Head and neck squamous cell carcinoma of unknown primary - Who can be offered surgery as the sole treatment modality? A systematic review

Objective: Evaluate the role of neck dissection (ND) as the sole treatment modality for patients with cervical head and neck squamous cell carcinoma of unknown primary (HNSCCUP). Design: Systematic review of observational cohort studies with qualitative synthesis. Setting: PubMed, Ovid EMBASE, and Cochrane Controlled register of Trials (CENTRAL) were screened from January 2000 up to October 2021. Participants HNSCCUP patients undergoing ND. Main Outcome Measures The primary outcome was 3-year overall survival (OS). Secondary outcomes included disease-free survival (DFS), primary emergence, regional recurrence, and distant metastasis. Results: Fourteen eligible studies were identified, including 1,780 patients, of whom 294 received ND as their sole treatment (seven studies) with 3-year OS ranging from 43.9% to 100%. 3-year DFS was reported in four studies (n=62) ranging from 42.8% to 67.0%. 5-year OS and DFS were available in three studies (n=31), ranging from 36.6% to 75.0%, and 43.6% to 67.0%, respectively. The rate of primary emergence ranged from 11.1% to 33.3% (seven studies, n=157), regional relapse from 0.0% to 50.0% (five studies, n=60), and distant metastasis from 0.0% to 3.3% (three studies, n=45). Patients undergoing ND as a sole treatment had predominantly p16 positive N1 (TNM7) disease without ECS. Conclusion: Outcomes for HNSCCUP patients undergoing ND alone range widely in the literature but appear reasonable in a subset of patients with early stage p16 positive disease. Data is lacking for p16 negative disease where the potential primary site is more varied and primary emergence appears more common.