Squamous Cell Carcinoma of Unknown Primary Head and Neck

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2 Key Points ➤ Management decisions for squamous cell carcinoma of unknown primary (SCCUP) are best decided in the context of a multidisciplinary tumor board and with careful consideration of human papillomavirus (HPV) status, disease burden and distribution in the neck, a patient's overall health and well-being, potential treatment-related toxicity, and rehabilitation potential for functional recovery. Preoperative Evaluation ➤ 1.1 Patients undergoing evaluation for a neck mass suspicious for squamous cell carcinoma should undergo a thorough history and physical examination including fiberoptic laryngoscopy that may be complemented with advanced visualization techniques such as narrow band imaging (NBI) to facilitate identification of the anatomic location of the primary tumor and to inform potential therapeutic management options. (Moderate recommendation; IC-B-L) ➤ 1.2 Fine-Needle aspiration or core biopsy of a clinically suspicious neck mass should be performed. (Strong recommendation; EB-B-I) ➤ 1.3: High-risk human papillomavirus (HR-HPV) testing should be done routinely on level II and III SCCUP nodes. Epstein-Barr virus (EBV) testing should be considered on HPV-negative metastases. (Moderate recommendation; EB-B-I) Note: HR-HPV testing may be done non-routinely for squamous cell carcinoma metastases at other nodal levels when clinical suspicion is high. ➤ 1.4: Contrast enhanced computed tomography (CECT) of the neck should be the initial test for work-up of metastatic cervical lymphadenopathy. (Strong recommendation; EB-B-I) ➤ 1.5: If a primary is not evident on clinical examination and CECT, positron emission tomography (PET)-CT should be the next diagnostic step. (Strong recommendation; EB-B-I)

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