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 surgery 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: Patients with HNSCCUP after completing diagnostic workup subsequently treated with single-modality surgery.

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 1780 patients, of whom 294 received surgery 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 surgery as a sole treatment had predominantly p16/HPV positive N1 (TNM7) disease without ECS.

Conclusion: Outcomes for HNSCCUP patients undergoing surgery alone range widely in the literature but may be reasonable in a subset of patients with early-stage p16/HPV positive disease. Data is lacking for p16/HPV negative disease where the potential primary site is more varied and primary emergence appears more common.