NEW YORK (GenomeWeb) – Qiagen announced this week that it is launching a molecular test that complements its HPV tests and identifies cancer-specific epigenetic changes in cervical cells. The test, QIAsure, follows either a positive high-risk human papillomavirus test or a finding of abnormal cells in cytology from a Pap smear.
By identifying hyper-methylation of host cell genes, the diagnostic test enables a physician to assess whether the HPV infection is progressing toward cancer, providing guidance for treatment of patients. It can be used with clinician-collected or self-collected samples, according to the firm.
"The test is an important advance for women's health," Tadd Lazarus, chief medical officer of Qiagen, told GenomeWeb. "We are excited because this was a missing piece that had not been picked up by another technology. The test identifies patients with advanced transforming cervical intraepithelial neoplasia (CIN) for immediate treatment and allows those with early transforming CIN to undergo intense surveillance."
Cervical cancer, caused by HPV, affects approximately 500,000 women annually and is the third most common malignancy in women after breast and colon cancer. Women can be screened for HPV, making the cancer highly preventable and treatable. When a woman screens positive for the human papillomavirus, or cytology shows abnormal cells, she is at risk of developing cervical cancer.
Currently available triage options, such as HPV genotyping or tissue-based assays, often have limited clinical value, or are subjective and in many cases lead to false positives or missed cervical disease, Qiagen said. Genotyping of HPV16/18 lacks specificity, leading to false positive results, and cytology lacks sensitivity, leading to missed cervical disease, according to Qiagen.
QIAsure testing stratifies cervical cancer risk by detecting and measuring DNA methylation of two specific genes implicated in cervical cancer. It helps assess transforming HPV infections from non-threatening ones by detecting molecular changes in promoter regions of host cell FAM19A4 and mir124-2 genes, which are hyper-methylated in cervical cancers.
In large-scale studies, the DNA markers used in Qiagen's assay have demonstrated reliable additional insights into a patient's individual risk and contributed to decisions on surveillance and treatment, Qiagen said in a statement. The diagnostic test differentiates itself, according to the firm, by offering both high specificity and sensitivity that are absent from competing solutions.
"In clinical trials QIAsure testing was performed on physician-collected cervical specimens from 250 women with high-risk HPV positive results. QIAsure detected 100 percent of carcinomas, either squamous cell carcinoma or adenocarcinoma, in these samples," Lazarus said.
"The rest of the world has moved and is moving to primary screening without co-testing for cytology. This is a completely complementary product to what we are offering because in the scenario of women who are HPV positive, we want to understand the nature of what they have," he added.
The test is being presented to the public for the first time this week at Eurogin 2016, the international conference for the European Research Organization on genital infection and neoplasia, in Salzburg, Austria.
Qiagen's announcement follows declining HPV test revenues in the US for the firm over the past few years, largely due to increased competition. But the firm will first focus on the European market, with a launch of QIAsure planned for later this year.
"Our desire to introduce it first in Europe is to gain experience in terms of getting feedback from laboratorians and clinicians on how to best get this important message across, and we'll take that and fine tune it for other parts of the world," Lazarus said.
The test has been validated on the Rotor-Gene Q MDx system, a PCR platform that is a member of the modular QIAsymphony family.
In a related development this week, MDxHealth announced that it has granted a non-exclusive worldwide license for its patented methylation-specific PCR technology to Qiagen for use in the QIAsure assay. Under the terms of the agreement, MDxHealth will receive a signing fee plus royalties from future test sales utilizing the technology.
In developing QIAsure, Qiagen collaborated with Self-screen, a spinout of VU University Medical Center in Amsterdam.
A team of researchers in the Netherlands, including those from VU University Medical Center, demonstrated a few years ago that a PCR-based assay for 15 high-risk HPV types, called HPV-Risk, had comparable sensitivity and specificity to a previously validated assay. Their study, published in January 2014 in The Journal of Clinical Microbiology, also demonstrated that the assay — commercially available from Self-screen — produced similar results when run on samples collected by a clinician versus those collected by women.
The authors then took a step toward determining whether HPV-Risk could also reliably detect HPV in self-collected samples. They compared clinician-collected samples to those that women collected themselves using either lavage- or brush-based collection devices. The self-collected cervico-vaginal specimens showed high agreement with the clinician-taken cervical scrapings from the same subjects, using the HPV-Risk assay.
For its part, Qiagen has standardized QIAsure and its HPV tests, including the Hybrid Capture 2, for self-collection.
"We've been at the forefront of the ability of women to collect their own samples," Lazarus said. Women feel it's important that this be available based on personal choice, a collective family decision, or a religious belief, he added.
In addition, researchers using the Cepheid GeneXpert HPV test — one of the primary competitors to Qiagen's test — in a study conducted in Papua New Guinea showed that patient-collected samples produce results similar to physician-collected samples.
The study, published in April in the Journal of Clinical Microbiology, adds to a growing body of evidence supporting the use of self-collected specimens for HPV and other infectious disease testing in both the developing and developed world.