NEW YORK ─ German biotech Abviris has developed a lateral flow blood test it believes has the potential to enable better decisions about screening, monitoring of therapy response, and early detection of recurrence in a number of cancers stemming from the human papillomavirus.
The test, Prevo-Check, uses a fingerstick of blood to detect levels of HPV 16 L1 monoclonal antibodies, called DRH1, whose levels increase when HPV-induced tumor cells grow. Blood dropped onto the test cassette mixes with a reagent, and if a line appears within 15 minutes it indicates the patient has HPV-induced cancer, Abviris said.
Of the more than 200 HPV virus subtypes, HPV16 is responsible for more than 90 percent of HPV-related head and neck tumors and more than 70 percent of cervical cancers, Abviris noted.
The development of non-invasive tests that use blood or saliva to detect malignant tumors of the head and neck are especially important because cancerous tissue can be difficult to access and detect by any other means.
According to Anna Huber, medical affairs director at Abviris, doctors in German clinics are already using Prevo-Check to decide whether to send patients suspected of HPV-induced cancer for imaging or other follow-up treatments.
However, Abviris believes that the utility of its subtype-specific serological assay, which was CE marked in 2014, extends further to its potential use in hospitals and clinics for screening, monitoring of therapy response, and early detection of recurrence in a number of cancers.
The assay's HPV16- L1-specific monoclonal antibody overcomes a "specificity problem encountered by other test systems," Huber said. "The data show a low number of positive test results among the general population, meaning that it does not pick up transient, subclinical HPV infection, which most people acquire at some point in their lives. [Instead, the test detects] only HPV-induced cancer and pre-cancer, which affects a few of those infected with HPV."
According to Markus Hoffmann at the University of Kiel in Germany, the HPV 16 L1 antibody "apparently reacts to the presence of living tumor cells with a corresponding decrease or increase, offering for the first time the chance to monitor patients with HPV carcinomas post-therapeutically.
"Especially in the head and neck region, the correct identification of HPV-driven tumors is of elementary importance, as the staging of the tumors depends on this," said Hoffmann, who is deputy medical director of the department of otorhinolaryngology, head, and neck surgery at the university and who is not affiliated with Abviris.
With further validation, the Abviris test may prove helpful for clinicians in hospitals and clinics looking to differentiate patients with HPV infections from those with HPV-induced malignancies, said Thomas Weiland, a physician at the Medical University of Graz in Austria, who is participating in studies to validate Prevo-Check's clinical utility.
Prevo-Check demonstrated a sensitivity level of greater than 90 percent and specificity level of 99.3 percent in the detection of anal, head, and neck cancers during a study published recently in EBioMedicine, in which Weiland participated along with research colleagues at medical centers in Austria and Germany.
For patients with tumors induced by HPV-16, the investigators saw a drop in antibody levels following therapy, independent of whether the treatment was surgery or chemotherapy, Weiland said.
They observed a stable low antibody level during follow-up and detected cancer recurrence in two patients before the tumors were revealed by imaging.
The study, in six European medical centers, involved the testing of 1,500 blood samples, including blood from healthy people and patients with head, neck, oral cavity, and anal carcinomas.
Overall, the study points to the potential for using the assay routinely during patient follow-up after therapy, but a broader patient cohort and "longer follow-up is needed to validate that," Weiland said.Â
In the EBioMedicine study, the lateral flow test operated with an off-the-shelf optical reader that allowed for the detection of antibody levels by measuring the optical intensity of a line produced in response to the presence of HPV-specific antibodies. Most doctors are using the test without a reader in clinics throughout Germany, Huber said.
Abviris plans to enable broader adoption and increased reimbursement for Prevo-Check by conducting additional studies and publishing results. Though the firm had collected performance data in the past, the EBioMedicine study represents its first published study in a peer-reviewed journal.
Private insurers in Germany are already providing reimbursement for the test, but further studies are needed to enable international expansion and reimbursement in countries outside Germany, Huber noted.
In the long term, the company plans to launch Prevo-Check internationally, including in the US, which would require obtaining US Food and Drug Administration clearance. Â
To target customers in Germany, the company leverages a direct sales and marketing team, but for future sales outside Germany it intends to ink distribution and out-licensing agreements.
Currently, the firm is planning a large multicenter study in Germany that aims to confirm the results of the EBioMedicine study in a cohort of oropharyngeal cancer patients. In parallel, studies are underway at various German university hospitals to evaluate the biomarker test in its detection of HPV-induced cancers other than for the head and neck, such as penile, anal, and cervical cancers, Huber said.
The study's findings are significant from the perspective of a head and neck oncologist, but they are also "transferable to other HPV-associated malignancies outside the head and neck region," Hoffmann said.
The serological assay is a new tool in a growing repertoire available to physicians seeking to detect and monitor HPV16-driven cancers.
Seeing a need for non-invasive detection of HPV-driven cancers, a number of research teams and companies are developing or supplying tests.
For example, researchers at the University of Queensland, Royal Brisbane and Women's Hospital, and Queensland University of Technology in Australia are developing a DNA-based saliva test that they believe could one day become a screening tool to detect hidden oropharyngeal cancers in patients that are asymptomatic.
Additionally, investigators at the University of North Carolina at Chapel Hill have reached a new milestone for their virus-associated oropharyngeal cancer detection assay, publishing validation data for the test, while a startup has begun to provide the test to early adopters.
The commercial market for HPV and cervical cancer tests is also mature with several diagnostic companies offering products, including Qiagen, which recently announced that it has entered a collaboration with BioNTech to develop and commercialize a tissue-based companion diagnostic to identify patients with squamous cell head and neck cancer caused by specific HPV infections.
For cervical cancer screening, Hologic markets its Aptima HPV Assay, the first US FDA-approved mRNA-based HPV test.