Epstein-Barr virus (EBV) contributes to about 1.5% of all cases of human cancer worldwide, and viral genes are expressed in the malignant cells. EBV also very efficiently causes the proliferation of infected human B lymphocytes. The functions of the viral proteins and small RNAs that may contribute to EBV-associated cancers are becoming increasingly clear, and a broader understanding of the sequence variation of the virus genome has helped to interpret their roles. The improved understanding of the mechanisms of these cancers means that there are great opportunities for the early diagnosis of treatable stages of EBV-associated cancers and the use of immunotherapy to target EBV-infected cells or overcome immune evasion. There is also scope for preventing disease by immunization and for developing therapeutic agents that target the EBV gene products expressed in the cancers.

Epstein-Barr Virus and Cancer.

The past three decades have borne witness to many advances in the understanding of the molecular biology and treatment of nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)-associated cancer endemic to southern China, southeast Asia and north Africa. In this Review, we provide a comprehensive, interdisciplinary overview of key research findings regarding NPC pathogenesis, treatment, screening and biomarker development. We describe how technological advances have led to the advent of proton therapy and other contemporary radiotherapy approaches, and emphasize the relentless efforts to identify the optimal sequencing of chemotherapy with radiotherapy through decades of clinical trials. Basic research into the pathogenic role of EBV and the genomic, epigenomic and immune landscape of NPC has laid the foundations of translational research. The latter, in turn, has led to the development of new biomarkers and therapeutic targets and of improved approaches for individualizing immunotherapy and targeted therapies for patients with NPC. We provide historical context to illustrate the effect of these advances on treatment outcomes at present. We describe current preclinical and clinical challenges and controversies in the hope of providing insights for future investigation. Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated malignancy endemic to southern China, southeast Asia and north Africa. The authors of this Review present a comprehensive overview of advances from the past three decades on the pathogenic role of EBV, and the genomic, epigenomic and immune landscape of NPC, which have led to the development of new biomarkers, therapeutic targets and improved treatment approaches for patients with NPC.

Nasopharyngeal carcinoma: an evolving paradigm.

Nasopharyngeal carcinoma (NPC) is a rare malignancy worldwide, but it is endemic in a few areas including Southern China, Southeast Asia, North Africa and the Arctic. The underlying mechanisms behind this remarkable geographic distribution remain unclear. Although Epstein-Barr virus (EBV) infection has been suggested as a necessary cause of undifferentiated NPC, EBV itself is not sufficient to cause this malignancy. Other co-factors, such as environmental risk factors, and/or genetic susceptibility, may interact with EBV to play a role in the carcinogenesis of NPC. Survival rates differ significantly between NPC patients in early stages and late stages. Due to the close associations between EBV infection and NPC risk, EBV-related biomarkers have been used for early detection and screening for NPC in a few high-incidence areas. In the present review article the latest updates are discussed.

/pdf/nasopharyngeal-carcinoma-a-review-of-current-updates-55gsde62gy.pdf

Nasopharyngeal carcinoma: A review of current updates

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

Cancer screening in China: The current status, challenges, and suggestions.

A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.

/pdf/two-epstein-barr-virus-related-serologic-antibody-tests-in-1wsddigvwo.pdf

Two Epstein-Barr Virus–Related Serologic Antibody Tests in Nasopharyngeal Carcinoma Screening: Results From the Initial Phase of a Cluster Randomized Controlled Trial in Southern China

OBJECTIVE:To analyze Epstein-Barr Virus(EBV) infective status and the probability of suffering from NPC in first-degree relatives of sporadic NPC patients,so as to evaluate the relationship of variation of EBV antibodies and the probability of suffering from NPC with heredity and gender factors.METHODS:Serum samples of first-degree relatives of sporadic NPC patients(relatives group) and normal population from the same area(control group) were collected.ELISA was used to detect the serum levels of VCA / IgA and EBNA1 / IgA.The positive rate of antibody,the high probability of suffering from NPC(high-risk rate) and the detection rate of NPC in different population were calculated.RESULTS:No significant difference was found in the positive rates of VCA / IgA and EBNA1 / IgA between relatives group and control group(P0.05).But in male population,the positive rates of EBNA1 / IgA 、 the high-risk rate and the detection rate of NPC in relatives group were higher than those in control group(P0.05).The positive rate of VCA / IgA was unrelated to the gender in each group(P0.05).But in each group,the male had higher positive rate of EBNA1 / IgA and the highrisk rate than the female(P0.05).The detection rate of NPC in the male control group was higher than that in the female control group(P0.05).CONCLUSIONS:In first-degree relatives of sporadic NPC patients,the male have higher positive rate of EBNA1 / IgA and NPC risk than the normal male,while there is no significant difference in the above index between female relatives and the normal female.In first-degree relatives of sporadic NPC patients,the male have higher NPC risk than the female.The male first-degree relatives have higher mobidity rate of NPC than normal population,which illustrates again that heredity plays an important role in tumorigenesis of NPC.

Analysis of EB Virus antibodies levels and probability of suffering from nasopharyngeal carinoma in first-degree relatives of nasopharyngeal carinoma patients

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Two Epstein-Barr Virus–Related Serologic Antibody Tests in Nasopharyngeal Carcinoma Screening: Results From the Initial Phase of a Cluster Randomized Controlled Trial in Southern China

Analysis of EB Virus antibodies levels and probability of suffering from nasopharyngeal carinoma in first-degree relatives of nasopharyngeal carinoma patients