Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
IMPORTANCE: Circulating tumor deoxyribose nucleic acid (ctDNA) has revolutionized the diagnosis and surveillance of human papilloma virus (HPV)-associated squamous cell carcinoma. Its role in HPV-negative oral cavity squamous cell carcinoma (OCC) remains under-investigated. A lack of a unifying oncogene in OCC limits development of a reliable biomarker. SignateraTM (Natera) offers an individualized tumor-specific ctDNA test with high sensitivity for minimal residual disease (MRD) during surveillance in multiple solid tumors. Its utility in OCC has rarely been described.
OBJECTIVES: 1) Identify the sensitivity of pre-treatment ctDNA in HPV-negative OCC. 2) Identify associations between pre-treatment ctDNA and disease burden and prognosis in HPV-negative OCC. 3) Determine the accuracy of post-treatment ctDNA in predicting disease recurrence in HPV-negative OCC.
DESIGN: Single institution retrospective cohort study.
SETTING: Tertiary care referral center, multidisciplinary OCC clinic. All patients with SignateraTM ctDNA draws between December 2022 to October 2024.
PARTICIPANTS: All patients with HPV-negative OCC and one or more ctDNA assays through SignateraTM. Included patients were treated in the primary, recurrent, and salvage settings.
OUTCOME(S) AND MEASUREMENT(S): Pre-treatment and post-treatment ctDNA SignateraTM levels were recorded as mean tumor molecules/mL. All tumors were staged clinically and pathologically according to AJCC 8th edition TNM staging for OCC. Associations between pre-treatment ctDNA, tumor stage, and prognosis were assessed using a linear regression model while associations between pre-treatment ctDNA and recurrence were assessed using the cox proportional hazards model.
RESULTS: A total of 72 ctDNA draws on 33 OCC patients were included. 20 (61%) patients with pathology confirmed OCC had a pre-treatment ctDNA, and 17 pre-treatment draws were positive (85% sensitivity). A higher pre-treatment ctDNA level was insignificantly associated with greater T stage (corr coeff:9.3, p= .358), N stage (corr coeff: 5.8, p=.452), and overall AJCC stage (corr coeff: 6.1, p=.569). A higher pre-treatment ctDNA level was not associated with greater risk of recurrence at 1 year (p=.166). 24 (73%) patients had 52 post-treatment ctDNA draws. Seven (29%) patients progressed through treatment and never had a negative post-treatment ctDNA. There were 20 (38%) positive and 32 (62%) negative ctDNA in the surveillance period. Sensitivity and specificity of post treatment ctDNA draws in predicting recurrence/progression were 91% and 97%, respectively. 10 patients undergoing surveillance developed pathology-confirmed recurrence. Of these 10 patients, 4 had positive ctDNA that preceded clinical or radiographic detection of progression on average by about 110 days (range: 15-239). One patient of the 4 had positive pretreatment and negative posttreatment levels and then later developed a positive ctDNA, indicating recurrence.
CONCLUSION: The SignateraTM ctDNA assay is a reliable tool to establish a pre-treatment baseline in OCC patients. In the surveillance setting, this assay has high sensitivity and specificity in predicting progression and recurrence, thus offering an accurate and novel tool for remote, minimally invasive surveillance in OCC. There were no significant associations between pre-treatment ctDNA levels and tumor stage or recurrence, though this may be due to low power from a limited sample size.