Head and Neck Cancer of Unknown Primary: A Multicenter Retrospective Cohort study in Northern Thailand, an Endemic Nasopharyngeal Cancer Area

Objective: This study aimed to evaluate the characteristics and oncological outcomes of head and neck carcinoma of unknown primary (HNCUP) patients in an endemic nasopharyngeal cancer (NPC) area.

Methods: One hundred and forty-four HNCUP patients curatively treated between January 1995 and December 2022 from 5 centers were retrospectively recruited onto the study to analyze the clinicopathological characteristics and oncological outcomes and compare them with historical data. A multivariate Cox proportional hazards model analysis was performed to evaluate factors affecting survival outcomes. A propensity-matched pair analysis of the patients with positive and negative EBV-encoded small RNA (EBER) staining was applied to compare the characteristics and outcomes between the two groups.

Results: The median follow-up time was 45 months. Most patients (88.2%) received total mucosal irradiation (TMI). Primary tumor emergence (PTE) was detected in 6 patients (4.2%) who did not have TMI. The 5-year overall survival (OS), disease-free survival, and locoregional recurrence-free survival were 51.3%, 64.9%, and 72.7%, respectively. Extranodal extension and N3 compared with the N1 stage were the significant independent predictors for OS (HR 2.90, 95% CI 1.12-7.51, p = 0.028 and HR 3.66, 95%CI 1.23-11.89, p = 0.031, respectively). The matched-pair analysis demonstrated comparable all survival outcomes between the EBER-positive and -negative groups. All patients in the matched pair analysis received TMI, and no PTE was detected.

Conclusion: Our survival outcomes were comparable to previous studies with a low rate of PTE. The matched pair analysis of EBER-positive and -negative groups revealed similar oncological outcomes and no primary tumor emergence when total mucosal irradiation was administered.