Studies Support MRD Testing to Detect Head and Neck Cancer Recurrence

Head and neck squamous cell carcinoma includes human papillomavirus (HPV)-positive and HPV-negative forms, with recurrence rates reaching 60% depending on stage. Post-treatment surveillance remains challenging because conventional methods, including imaging, can have high false-positive rates and low sensitivity. Addressing these surveillance challenges, newly reported findings demonstrate the clinical performance of a molecular residual disease testing approach across both HPV subtypes.

Signatera from Natera was evaluated in three peer-reviewed publications in npj Precision Oncology, JAMA Otolaryngology, and Advances in Radiation Oncology. The test was assessed for molecular residual disease (MRD) detection, recurrence surveillance, and prediction of adjuvant chemotherapy benefit in head and neck squamous cell carcinoma. The publications included prospective testing after curative-intent surgical resection, pretreatment and surveillance evaluation, and retrospective post-definitive treatment surveillance.

Image: Post-treatment surveillance of head and neck squamous cell carcinoma remains challenging because conventional methods, including imaging, can have low sensitivity and high false-positive rates. (Image Credit: Adobe Stock)

In an institutional cohort study published in npj Precision Oncology, patients underwent prospective Signatera testing after curative-intent surgical resection. Postoperative testing before adjuvant therapy predicted chemotherapy benefit in mucosal head and neck squamous cell carcinoma. Among Signatera-positive patients, chemotherapy was associated with a 35% absolute reduction in two-year locoregional recurrence. Signatera-negative patients showed no differences in disease-free survival, locoregional recurrence, or distant metastases according to whether they received adjuvant chemotherapy.

Complementing these findings, a 168-patient study in JAMA Otolaryngology evaluated Signatera before treatment and during surveillance. Pretreatment samples were positive in 92.2% of cases. In the surveillance setting, serial testing demonstrated 95.2% sensitivity and 99.4% negative predictive value, alongside 100% specificity and 100% positive predictive value.

A retrospective analysis published in Advances in Radiation Oncology further examined recurrence detection in 97 patients with stage 1–4 disease. Serial Signatera testing detected recurrence a median of 4.3 months before radiographic progression, with 91.7% sensitivity and 96.4% specificity. Sensitivity reached 100% among HPV-positive patients, and Signatera positivity was the only independent predictor of progression-free survival in multivariate analysis.

“Head and neck cancer is difficult to treat and carries high recurrence rates, underscoring the importance of catching relapse as early as possible. Collectively, these new studies demonstrate Signatera’s ability to detect recurrence well in advance of clinical signs and predict which patients were likely to benefit from adjuvant chemotherapy,” said Michael Krainock, MD, PhD, MBA, Medical Director, Oncology, Natera.

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