The National Institute of Dental and Craniofacial Research has awarded a five-year, $3.78 million grant to a team of UNC Lineberger Comprehensive Cancer Centers researchers to study to whether experimental tumor and blood tests can accurately detect HPV-linked head and neck cancer, predict if the cancer will respond to treatment, and identify which cancer will recur.
In partnership with University of Texas MD Anderson Cancer Center and the Mayo Clinic, the study builds on research that demonstrated tumor and blood tests developed at UNC Lineberger could identify with high accuracy which patients with HPV-positive oropharyngeal cancer – cancer of the base of the tongue, throat or tonsils – would experience a recurrence and identify these recurrences at earlier time points.
UNC Lineberger’s Gaorav Gupta, MD, PhD, assistant professor of radiation oncology, and Bhisham Chera, MD, associate professor of radiation oncology, have published several smaller studies that showed the blood test, which detects fragments of HPV’s genetic material that have been released into the blood by dying cancer cells, could effectively monitor a patient to determine if their cancer had recurred. The advantage of the blood test is that recurrent tumors would be recognized earlier at a time where more effective treatment may be possible.
UNC Lineberger investigators Natalia Isaeva, PhD, assistant professor of Otolaryngology/Head and Neck Surgery, and Wendell Yarbrough, MD, MMHC, chair of the UNC Department of Otolaryngology/Head and Neck Surgery and the Thomas J. Dark Distinguished Professor of Otolaryngology/Head and Neck Surgery, have published an evaluation of The Cancer Genome Atlas patients showing that certain mutations in tumor cells identified patients who were expected to have better long term survival. Though the findings were promising, the researchers said they need to be confirmed on a larger scale.
“These new studies in partnership with MD Anderson and Mayo clinic will determine if the markers discovered at UNC can identify patients for therapeutic de-intensification, detect recurrent disease at earlier time points, and identify cancer before otherwise clinically detectable,” Yarbrough said.
HPV-linked head and neck cancer in the U.S.
The Centers for Disease Control and Prevention estimates approximately 70 percent of oropharyngeal cancer diagnosed in the United States, roughly 13,000 cases, are probably caused by HPV. The incidence of HPV-associated oropharyngeal cancer has rapidly increased over the last two decades, and it is now the most frequently diagnosed HPV-associated cancer in the U.S. There currently are no approved screening tests for oropharyngeal cancer, but there is an approved vaccine for adolescents and adults to prevent these cancers.
Researchers at UNC and Mayo will conduct a prospective trial to assess whether analysis of tumor cells and a blood test is effective in predicting treatment outcomes or for early detection of recurrences.
“Unlike cervical cancer, there is no screening test currently available for HPV-related oropharyngeal cancer,” Gupta said. “However, it is known that oral HPV infection is the most significant risk factor for the development of oropharyngeal cancer. We will investigate whether our blood-based test may be useful to distinguish patients who have oral HPV infection-only — that is, without cancer— versus those who have an early-stage oropharyngeal cancer. If successful, these studies may pave the way for the potential use of this blood-based test to screen for oropharyngeal cancer, particularly in patients with a known history of oral HPV infection.”
Using biomarkers to guide treatment
MD Anderson is conducting the HOUSTON Trial (HPV-related Oropharyngeal and Uncommon cancers Screening Trial Of meN). This trial will use a test developed in Gupta’s lab to screen saliva and blood markers for the early detection of HPV-oropharynx cancer. The study will also investigate whether the new blood marker can help distinguish oral/oropharyngeal infection from early HPV+ oropharyngeal cancer.
“Most patients have excellent cancer control outcomes, but the treatment can cause significant long-term side effects and health issues,” Chera said. “Using biomarkers to guide treatment decisions will hopefully result in giving patients ‘just the right amount’ of treatment, thus maximizing cancer control and minimizing morbidity.”
Chera said the researchers hope the novel biomarkers will provide prognostic and predictive information that could be used to improve risk stratification and personalize treatment, such as selecting between surgery and radiation and deciding whether to intensify or de-intensify.
The study is expected to run through April 2025.