Carcinoma-associated Fibroblasts are a Common Finding in the Microenvironment of HPV-positive Oropharyngeal Squamous Cell Carcinoma

The important role of the human papillomavirus (HPV) is widely established in oropharyngeal squamous cell carcinoma (OPSCC). The behavior of a OPSCCs especially induced by HPV might be influenced by the tissue microenvironment and its changes according to the tumor nature. Recognition of the role of the tumor microenvironment on the behavior of neoplastic cells has led to utilization of the microenvironment to use as therapeutic target. Carcinoma-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, show wide-spread expression of alpha-smooth muscle actin (alpha-SMA). We focused on CAFs, its presence in OPSCC and the relationship with HPV for the first time. Expression of alpha-SMA protein in CAFs of the tumor microenvironment of the 44 formalin-fixed paraffin-embedded tissue blocks from the primary tumor of OPSCC evaluated by immunohistochemistry between HPV-positive and HPV-negative tumors separated by nested polymerase chain reaction. In 44 samples 23 HPV-positive cases were detected. Statistically there were significant differences between histopathologic grade, percent and final score of alpha-SMA and HPV expression. Significant difference between HPV expression and inflammation, intensity, and clinical parameters was not identified in the present study. Our results indicate that CAFs are a common finding in the microenvironment of HPV-positive OPSCC and associated with higher histopathologic grade. Therapeutic strategies to use CAF-mediated drugs need to be considered and evaluated more for treatment of HPV-positive OPSCC.