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Can ctDNA Accurately Diagnose HPV+ Oropharyngeal Carcinoma?

Most of the currently available circulating tumor DNA (ctDNA) technologies provide a high level of diagnostic accuracy for detecting human papillomavirus (HPV)-associated oropharyngeal squamous cell cancer, according to the results of a systematic review.
The study was presented at the American Academy of Otolaryngology-Head and Neck Surgery 2024 Annual Meeting.
“These findings support the clinical utility of ctDNA in the diagnosis, treatment monitoring, and surveillance of HPV-associated [oropharyngeal squamous cell cancer] and may facilitate earlier disease detection,” Susmita Chennareddy, a medical student at the Icahn School of Medicine at Mount Sinai, New York City, and colleagues wrote in their abstract.
“Liquid biopsy has the potential of revolutionizing head and neck cancer care,” said Cherie-Ann Nathan, MD, Jack Pou Endowed Professor and Chair, Department of Otolaryngology/ Head and Neck Surgery at Louisiana State University, Shreveport, in an interview.
“It provides a less invasive alternative to the traditional tissue biopsy techniques currently used and can give us insight into the genetic underpinnings of HPV-associated oropharyngeal squamous cell carcinoma,” said Nathan, who was not involved in the current study.
To examine the current role of ctDNA in the diagnosis, treatment monitoring, and surveillance of HPV-associated oropharyngeal squamous cell cancer, the researchers searched Medline (Ovid), Embase (Ovid), and Scopus for original articles studying liquid biopsy or ctDNA in this patient population.
Out of 440 studies, they identified 23 for inclusion in the review — 10 retrospective and 13 prospective studies involving ctDNA in the diagnosis or surveillance of oropharyngeal squamous cell cancer.
A total of 13 diagnostic tests used plasma-based droplet digital polymerase chain reaction; four used quantitative PCR; three used digital PCR; and three used next-generation sequencing technology. Of the included studies, one reported accuracy for pre-diagnosis, 18 were for pretreatment, seven were for post-treatment, and 11 were for surveillance/recurrence.
Overall, test sensitivities ranged from 20.6%-100% for pretreatment and from 72%-100% during surveillance. Test specificities were even stronger, ranging from 95%-100% and 87.2%-100% for pretreatment and surveillance, respectively.
The findings were limited by the retrospective design and variations among studies.
Further Study, Clinical Guidelines Needed
“The concentration of circulating tumor HPV DNA in patient bodily fluid samples has been found to correlate with tumor burden, disease progression, tumor metastasis, patient response to treatment, presence of residual disease, disease recurrence, and patient survival,” Nathan told Medscape Medical News. “Additionally, DNA methylation patterns can inform diagnosis,” she said.
Nathan was not surprised by the overall findings of the current study that different liquid biopsy diagnostic assays varied in their ability to detect disease in the pre-treatment and surveillance phases of the patients’ disease and treatment courses.
“These results emphasize the need for further investigations before liquid biopsy can be reliably implemented into clinical care,” she said.
In addition, “lack of a consensus on clinical guidelines and the clinical relevance of certain biomarkers has limited widespread clinical adoption and implementation,” she added.
Looking ahead, studies are needed to establish guidelines for the use of liquid biopsy for patients with HPV-associated head and neck squamous cell carcinoma, to increase access to and affordability of liquid biopsy assays, to ensure that technologies meet adequate clinical standards, and to determine the relevance of various biomarkers at different points in the patient’s disease and treatment course, she said.
As the knowledge of how best to integrate liquid biopsy use into current care paradigms improves, clinicians may be able to gather vital information on patients’ disease status at various stages of care, said Nathan.
“Ultimately, this will allow us to personalize and individualize our approaches to the screening, diagnosis, treatment, and monitoring of head and neck cancer patients,” she said.
The study received no outside funding. The researchers had no financial conflicts to disclose. Nathan had no financial conflicts to disclose.
 
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