Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Introduction: Fine needle aspiration (FNA) frequently differentiates etiologies of the adult lateral neck mass including second branchial cleft cysts and lymph node metastases from human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). However, FNA can yield non-diagnostic results, especially in cystic masses with limited cellular material. Non-diagnostic FNA necessitates further workup and may delay diagnosis. HPV circulating tumor DNA (ct-DNA) is a blood-based test that can detect fragments of tumor-modified HPV in plasma of patients with HPV-driven OPSCC. We hypothesize that HPV ct-DNA may be a useful diagnostic tool for patients with lateral neck masses and non-diagnostic FNA, as a positive ct-DNA level should suggest an HPV-positive OPSCC diagnosis. We aim to report operating characteristics of ct-DNA in work-up of the biopsy-indeterminate lateral neck mass.
Methods: We retrospectively identified all adult patients with pre-treatment ct-DNA levels at two tertiary care centers. We then selected patients with non-diagnostic FNA of an enlarged cervical lymph node preceding ct-DNA draw. We excluded patients with conclusive pathologic diagnosis by any means at the time of ct-DNA draw. Patient demographics, neck mass characteristics, biopsy details and ct-DNA levels were summarized with descriptive statistics. The final pathologic diagnosis was characterized as benign or malignant, enabling sensitivity and specificity calculations.
Results: We identified 30 patients with ct-DNA obtained following non-diagnostic FNA of an enlarged cervical lymph node. The average age was 62 years (+/- 12 years) and most patients had a history of smoking tobacco (18, 60%). The median mass size was 3.0cm (range: 1.3 – 8.2cm) and all were located in level 2. A median of 2 biopsies were attempted per mass (range: 1– 4 biopsies). Sixteen patients (53%) had additional biopsies following initial non-diagnostic FNA. When >1 biopsy was performed, there was a median of 24 days between first and last biopsy (range: 3–212 days). Of patients with >1 biopsy, most had FNA re-attempted (12/16, 75%), while 4 patients (25%) had subsequent core-needle biopsy. In the 12 instances where FNA was repeated, results were often persistently indeterminate (9, 75%). Following initial non-diagnostic FNA, ct-DNA was negative in 9 cases (30%) and positive in 21 cases (70%). The median ct-DNA level when positive was 232 (range: 4 – 46,506). HPV-positive OPSCC was ultimately diagnosed in 24 patients (80%) while benign entities were identified for 6 patients (2 fibrosis with lymphoplasmacytic inflammation, 2 nodular fasciitis, 1 xanthogranulomatous change, 1 branchial cleft cyst). Ultimate tissue diagnosis was obtained via: transoral biopsy (17, 57%), excisional lymph node biopsy (7, 23%) or subsequent needle biopsy (6, 20%). In all 6 patients with benign neck masses, pretreatment ct-DNA was negative (specificity: 100%). Of 24 patients with p-16+ SCC, pretreatment ct-DNA was positive in 21 cases and negative in 3 cases (sensitivity: 87.5%).
Conclusions: When FNA of a lateral neck mass is non-diagnostic, a positive ct-DNA level is highly predictive of a malignant etiology and should trigger further investigation. Further consideration should be given to utilizing HPV ct-DNA as part of the diagnostic workup for lateral neck masses following a non-diagnostic FNA.