Comparative immunohistochemistry characterization of subgroups of dendritic cells and viral oncogenesis in oral and oropharyngeal squamous cell carcinomas

Author(s)

Heitor Albergoni Silveira

• Document type: Master's Dissertation
• Press: Araraquara. 2020-03-19.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araraquara
• Defense date: 2020-02-19
• Advisor: Jorge Esquiche León

Abstract

Head and neck squamous cell carcinoma (SCC) (HNSCC) is the fifth most common type of cancer and the sixth leading cause of cancer death. Recent studies emphasize oral SCC (OSCC) as an entity distinct from oropharyngeal SCC (OPSCC), with the latter having a better prognosis and closely associated with human papillomavirus (HPV) infection. The etiology of HNSCC is multifactorial; however, OSCC is related to tobacco and alcohol abuse, while OPSCC is often associated with HPV infection. Dendritic cells (DCs) are important cells that regulate immune responses, including those linked to tumorigenesis, establishing a connection between the innate and adaptive immune systems. They are divided into two groups: myeloid DCs (myCD) and plasmacytoid DCs (pDC), including immature DCs (imDC) and mature CDs (mDC). The aim of our study was to comparatively analyze, through the immunohistochemistry (HIS) and in situ hybridization (ISH) technique, the infiltration of myCD and pDC, including subgroups of imDC and mDC, in the OSCC (n= 109) and OPSCC (n= 126), as well as analyzing viral oncogenesis (wide-spectrum HPV, high-risk (HRHPV) and low-risk (LRHPV) oncogenic and Epstein-Barr virus [EBV]) by ISH OPSCC (25%) compared to OSCC (11%) showed a significant association with HPV. In OPSCC and OSCC, 19 and 7 shows positivity for HRHPV (only), 6 and 3 LRHPV (only) and 3 and 2 HRHPV/LRHPV (co-infection), respectively. HPV-positive tumors compared to HPV-negative tumors showed a significantly higher proliferative index through the cyclin D1 and Ki-67 markers. The OSCC associated with HRHPV and LRHPV had the highest overall survival rate. Overall, markers for imDC were significantly more frequent in OPSCC than in OSCC. In contrast, OSCC and OPSCC had a higher number of subDC markers. Both neoplasms showed similar amounts of activated pCD. The HPV group showed a greater number of CDs in both neoplasms than the HPV-. It is noteworthy that a significantly higher number of CD207+ and CD123+ cells was observed in HPV-associated OPSCC than in HPV-associated OSCC. We concluded that unlike OSCC, our results show a predominance of imDCs, with an activation profile of immune cells, in OPSCC. The HPV status seems to show an association with the infiltration of DCs in both neoplasms, suggesting antiviral immune responses in the OPSCC associated with HPV. Keywords: (AU)

• FAPESP's process: 18/12734-2 - Comparative immunohistochemical characterization of dendritic cell subgroups and viral oncogenesis in oral and oropharyngeal squamous cell carcinoma
• Grantee: Heitor Albergoni da Silveira
• Support Opportunities: Scholarships in Brazil - Master