Performance of 18F-FDG-PET/CT as a next step in the search of occult primary tumors for patients with head and neck squamous cell carcinoma of unknown primary: a systematic review and meta-analysis

Purpose We performed a systemic review and meta-analysis to evaluate the performance of F-18-FDG-PET/CT as a next step in the search of occult primary tumors for patients with head and neck squamous cell carcinoma of unknown primary (HNSCC-UP). Methods PubMed and Embase databases were searched from the earliest available date of indexing through February 2021. Eligible studies were those using F-18-FDG-PET/CT to detect occult primary tumors for HNSCC-UP, of which the defining diagnostic workup had been limited to endoscopy with or without CT/MRI. The detection rates were meta-analytically pooled using a random-effects model. Subgroup analyses and meta-regression were performed to explore the source of heterogeneity. A pooled analysis evaluating the false-positive proportions was also performed. Results Sixteen studies with 724 patients were included in this meta-analysis. The pooled detection rate was 40% (95% CI 31-49%), with high heterogeneity (I-2 = 85.2%). No sources of heterogeneity were identified by analyzing multiple subgroups stratified by study design, sample size, ethnicity, use of contrast agent, defining diagnostic workup, image analysis, and reference standard (All P > 0.05). The most common sites of both true-positive cases and false-positive cases were tonsil and tongue base. The pooled false-positive proportion was 9% (95% CI 5-13%). Conclusions F-18-FDG PET/CT is useful as a next step in the search of occult primary tumors in HNSCC-UP patients defined by endoscopy with or without CT/MRI. However, in light of the high false-positive proportion, confirmatory histological investigations should be viewed as necessary practice upon positive PET/CT findings.