A Janus G3 Automated Workstation at the Cancer Genomics Research Laboratory, one of the instruments used to conduct the TypeSeq assay.
Published:
11/15/2019

FREDERICK, Md. -- Scientists at the Frederick National Laboratory for Cancer Research, the National Cancer Institute, and other collaborating institutions have demonstrated that their recently developed technique for detecting human papillomavirus (HPV) in patient samples performs comparably to existing gold-standard methods.

The group validated the technique, an assay known as TypeSeq, and published the results in the Journal of Infectious Diseases. According to the study, there were few significant differences between TypeSeq’s performance and that of two major HPV-detection assays, Linear Array and SPF10-LiPA.

HPV is a family of more than 200 sexually transmitted viruses, about 18 of which can cause cancer. Most people who contract HPV are unaware and exhibit no symptoms, so improved, accessible detection methods are critical for cancer-prevention efforts.

TypeSeq was developed at the Frederick National Laboratory’s Cancer Genomics Research Laboratory in collaboration with the National Cancer Institute. Last year, the national laboratory made it available to external users at cost through a technical service agreement.

Now, their study shows that TypeSeq is well-suited for use in laboratory settings, which is promising because the assay can challenge existing gold-standard assays’ delivery times and costs. Using next-generation sequencing, a fast and high-capacity method for examining DNA, TypeSeq can simultaneously screen 950 samples for more than 50 strains of HPV, including several cancer-causing ones, in just three days at roughly $24 per sample.

“It really is a gamechanger for a lot of our work here and also for the outside world,” said Nicolas Wentzensen, M.D., Ph.D., senior investigator and deputy branch chief in the National Cancer Institute’s Division of Cancer Epidemiology and Genetics, who helped to develop TypeSeq and author the study.

Wentzensen added that TypeSeq’s comparability to the gold-standard assays could help researchers overcome those assays’ limitations posed by effort and cost.

TypeSeq detects more HPV genotypes than Linear Array and SPF10-LiPA, giving its users a broader picture of those present in a patient. It’s also designed for use on most existing next-generation sequencing platforms, says study author Sarah Wagner, lead TypeSeq developer and lead scientist in the Cancer Genomics Research Laboratory, which makes it accessible to users with diverse technological capabilities. This is especially important given that the highest rates of HPV infection are often found in resource-limited and less-developed countries that have the greatest need for flexible, affordable, and large-scale screening methods.

“It’s highly adaptable to new equipment,” Wagner added, pointing out that TypeSeq will remain usable on future sequencing platforms.

To validate the assay, the scientists used TypeSeq to screen more than 5,000 cervical cell samples previously provided by women participating in two large HPV clinical trials and compared the results to data previously collected using Linear Array and SPF10-LiPA.

TypeSeq detected the presence of HPV with sensitivity similar to the other assays. Larger discrepancies existed for some genotypes, but most were caused by TypeSeq’s higher sensitivity in detecting certain viral types.

TypeSeq also matched SPF10-LiPA’s ability to measure HPV vaccine efficacy in samples from one trial that examined how well a vaccine protected women from the virus. (There was no comparison with Linear Array because that assay was not used to screen those samples.)

“Measuring HPV in these studies is absolutely crucial, both for understanding the biology but also for, more recently, estimating HPV vaccine efficacy and evaluating the clinical use of HPV genotyping in screening and early detection,” Wentzensen said.

Joseph Boland, the Cancer Genomics Research Laboratory’s research director, confirmed that the team is investigating ways to optimize TypeSeq further but couldn’t offer details at this time. However, he said that the team has enjoyed working with its collaborators and looks forward to doing so in the future.

“We were not a viral genetics laboratory. This was kind of our first foray into that. Really, it was just a collaboration of colleagues and friends who put our heads together to solve a problem,” he said.

Studies are underway to examine TypeSeq’s ability to detect HPV in samples from other bodily sites where infections can exist, such as the anus, mouth, and throat. If they succeed, their findings will expand the assay’s applicability for detecting cancers and precancerous lesions.

To learn more about TypeSeq’s availability to external users, please visit the Technical Service Agreement page on the Frederick National Laboratory website.

By Samuel Lopez, staff writer

Image: A Janus G3 Automated Workstation at the Cancer Genomics Research Laboratory, one of the instruments used to conduct the TypeSeq assay, courtesy of the Cancer Genomics Research Laboratory

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