Carcinogenesis of nasopharyngeal carcinoma:an alternate hypothetical mechanism

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-lgA),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 Muller 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.

The most important questions in cancer research and clinical oncology

Specific research foci:(1) Mouse models of gamma-herpes virus-68(γHV-68) and polyomavirus(Py V) infections during neonatal versus adult life.(2) For human papilloma virus(HPV)-positive oropharyngeal carcinoma(OPC)—(a) Asking the question: Is oral sex a powerful carcinogen?(b) Examining the evidence for the vertical transmission of HPV infection.(c) Examining the relationship between HPV and Epstein–Barr virus(EBV) infections and nasopharyngeal cancer(NPC) in West European, East European, and East Asian countries.(d) Examining the association between HPVpositive OPC and human leukocyte antigen(HLA).(3) For non-smoking East Asian female lung adenocarcinoma—(a) Examining the incidence trends of HPV-positive OPC and female lung adenocarcinoma according to birth cohorts.(b) Examining the association between female lung adenocarcinoma and HPV.(c) Examining the associations of lung adenocarcinoma with immune modulating factors.(4) For triple-negative breast carcinoma(TNBC) in East Asians—(a) Examining the association between TNBC and HPV.(b) Examining the unique epidemiological characteristics of patients with TNBC. A summary "epidemiological" model tying some of these findings together.

Retreatment in locally recurrent nasopharyngeal carcinoma:Current status and perspectives

1 Background Nasopharyngeal carcinoma(NPC)arises from the epithelial cells that cover and line the nasopharynx.While it is considered a rare cancer globally,it is commonly observed in South China and a few other ethnically distinct racial groups.Due to its propensity to spread early through the submucosal tissue and the highly infiltrative nature of this disease,NPC spreads easily through areas of lesser resistance within the pharyngobasilar fascia with a tendency for neural infiltration[1-3].