Tumor-Associated Trypsin Inhibitor (TATI) as a Biomarker of Poor Prognosis in Oropharyngeal Squamous Cell Carcinoma Irrespective of HPV Status

Abstract

<p>Simple Summary<br></p><p>Oropharyngeal squamous cell carcinoma (OPSCC) is a form of head and neck cancer in which human papillomavirus (HPV) infection has been shown to play a major role in disease development. The survival rates of HPV-positive patients are favorable compared to HPV-negative patients, but the reason for this phenomenon remains unclear. The management of OPSCC is complex, and development of novel treatment options is urgently required. Various possible factors affecting survival have been explored, including the tumor environment and cancer-related proteases. Our aim was to study a protease inhibitor known as tumor-associated trypsin inhibitor and its correlation with survival and clinical data in OPSCC patients.<br></p><p>Background: We studied the role of tumor-associated trypsin inhibitor (TATI) in serum and in tumor tissues among human papillomavirus (HPV)-positive and HPV-negative OPSCC patients. <br></p><p>Materials and methods: The study cohort included 90 OPSCC patients treated at the Helsinki University Hospital (HUS), Helsinki, Finland, in 2012-2016. TATI serum concentrations (S-TATIs) were determined by an immunofluorometric assay. Immunostaining was used to assess tissue expression. HPV status was determined with a combination of p16 immunohistochemistry and HPV DNA PCR genotyping. The survival endpoints were overall survival (OS) and disease-specific survival (DSS). <br></p><p>Results: A significant correlation was found between S-TATI positivity and poor OS (<em>p</em> < 0.001) and DSS (<em>p</em> = 0.04) in all patients. In HPV-negative cases, S-TATI positivity was linked to poor OS (<em>p</em> = 0.01) and DSS (<em>p</em> = 0.05). In HPV-positive disease, S-TATI positivity correlated with poor DSS (<em>p</em> = 0.01). S-TATI positivity was strongly associated with HPV negativity. TATI serum was negatively linked to a lower cancer stage. TATI expression in peritumoral lymphocytes was associated with favorable OS (<em>p</em> < 0.025) and HPV positivity. TATI expression in tumor and in peritumoral lymphocytes correlated with lower cancer stages. <br></p><p>Conclusion: Our results suggest that S-TATI positivity may be a biomarker of poor prognosis in both HPV-positive and HPV-negative OPSCC.</p>