral load were associated with the lowest risk for death from oropharyngeal cancer. In contrast, a weaker association was found for samples that were HPV DNA-positive or that expressed the p16 protein.
“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,” Holzinger said. “Viral expression pattern is a completely new marker in this field and viral load has hardly been analyzed before.”
In a second study, researchers evaluated several biomarkers individually and in combination for overall survival among head and neck cancers including polymerase chain reaction-based and serological HPV DNA testing, and p16 immunohistochemistry.
They found that the expression of two oncoproteins, E6 and E7, was associated with improved survival in oropharyngeal disease. In addition, HPV DNA positivity or p16 expression combined with E6 and E7 expression were also associated with enhanced survival. However, neither HPV DNA positivity nor expression of p16 alone yielded a similar result.
“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,” said study author Karl T. Kelsey, M.D., professor in the department of epidemiology and the department of pathology and laboratory medicine at Brown University in Providence, R.I. “We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments.”
The next step in this research is further validating the findings of these two studies using head-to-head comparisons and developing assays for direct clinical application of the markers.
“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,” Holzinger said.