One of the main challenges to managing the increased incidence of HPV-positive oropharyngeal cancers is correctly diagnosing the disease. Unlike cervical cancer, where all cases are assumed to be HPV-positive, clinicians would like to know which oropharyngeal cancers are driven by HPV and which are not. At present, most institutions are using two tests, either alone or in combination, said Dr. Sturgis, and these are emerging as probable standards.
Explore this issue:November 2012
One test is immunohistochemical analysis of p16 expression levels in tumor tissues, as p16 overexpression appears to be a very specific sign of an HPV-driven oropharyngeal cancer. The second test uses in situ hybridization, which has a high sensitivity to detect many types of oncogenic HPV, and is often used as a confirmatory test if p16 immunohistochemistry is positive.
Caution is urged, however, when using serological testing alone. “We need to be very cautious when people come in with positive HPV DNA results, because the infection in many of these people will clear on its own,” said Dr. D’Souza, who added that “we need to think about whether to do HPV DNA screening and how to counsel people about this type of screening.”
Recently published results of two population-based studies also question the use of serology testing, showing that assessment of HPV DNA alone is a poor biomarker for oropharyngeal cancers caused by HPV. In one multicenter U.S. study, researchers looked at several biomarkers and found that neither HPV DNA positivity nor expression of p16 alone were good predictors of survival outcomes (Cancer Res. 2012;72:5004-5013). Rather, they found that expression of the two oncoproteins E6 and E7, either alone or combined with HPV DNA positivity or p16 expression, were better predictors of survival outcomes. In a second study, German researchers also found poorer survival outcomes predictability with HPV DNA testing and instead found that a high viral load and a cancer-specific pattern of viral gene expression were stronger predictors (Cancer Res. 2012;72:4993-5003).
According to Karl T. Kelsey, MD, professor of epidemiology and pathology and laboratory medicine at Brown University in Providence, R.I. and senior author of the U.S. study, these results indicate a need to revisit the methods used to identify HPV-driven head and neck cancers and to test these methods vigorously. “We need to look at population-based studies, because it is important to study everyone so we can estimate the generalizability of every method to apply these not only in the major academic centers but in the community as well.”
For Dana Holzinger, PhD, a researcher with the Infection and Cancer Program at the German Cancer Research Center in Heidelberg and lead author of the German study, the findings highlight the need to look at other potentially more useful biomarkers, such as viral load and expression patterns, to develop a standard way of identifying HPV-driven head and neck cancers. “Once standardized assays for these markers are established and can be applied in routine clinical laboratories, they will allow precise identification of oropharyngeal cancer patients with or without HPV-driven cancers and thus will influence prognosis and potentially treatment decisions,” she said.