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Liquid Biopsy May Help Identify HPV-Associated Oropharyngeal Cancer

— But concerns about false negative results linger

Last Updated July 17, 2023
MedpageToday

MONTREAL – Analysis of circulating human papillomavirus (HPV) tumor DNA and tumor DNA fragment (tumor tissue–modified viral ([TTMV])-HPV DNA using a commercially available blood test – a so-called liquid biopsy test -- appears to have high specificity for identifying oropharyngeal squamous cell carcinoma (OPSCC), though sensitivity is concerning, data from a retrospective observational cohort study suggested.

The assay demonstrated 100% specificity for both diagnosis and surveillance patients with HPV-associated OPSCC, but sensitivity was 91.5% in the diagnosis cohort and 88.4% in the surveillance cohort, researchers reported at the annual meeting of the American Head & Neck Society.

"That means that about one in 10 negative results are false negatives," said Rocco Ferrandino, MD, MSCR, of Icahn School of Medicine at Mount Sinai in New York City, in his oral presentation.

"This assay uses a distinct method that identifies and quantifies a tumor-associated or tumor-modified pattern of DNA fragments that greatly increases assay specificity for identifying an HPV-associated malignant tumor," the researchers wrote in an article simultaneously published in .

"However, evaluation of this assay has been limited to small cohort studies and clinical trials," they added. "The aim of this cohort study was to characterize the diagnostic test characteristics of plasma TTMV-HPV DNA testing for the diagnosis and surveillance of HPV-associated oropharyngeal squamous cell carcinoma in a contemporary clinical setting."

Ferrandino said Mount Sinai was one of the first institutions to use the TTMV-HPV DNA assay for diagnosis and surveillance of patients for occurrence and recurrence of oropharyngeal cancers.

"The current system that we have for diagnosis and monitoring of HPV-associated oropharyngeal cancer has limitations," he said. "We frequently rely on fine-needle aspiration or direct laryngoscopy with biopsy in order to diagnose someone."

"Fine-needle aspiration is known to have a sensitivity on the order of 75% when it comes to squamous cell carcinoma, and direct laryngoscopy with biopsy can be problematic when a patient has an unknown primary or small primary," he pointed out. "In addition, those patients need to be booked for an operating room trip which can take time and delay the diagnosis with respect to surveillance. We frequently rely on PET scans which are known to have a very good negative predictive value, but the positive predictive value of that test can be problematic."

"I think it's important to discuss this with a lot of caveats," Ferrandino added. "This is a retrospective study. It is not powered or designed to assess the utility of this test as a screening tool. We had no standardized protocol for surveillance; it was done by at the discretion of the attending physicians. So, it's hard to make any conclusions about the lead time detection."

"Additionally, the majority of these patients do not have pretreatment results," he said. "Therefore, it's possible that a false negative is the result of the test being negative at baseline. And based on the study design, we can't make conclusions about how the integration of this will affect patients' survival."

"But we show here that there's excellent sensitivity and specificity of circulating tumor DNA that may support its use as an adjunctive biomarker for diagnosis and surveillance," Ferrandino said. "A positive test seems to confirm a diagnosis. Further perspective work, in implementing this test is needed in order to figure out how we best integrate this into diagnosis, treatment and monitoring protocols."

, Miriam Lango, MD, of the University of Texas MD Anderson Cancer Center in Houston, agreed that a prospective clinical validation study is needed for wide spread acceptance of the test.

"Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease," she wrote. "Testing is likely to be increasingly used in routine clinical care, as it is commercially available. It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community."

Testing was conducted at Mount Sinai between April 2020 and September 2022. Ferrandino and colleagues reviewed outcomes among 399 patients, with 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 patients had HPV-associated OPSCC while 11 had HPV-negative disease. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (139 of 152 tests), and specificity was 100% (11 of 11 tests).

In the surveillance cohort, 591 tests were conducted in 290 patients. Overall, 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548) in detecting recurrences. Positive predictive value was 100% (38 of 38 tests), and negative predictive value was 99.1% (548 of 553 tests). The median lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 days.

  • author['full_name']

    Ed Susman is a freelance medical writer based in Fort Pierce, Florida, USA.

Disclosures

Ferrandino and Lango disclosed no relationships with industry.

Primary Source

JAMA Otolaryngology - Head & Neck Surgery

Ferrandino R, et al "Performance of liquid biopsy for diagnosis and surveillance of human papillomavirus-associated oropharyngeal cancer" JAMA Otolaryngol Head Neck Surg 2023; DOI: 10.1001/jamaoto.2023.1937.

Secondary Source

JAMA Otolaryngology - Head & Neck Surgery

Lango M, et al "Circulating human papillomavirus tumor DNA -- ready for prime time?" JAMA Otolaryngol Head Neck Surg 2023; DOI: 10.1001/jamaoto.2023.1938.