Prognostic significance of PET/CT false-positive cervical lymph nodes in head and neck cancer

Cervical lymph node metastasis assessment determines treatment strategy and prognosis in head and neck squamous cell carcinoma (HNC). PET/CT is the standard staging modality but suffers from high false-positive (FP) rates with a substantial portion of imaging-suspicious nodes proving pathologically negative. A fundamental knowledge gap persists; whether imaging positivity itself, despite ultimate pathologic negativity, provides prognostic significance sufficient to justify treatment escalation. This study directly answers this critical clinical question by comparing prognostic outcomes between patients with imaging-positive-but-pathology-negative nodes (FP) and those with concordantly imaging-negative nodes (TN), determining whether the additional imaging positivity differential translates into measurable survival or recurrence disparities. A total of 176 newly diagnosed HNC patients from the ACRIN 6685 cohort undergoing PET/CT staging with complete pathologic confirmation were included. Patients were stratified into FP and TN groups. Cox and competing-risk regression analyses compared recurrence-free survival, overall survival, and HNC-specific survival between two cohorts, adjusted for potential prognostic confounders. Among 176 patients, 137 (77.8%) demonstrated FP findings on PET. Imaging positivity provided no prognostic value; FP and TN cohorts showed equivalent overall survival and HNSCC-specific mortality. Quantitative PET nodal burden (number of suspicious lymph node levels) minimal recurrence association (p = 0.013), but binary nodal presence did not. Imaging positivity alone, when pathology is negative, does not predict worse outcomes. This imaging-pathology discordance carries no prognostic penalty, allowing clinicians to base treatment decisions and prognostic counseling on surgical pathology results rather than escalating care based solely on imaging appearance.​.