HPV biomarker test may support adaptive approach to cancer treatment

Ari Rosenberg, an oncologist at the University of Chicago Medicine, has been trying to improve conditions for people being treated for oropharyngeal squamous cell carcinoma (OPSCC). Incidence of these types of head and neck cancers is increasing, with an estimated 50-70% linked to the human papillomavirus (HPV)¹.

“HPV-associated head and neck cancer tends to have a favourable prognosis,” says Rosenberg. That means HPV-positive OPSCC patients often need less chemotherapy and chemoradiation. A biopsy taken at diagnosis can show whether a cancer is associated with HPV, but tracking response to therapy over time would help minimize side effects – which range from neck pain and fatigue to oral damage and disfigurement – by stopping treatment as soon as the cancer is in complete remission.

To make this response-adaptive treatment work, Rosenberg has been searching for a non-invasive biomarker that’s easy to track over time and shows whether treatment works. HPV DNA may be the answer, but only if the slightest trace can be reliably detected.

Sensitive detection of HPV DNA

“We turned to the Plasma-Safe-SeqS assay, which allows us to detect and quantify HPV DNA in plasma,” says Rosenberg.

Plasma-Safe-SeqS, developed by Sysmex Inostics, is an NGS-based technology originally designed to detect rare mutations in circulating tumour DNA². Rosenberg didn’t need to look for mutations. He used the assay with an HPV-SEQ panel that detects low-level viral DNA from HPV 16 or 18 in plasma. These are the two main HPVs associated with OPSCC.

“You can detect between 5 and 100,000 HPV molecules in a sample with great accuracy,” says Fred Jones, senior director of medical affairs at Sysmex. That broad range of detection is important, because patients might start out with high levels of HPV DNA in their blood that become undetectable after therapy.

If blood levels of HPV DNA are a suitable biomarker for head and neck cancer, tracking patients’ recovery could become easier. Rosenberg explored this in a clinical trial, enrolling patients with HPV-positive OPSCC and taking blood samples before and after induction chemotherapy³.

A recently published evaluation⁴ of nine trial participants showed a clear correlation between changes in HPV DNA levels and treatment response. A subsequent analysis of 25 participants, confirming the link, was presented in a conference poster that has not yet been published.

“At baseline before treatment, all patients had detectable and quantifiable HPV DNA,” says Rosenberg. “During induction chemotherapy, the vast majority of patients clear the HPV DNA from their blood.” Since the HPV-SEQ test is so sensitive, dropping below the detectable range means virtually no HPV is left.

Diagnostic possibilities

Rosenberg’s test could have other uses. One of the trial participants’ cancer returned after treatment, and Rosenberg noticed this correlated with an increase in HPV DNA to within the detectable range. “This is an early signal that may have utility in the detection of recurrent disease,” he says.

Jones envisions other uses for the assay. One possible application is to run the test on saliva instead of blood, which could facilitate the early detection of HPV-associated oral cancers. “This could be a future screen, but right now we’re focusing on its use to monitor cancer treatments and show durable responses.”

For now, the focus is on tracking HPV DNA in the blood of OPSCC patients to monitor treatment. There is work ahead, Rosenberg cautions, but if all goes well, this test could inform treatment and help patients avoid harsh therapies they don’t need.