Comparative immunohistochemical characterization of dendritic cell subgroups and viral oncogenesis in oral and oropharyngeal squamous cell carcinoma

Abstract

The head and neck squamous cell carcinoma (HNSCC) is the fifth most common type of cancer and the sixth cause of cancer death. Recent studies emphasize oral SCC (OSCC) as a distinct entity of oropharyngeal SCC (OPSCC), with the latter showing a better prognosis and closely associated with human papillomavirus (HPV) infection. The etiology of HNSCC is multifactorial; however, the OSCC is related to tobacco and alcohol abuse, while OPSCC is often associated with HPV infection. Dendritic cells (DCs) are important cells which regulate immune responses, including those linked to tumorigenesis, establishing a connection between the innate and adaptive immune system. They are divided into two groups: myeloid DCs (myDCs) and plasmocytoid DCs (pDCs), including immature DCs (imDCs) and mature DCs (mDCs) stages. The mDCs are responsible for initiate protective immune mechanisms against foreign agents, including virus, whereas imDCs induce immune tolerance. The objectives of the present study will be to comparatively analyze, for immunohistochemistry (IHC) and in situ hybridization (ISH), the myDCs and pDCs infiltration, including mDC and imDC subgroups, in the intratumoral compartment of OSCC (n=100) and OPSCC (n=50), as well as to analyze viral oncogenesis (HPV and Epstein-Barr virus [EBV]), focusing clinicopathological associations, prognostic and therapeutic factors. Our results aim to contribute to the elucidation of OSCC and OPSCC pathogenesis and to determine if differences in the DC subgroups infiltration, including their activation stages, in correlation with viral oncogenesis, may explain the biological behavior of these tumors. (AU)