T1 Microscopic Oropharyngeal Carcinoma: Revealing the Unknown Primary Through Diagnostic TORS

BACKGROUND: Head and neck squamous cell carcinoma of unknown primary (hnSCCUP) remains a clinical conundrum. Diagnostic transoral robotic surgery (TORS) now routinely identifies occult primary tumors previously undetected by conventional methods. Here we analyze the histopathology of these tumors, demonstrating novel patterns of submucosal spread in predominantly microscopic tumors. PATIENTS/METHODS: Eighty patients with HPV-mediated hnSCCUP who underwent diagnostic TORS from 2013 to 2022, analyzing tumor histopathology and oncologic outcomes. RESULTS: Primary tumors were identified in 66 (83%) patients averaging 6 × 3 mm in diameter. These microscopic primaries produced cervical metastases over 6 times larger, with many exhibiting ribbon-like submucosal spread through lymphoepithelial crypts that evaded conventional detection. Almost all (98%) were T1 tumors; 71% measured < 1 cm. At 38-month follow-up, 96% of patients remained alive without locoregional recurrence. CONCLUSIONS: Diagnostic TORS reveals that most HPV+ hnSCCUP are actually T1-microscopic oropharyngeal carcinomas, which might constitute a distinct clinical entity requiring new tailored treatment approaches.