Author: Mike Bassett, Staff Writer, MedPage Today
The use of liquid biopsy for the diagnosis of human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) was more accurate, faster, and less expensive than standard tissue-based biopsies, according to a prospective observational study.
The sensitivity and specificity of this circulating tumor HPV DNA-based approach were 98.4% and 98.6%, respectively, with positive and negative predictive values of 98.4% and 98.6%, reported Daniel L. Faden, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues.
The diagnostic accuracy of this non-invasive approach was significantly higher than standard of care (Youden index 0.968 vs 0.707, P<0.0001), they noted in Clinical Cancer Research.
In addition, liquid biopsy reduced the time to diagnosis from a median of 41 days to 15 days, and estimated costs associated with this method were about 36% to 38% less than the traditional biopsy approach.
“Currently the way we diagnose HPV-associated cancer is either with a needle biopsy of a neck lymph node or a tissue biopsy from the oropharynx — and these approaches have a couple of different limitations,” Faden told MedPage Today. Not only are they invasive and painful for patients, but needle biopsy of a neck lymph node has high failure rates due to a lack of adequate cellular material.
“So, patients might have to undergo a repeat biopsy to get the diagnosis we are waiting for,” he noted. “That adds time to diagnosis, and we know that time from presentation to when patients start treatment impacts outcomes, so we want to start that as soon as possible.”
Considering these challenges, Faden and colleagues assessed a circulating tumor HPV DNA-based diagnostic approach compared with standard clinical workup.
They prospectively enrolled 70 patients presenting with a new or suspected diagnosis of HPV-associated oropharyngeal squamous cell carcinoma, nasopharyngeal carcinoma, or sinonasal squamous cell carcinoma, all of whom underwent standard-of-care diagnostic workup, as well as 70 control patients who were subsequently diagnosed with HPV-negative HNSCC.
Blood samples were collected and processed for circulating tumor HPV DNA, and analyzed with custom droplet digital PCR assays for HPV genotypes 16, 18, 33, 35, and 45.
Of the 70 patients in the HPV-positive group, 61 were available for analysis. Fine-needle aspiration was the first diagnostic approach in 37 patients, while primary tissue biopsy was the first for 24 patients. The overall diagnostic success rate on the first attempt was 72%, meaning that 17 patients (28%) had to undergo a repeat biopsy to achieve diagnosis.
Faden and colleagues also evaluated the diagnostic accuracy of liquid biopsy in combination with cross-sectional imaging and physical examination.
“We realized that people may be skeptical about making a diagnosis of cancer just off a blood test, and not having a traditional tissue biopsy,” Faden said. “In order to build confidence in having this non-invasive diagnosis, we took our liquid biopsy and combined it with routine things patients receive when they first present — a physical exam and cross-sectional imaging with either a CT or MRI scan.”
The researchers found that this approach yielded a specificity of 98.6%, but a sensitivity that was slightly lower (95.1%). “But this was because some patients lack classic imaging or physical exam findings, such as a mass you can see in the throat or enlarged lymph nodes in the neck,” he explained.
Faden and colleagues are preparing to open a trial designed to validate the findings from this study next year, and plan to use liquid biopsy to make real-time decisions for patients during treatment to personalize their care.