Carcinogenesis of nasopharyngeal carcinoma: an alternate hypothetical mechanism

Abstract

Current proposed mechanisms implicate both early and latent Epstein–Barr virus (EBV) infection in the carcinogenic cascade, whereas epidemiological studies have always associated nasopharyngeal carcinoma (NPC) with early childhood EBV infection and with chronic ear, nose, and sinus conditions. Moreover, most patients with NPC present with IgA antibody titers to EBV capsid antigen (VCA-IgA), which can precede actual tumor presentation by several years. If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis, one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection. It is perhaps possible that EBV resides within the salivary glands, instead of the epithelium, during latency. This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased susceptibility to NPC and immature salivary gland morphogenesis, the latter of which is influenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene (EDAR), EDARV370A. Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain, but in patients with infectious mononucleosis, EBV has been isolated in this anatomical organ. The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus. Adding to the fact that the fossa of Rosen Müller contains a transformative zone active only in the first decade of life, one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.

Surgery for isolated regional failure in nasopharyngeal carcinoma after radiation: Selective or comprehensive neck dissection

“…Nasopharyngeal carcinoma (NPC) is a common malignant tumor in Southern China, with a high incidence reported in Southeast Asia, North Africa, Alaska, and the Mediterranean basin. 1,2 The highest incidence has been reported among the Cantonese population from the province of Guangdong, where rates range from 22.2 to 30.3 per 100 thousand in males, and from 9.8 to 13.1 per 100 thousand in females. 3,4 NPC is highly radiosensitive, and radiotherapy with or without chemotherapy is the mainstay treatment for NPC.…”

Potential factors associated with clinical stage of nasopharyngeal carcinoma at diagnosis: a case–control study

“…SES can serve as an indicator of various underlying health-related factors, and individuals with a higher SES may be diagnosed at an earlier stage than those with a lower SES [ 17 – 19 ]. In addition to SES, symptom knowledge [ 20 ], physical examinations [ 21 , 22 ], and patient interval [ 23 ] were found to independently associate with the stage of NPC at diagnosis, and factors such as salted fish consumption, cigarette smoking, and a family cancer history are known risk factors for NPC [ 24 , 25 ]. The knowledge and biological effects of these risk factors might be associated with the clinical stage of NPC at diagnosis and confound the effects of other factors.…”

The most important questions in cancer research and clinical oncology

“…On the other hand, the incidence trend of adolescent EBV infection in the form of infectious mononucleosis is reversed, and this effect is also reflected by the incidence of multiple sclerosis. Of interest, the male-to-female ratio for multiple sclerosis is the highest in East Asia and gradually decreases as one moves west, which supports the hypothesis that early EBV infection predisposing East Asians to NPC could be related to a sex-linked recessive form of transmission [21]. …”