NGS Leveraged for HPV Diagnostic Tool

NGS Leveraged for HPV Diagnostic Tool
Human papilloma virus, computer artwork.

The current methods for diagnosing human papilloma virus are if a person has visible symptoms on their skin, or if a person have an abnormal cervical smear result. This may all change in the future, as researchers with the Margaret Cancer Center report in Clinical Cancer Research that they have developed a test leveraging next-generation sequencing to detect it from a blood sample.

“HPV DNA offers a convenient ctDNA marker for HPV-associated malignancies, but current methods such as digital (d)PCR provide insufficient accuracy for clinical applications in patients with low-disease burden,” the researchers wrote. “We asked whether a next-generation sequencing approach (HPV-seq) could provide quantitative and qualitative assessment of HPV ctDNA in low-disease-burden settings.”

In a cohort of patients with advanced cervical cancer, researchers reported their new sequencing method detected 20-fold lower levels of HPV circulating tumor DNA.

“Increasingly, as clinicians we’re focused on precision medicine and making sure we’re not over-treating people while still curing them, that’s a very difficult balance to strike,” Princess Margaret senior scientist Scott Bratman, Ph.D., explained.

“We conducted preclinical technical validation studies on HPV-seq and applied it retrospectively to a prospective multicenter cohort of locally-advanced cervix cancer patients (NCT02388698) and a cohort of oropharynx cancer patients,” wrote the researchers. “HPV-seq results were compared with dPCR. The primary outcome was progression-free survival (PFS) according to end-of-treatment HPV ctDNA detectability. Results: HPV-seq achieved reproducible detection of HPV DNA at levels <0.6 genome equivalent in cell line data.”

“We’re really at the cusp of a revolution from a technology, clinical implementation, and standard of care standpoint, where five to 10 years from now we will not be treating everybody with the same dose of radiation and chemotherapy, and then waiting months to see if the treatment was effective,” Bratman said. “I’m confident we will be giving much more tailored doses.”

“Patients who need more treatment will then be able to continue on, or different treatments can be added,” he continued. “We can spare the vast majority of patients who will not need those interventions and provide them with a greater quality of life once they’re cured of the cancer.”

The new technique may one day be used to guide treatment for other viruses that cause cancer such as certain types of stomach cancer and lymphomas.

Bratman added that this work was made possible by the collaborative atmosphere at the Princess Margaret Cancer Centre.

“It’s particularly good here in terms of spanning those different domains, multi-disciplinary and translational research, and that was definitely a major factor in getting this study done,” Bratman said.