Disclosures: NCI supported the study. Swiecicki reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
July 14, 2021
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Blood test may detect treatment failure earlier in oropharynx squamous cell cancer subset

Disclosures: NCI supported the study. Swiecicki reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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A novel noninvasive droplet digital polymerase chain reaction-based assay predicted treatment response months before standard imaging scans among a cohort of patients with metastatic HPV-associated oropharynx squamous cell carcinoma.

The study results, published in Oncotarget, elucidate the coming role for predictive circulating biomarkers in metastatic head and neck cancer, in addition to the enormous technical challenge surrounding interpretation of the tests, Paul L. Swiecicki, MD, clinical assistant professor of medical oncology and internal medicine at University of Michigan, told Healio.

Paul L. Swiecicki, MD, clinical assistant professor of medical oncology and internal medicine at University of Michigan

“Comparison of [circulating tumor DNA] studies is exceptionally complicated because [although] two tests may be looking at the same molecule, such as HPV, their testing performance may be markedly different based on the biologic design of the test. As a community, we need to focus on harmonization of these tests, appropriate clinical validation, and proof of therapeutic utility before they enter the clinic,” Swiecicki said.

HPV-associated head and neck cancer is increasing in incidence, yet no biomarker exists that is predictive of recurrence or response to therapy.

“In patients with metastatic disease, treatment is palliative with low response rates, significant toxicities and even mild progression of disease that results in immense patient suffering due to pain, as well as the inability to speak, swallow or even breathe,” Swiecicki said. “Despite this, we can only objectively assess response by radiographic imaging after about 9 weeks of treatment. Our multidisciplinary team sought to identify a noninvasive biomarker to identify patients in which systemic therapy was not efficacious. Our vision was that if we were able to create such a test, we could change therapy for these patients, thereby avoiding undue toxicities and exposure to an inactive therapeutic.”

Investigators developed and validated the droplet digital polymerase chain reaction (PCR)-based assay for HPV 16 circulating tumor DNA (ctDNA) and evaluated plasma HPV 16 ctDNA for predicting treatment response using 102 samples from 16 patients with metastatic HPV-associated oropharynx squamous cell carcinoma. Among them, 12 patients (mean age, 62 years; 75% men) had HPV 16. Six of these patients had ctDNA levels assessed during a total of 18 distinct courses of treatment, with an average of five samples taken per treatment regimen. Seven patients underwent treatment with immunotherapy-based regimens and 11 treatment courses contained cytotoxic chemotherapy.

Researchers used a cut point for prediction of disease progression with optimal sensitivity and specificity of at least a 60% increase in HPV 16 ctDNA. Results showed an area under the curve of 0.84 (P = .02), sensitivity of 88.9% (95% CI, 52-99.7), specificity of 88.9% (95% CI, 52-99.7), positive predictive value of 88.9% (95% CI, 55-98.1) and negative predictive value of 88.9% (95% CI, 56-98.1).

The researchers then assessed whether early changes in HPV 16 ctDNA predicted future radiographic response to therapy by evaluating changes between baseline HPV 16 ctDNA and plasma drawn before treatment cycle two. Results showed a significant association between changes in HPV 16 ctDNA at cycle two and later evidence of disease progression (Wilcoxon P = .02).

Researchers also observed a significant association for changes in HPV 16 ctDNA across RECIST response categories (Kruskal-Wallis P = .04). In addition, they found a strong positive association between percent change observed in plasma draw before treatment cycle two and plasma drawn synchronous to restaging imaging (Pearson rho= 0.9).

“Our new blood test is exceptionally sensitive and precise for the detection of HPV ctDNA, and not only can the test predict clinical benefit after one cycle of systemic therapy in HPV-associated recurrent/metastatic head and neck cancer, but this is the first time that HPV ctDNA has been shown to be potentially predictive of response to systemic therapy,” Swiecicki said. “We also showed that the blood test could distinguish patients exhibiting ‘pseudoprogression’ as a result of immunotherapy vs. those having true progressive disease. If these findings are validated, this noninvasive droplet digital PCR-based assay could change the treatment paradigm for metastatic head and neck cancer.”

Investigators are now validating the test across various clinical settings and refining the assay to perform even better, according to Swiecicki.

“Clinically, we are working with partners to validate the predictive value of this test in metastatic HPV-associated head and neck cancer. If validated, this would serve as the basis for a biomarker-adapted clinical trial. Outside of metastatic disease, we have already shown that the test can predict recurrent disease in patients who have undergone curative surgery more than a year prior to development of symptoms,” Swiecicki said.

Future versions of the assay could be used in screening for HPV-associated head and neck cancer, as well as early detection for recurrence, he added.

“Access to health care and screening tests is a major societal issue and we believe future versions of this assay may allow us to not only better detect HPV-associated head and neck cancer, but allow patients to do so without a blood draw and having to leave home,” Swiecicki said.

For more information:

Paul L. Swiecicki, MD, can be reached at Rogel Cancer Center, 1500 E. Medical Center Drive, Floor B1 Reception E, Ann Arbor, MI 48109; email: pswiecic@med.umich.edu.