The Role of Human Chorionic Gonadotropin Beta (hCGβ) in HPV-Positive and HPV-Negative Oropharyngeal Squamous Cell Carcinoma

Background: This study was carried out to observe the upregulation of the free beta-subunit of human chorionic gonadotropin (hCG beta) 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 hCG beta concentrations (S-hCG beta) were determined by an immunofluorometric assay. The expression of hCG beta 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-hCG beta 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-hCG beta 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-hCG beta was associated with poor DSS. Of the clinical characteristics, higher cancer stage and grade were associated with S-hCG beta positivity. No statistically significant correlation with tissue positivity of hCG beta was seen in these analyses. Conclusion: S-hCG beta may be a potential independent factor indicating poor prognosis, notably in HPV-negative OPSCC.