Background: This study was carried out to observe the upregulation of the free β-subunit of human chorionic gonadotropin (hCGβ) and its prognostic significance in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). Materials and methods: A total of 90 patients with OPSCC treated with curative intent at the Helsinki University Hospital (HUS), Helsinki, Finland, during 2012–2016 were included. Serum samples were collected prospectively, and their hCGβ concentrations (S-hCGβ) were determined by an immunofluorometric assay. The expression of hCGβ in tumor tissues was defined by immunohistochemistry (IHC). HPV determination was performed by combining p16-INK4 IHC and HPV DNA PCR genotyping. Overall survival (OS) and disease-specific survival (DSS) were used as survival endpoints. Results: S-hCGβ positivity correlated with poor OS in the whole patient cohort (p < 0.001) and in patients with HPV-negative OPSCC (p < 0.001). A significant correlation was seen between S-hCGβ and poor DSS in the whole cohort (p < 0.001) and in patients with HPV-negative OPSCC (p = 0.007). In a multivariable analysis, S-hCGβ was associated with poor DSS. Of the clinical characteristics, higher cancer stage and grade were associated with S-hCGβ positivity. No statistically significant correlation with tissue positivity of hCGβ was seen in these analyses. Conclusion: S-hCGβ may be a potential independent factor indicating poor prognosis, notably in HPV-negative OPSCC.
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