Etiology

Presently, there is no known causative NPC agent identified. However, there is a consistent association of past Epstein Barr Virus (EBV) infection and the presence of histological type II (Non-Keratinizing Squamous Cell Carcinoma) and type III (Poorly Differentiated Squamous Cell Carcinoma) NPC. Primary tumors isolated from the nasopharynx and metastatic lymph nodes from the neck have many copies of EBV genomes, making this a reliable biological marker of NPC. The mechanism and the role of EBV in the pathogenesis of NPC still remain unknown. Etiology of Type I (keratinizing Squamous Cell Carcinoma) is likely related to smoking and alcohol use.

Genetics

Family History – 2-15 x increased risk over general population
Male to female incident ratio is 3:1
Association with major histocompatibility complex class I

Environmental Contributors

• Salted Fish
• Preserved Vegetables (nitrosamine)
• Reduced fruits/veggies
• Household smoke/fume
• Tobacco/EtoH
• Occupation

EBV

EBVThe Epstein Barr Virus (EBV), also called human herpesvirus 4 (HHV-4), is a virus of the herpes family, and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis (glandular fever). EBV infection normally occurs in early childhood.

The association between EBV infection and NPC is well documented and cells with EBV genome are present in virtually all NPC cells. Epstein-Barr virus (EBV) was classified by the International Agency for Cancer Research (IARC) as a Class I carcinogen for NPC in 1997. Both the WHO and AJCC have classified it as the earliest form of cancer, carcinoma in-situ (Stage 0), with the presence of Epstein Barr Virus (EBV) DNA in the cancer cell.

Although 95% of the adult population worldwide may be infected with EBV at some point in their lives, the genesis of NPC is multifactorial. The presence of EBV is crucial to the formation of NPC but it is not the only cause. Currently, it is known that many factors can result in the activation of EBV, such as environmental carcinogens, genetics and/or immune deficiency.

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