Advancing precision detection and treatment
Head and neck cancers remain challenging to diagnose, monitor, and treat because traditional tools—physical examination, imaging, and tissue biopsy—can be limited by sensitivity, specificity, and invasiveness.
Liquid biopsy technologies offer a transformative, noninvasive alternative, particularly for HPV-related head and neck squamous cell carcinoma (HPV-related HNSCC), a disease that continues to rise in incidence.
At The Ohio State University Wexner Medical Center, clinicians and scientists in the Department of Otolaryngology – Head and Neck Surgery are leading efforts to develop liquid biomarker and circulating tumor DNA (ctDNA)–based tools to improve detection, guide therapy, and enhance survivorship for patients with HPV-associated cancers.
“HPV-positive head and neck cancers are on the rise. Patients are often younger when diagnosed and respond remarkably well to treatment, producing a growing population of long-term survivors living with treatment-related side effects,” says Catherine Haring, MD, assistant professor. “Our goal is to determine whether liquid biomarkers can personalize treatment and ultimately improve survival and quality of life for these patients.”
The scientific promise of liquid biomarkers
Liquid biopsies provide real-time molecular information from a simple, repeatable blood draw. By capturing tumor-derived DNA shed through apoptosis or necrosis, ctDNA reflects the biology of the entire tumor rather than a single biopsy site.
Compared with PET/CT or tissue biopsy—both subject to false positives, false negatives, or sampling limitations—ctDNA is more sensitive, more specific, and more readily repeatable.
“HPV-positive cancers are uniquely suited for ctDNA detection because viral DNA is present in every tumor,” notes Dr. Haring. “If we detect HPV DNA in the blood, we know there is active cancer.”
Clinical applications under study
The department is actively integrating biomarker-based monitoring into the care of patients treated for HPV-related HNSCC. Following surgery, radiation, or chemoradiation, clinicians track patients for five years—traditionally using exam findings and imaging that may produce ambiguous results.
Liquid biomarker testing offers a more precise method.
“With biomarker technology, we can test a patient’s blood every few months. If HPV DNA becomes detectable, we have strong evidence of recurrence—often earlier than imaging or exam would allow—giving us the opportunity to intervene sooner,” Dr. Haring explains.
ctDNA is currently the most sensitive available tool for detecting recurrence, enabling earlier salvage therapy and potentially higher cure rates.
Investigators are also evaluating ctDNA as a diagnostic adjunct. Fine needle aspiration can be nondiagnostic, prompting additional procedures and delays. ctDNA may provide rapid, noninvasive diagnostic confirmation and may also carry prognostic information regarding tumor aggressiveness.
Personalizing therapy through ctDNA-guided de-intensification
In collaboration with Sujith Baliga, MD, a radiation oncologist specializing in head and neck cancer, Dr. Haring is co-leading a clinical trial that uses early ctDNA response to guide personalized radiation dosing in nonmetastatic HPV-related HNSCC.
Patients undergo ctDNA testing before therapy and again at week four. Radiation doses are then adjusted according to molecular response.
“Our trial, built on years of foundational work, has shown that we can safely lower radiation doses for patients whose ctDNA becomes undetectable early in treatment,” says Dr. Haring. “This approach reduces toxicity and preserves excellent outcomes—true personalized medicine.”
Therapy de-intensification is crucial. While HPV-related HNSCC carries a high cure rate, long-term survivors frequently experience substantial morbidity from standard dosing. ctDNA-guided treatment offers a path to reducing these side effects without compromising disease control.
Future directions
Liquid biopsy and ctDNA analysis represent a rapidly evolving frontier. The OSU team is working to refine ctDNA assays, expand applications to broader populations, and explore non-blood-based biomarkers such as saliva and urine.
A major long-term goal is developing a screening tool capable of detecting HPV-related HNSCC before symptoms or imaging changes appear. Although this is not yet feasible, advances in ultra-sensitive detection techniques continue to move the field in that direction.
“Early results are extremely encouraging,” Dr. Haring says. “While more research is needed, the potential for liquid biopsies to transform head and neck cancer care is tremendous—and The Ohio State University Wexner Medical Center is leading the charge.”
“As Chair of the Department of Otolaryngology – Head and Neck Surgery, I see this work as emblematic of our mission to advance precision cancer care through multidisciplinary collaboration and scientific innovation. Liquid biomarker research has the potential to reshape every stage of HPV-related HNSCC care—from diagnosis to surveillance to personalized treatment selection. It also reflects our commitment to reducing treatment burden for the growing population of survivors. By advancing tools that detect recurrence earlier and tailor therapy more precisely, we are not only improving survival but also protecting quality of life. Our department is proud to be at the forefront of this transformative work,” says Dr. Rocco.