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BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) lacks an established screening program, and most cases are diagnosed at advanced stages. Multi-cancer early detection (MCED) blood-based assays represent a promising approach, yet real-world clinical experience with MCED-identified HNSCC remains limited. METHODS: We retrospectively reviewed patients referred to our Otolaryngology department with a positive Galleri MCED result indicating HNSCC between January 2020 and March 2026. Physical exam findings, flexible laryngoscopy findings, imaging, and treatment data for each patient was reviewed. RESULTS: Three patients were included in this case report. All three patients were diagnosed with early-stage p16+ oropharyngeal squamous cell carcinoma despite absent symptoms and largely unremarkable physical examinations. All underwent successful resection with no evidence of recurrent disease at early follow-up. CONCLUSIONS: MCED testing can potentially identify early-stage HNSCC in asymptomatic patients. Otolaryngologists should be prepared to systematically evaluate patients referred following a positive MCED result.
Talwar et al. (2026) studied this question.