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Study Finds Oral Cancer Prognostic Clues From Spit Samples With Persistent HPV16 DNA

NEW YORK (GenomeWeb) – A study appearing online today in JAMA Oncology suggests spit samples containing DNA from a particular human papillomavirus type may offer clues to oral cancer recurrence and survival.

Researchers from Johns Hopkins University searched for HPV DNA in samples provided by 124 oropharyngeal carcinoma patients who swished out their mouths before treatment, as well as months after treatment. Their results revealed a significant rise in recurrence and related dip in survival time for the minority of individuals with type 16 HPV DNA in spit samples provided after treatment.

"Our data suggest that persistent HPV16 DNA detection in post-treatment oral rinses, although uncommon, is associated with poor prognosis and may be predictive of disease recurrence," corresponding author Gypsyamber D'Souza, an epidemiology researcher at the Johns Hopkins Bloomberg School of Public Health, and her co-authors wrote.

Though additional research is needed, they argued that "HPV16 DNA detection in oral rinses is a potentially useful tool for long-term tumor surveillance for the growing population of [HPV-positive oropharyngeal carcinoma] survivors."

Oropharyngeal squamous cell carcinoma cases involving HPV16 are on the rise in the US, other parts of North America, Western Europe, and Australia. And while HPV-positive oral cancers often respond well to treatment, the researchers explained, between one-tenth and one-quarter of HPV-positive oropharyngeal carcinomas reappear within two years.

In the hopes of finding a reliable strategy for tackling recurrence early, the team scrutinized Scope mouthwash oral rinse samples from 124 individuals diagnosed with HPV-positive oropharyngeal carcinomas between 2009 and 2013.

The same individuals provided spit samples nine months, one year, 18 months, and two years after initial diagnosis and treatment.

When they used PCR-based approaches to target three dozen HPV types, the researchers detected HPV16 DNA in more than half of the pre-treatment samples.

Only six individuals — less than 5 percent of those tested — had HPV16 DNA at levels that could be picked up by PCR in post-treatment oral rinse samples. Of those, five had had HPV16 DNA in diagnostic samples as well.

While less than 8 percent of the individuals without persistent HPV16 DNA developed recurrent oropharyngeal carcinoma, relapse occurred in all five of the individuals who had DNA from the virus in their pre- and post-treatment rinse samples.

Moreover, the team's TaqMan quantitative PCR-based tests hinted that higher HPV16 DNA levels at diagnosis coincide with lower-than-usual overall survival times.

The relationship appeared to be HPV type-specific, though, since seven individuals with type 33, 39, 45, 51, 52, or 59 HPV DNA in post-treatment rinse samples didn't show particularly high recurrence risk.

The researchers cautioned that the HPV16 DNA-based oral rinse assay shows relatively low sensitivity when trying to pick up all recurrence cases, though it seemed to be particularly prone to picking up locally recurrent disease. They noted that it may be possible to bump up sensitivity by folding in complementary markers, including antibodies targeting HPV16.

In a JAMA Oncology commentary, University of Pittsburgh researchers Julie Bauman and Robert Ferris also highlighted the importance of not only improving the test's sensitivity, but also refining its positive predictive value and demonstrating that it picks up surgically treatable tumors.

Nevertheless, the duo noted, "the high negative predictive value of oral rinse HPV16 DNA detection raises the promise of de-intensifying surveillance visits and/or costly imaging, particularly if on a prospective trial."