Cancer initiation and metastasis of virus-related head and neck cancers

Abstract

Epstein-Barr virus (EBV) is associated with the carcinogenesis of nasopharyngeal carcinoma (NPC). In contrast, human papillomavirus (HPV) is associated with the carcinogenesis of oropharyngeal carcinoma. However, it is unknown why such two distinguished neoplasms occur in the closed region.

Nasopharyngeal carcinoma is a highly metastatic neoplasm initiated by EBV genes. Among EBV genes, latent membrane protein 1 (LMP1) is a key regulator of metastasis and oncogenesis. Moreover, LMP1 promotes metastasis with one of the factors, hypoxia-related genes, Siah1. In addition, Siah1 expression is a prognostic factor of NPC. Conversely, we also revealed that LMP1 induces cancer stemness that is important for the initiation of cancer.

Several studies showed that the incidence of HPV-related oropharyngeal carcinoma (HPV-OPC) has increased rapidly in developed countries. Recent studies showed that intrinsic immunity, APOBEC3 is a trigger of viral gene integration to the host genome that is closely associated with the initiation of HPV-OPC.

In terms of tissue tropism with EBV and HPV infection, one report showed that HPV positivity is very rare in EBV-related NPC. However, the copy numbers of EBV-DNA in pharyngeal tonsil (nasopharynx) are higher than those in palatine tonsil (oropharynx) in children. These phenomena suggest EBV tissue tropism to the nasopharynx. It is mandatory to investigate viral carcinogenesis and finally plan to develop new targeted therapies.