Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor ubiquitously associated with the Epstein-Barr virus(EBV),which is highly prevalent in South China,Southeast Asia,and North Africa.Despite being a highly rad...Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor ubiquitously associated with the Epstein-Barr virus(EBV),which is highly prevalent in South China,Southeast Asia,and North Africa.Despite being a highly radio-sensitive and treatable cancer,a majority of NPC patients are diagnosed in their advanced stage,and locoregional and distant relapses following definitive treatment contribute largely to cancer-specific mortality among these patients.Given that EBV-driven NPC is the predominant variant seen in endemic regions,various EBV detection methods have been developed and are utilized in screening,prognostication,and post-treatment surveillance of NPC patients.While the Immunoglobulin A(IgA)serology assay is the most extensively studied EBV detection method,the detection of plasma EBV DNA released during replication or cellular apoptosis has shown superior outcomes in endemic population screening,prognostication,and detection of distant relapse.Furthermore,there is emerging evidence on the use of circulating tumor cells,microRNAs,DNA hypermethylation,and combination assays in various clinical scenarios.Herein,this paper provides a comprehensive overview of the relevant studies using various EBV detection techniques in the management of NPC.Specifically,the recent advances,clinical evidence,and challenges associated with the clinical application of EBV liquid biopsies in population screening,prognostication,and surveillance of NPC are presented.展开更多
Background:The association of circulating inflammation markers with nasopharyngeal carcinoma(NPC)is still largely unclear.This study aimed to comprehensively explore the relationship between circulating cytokine level...Background:The association of circulating inflammation markers with nasopharyngeal carcinoma(NPC)is still largely unclear.This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China.Methods:The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study(150 NPC patients and 150 controls)using multiplex assay platforms.Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection.Odds ratios(ORs)and 95%confidence intervals(CIs)relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models.The associations were validated in 60 patients with NPC and 120 con-trols in a subsequent nested case-control study within a NPC screening trial.Potential interactions between serum cytokines and Epstein-Barr virus(EBV)relating to the risk of NPC were assessed using a likelihood ratio test.Results:The levels of serum macrophage inflammatory protein(MIP)-1αand MIP-1βin the highest categories were associated with a decreased risk of NPC in both the case-control study(MIP-1α:OR=0.49,95%CI=0.26-0.95;MIP-1β:OR=0.47,95%CI=0.22-1.00)and the nested case-control study(MIP-1α:OR=0.13,95%CI=0.03-0.62;MIP-1β:OR=0.20,95%CI=0.04-0.94),compared with those in the lowest categories.Furthermore,individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study(MIP-1α:OR=16.28,95%CI=7.11-37.23;MIP-1β:OR=12.86,95%CI=5.9-28.05)and the nested case-control study(MIP-1α:OR=86.12,95%CI=10.58-701.03;MIP-1β:OR=115.44,95%CI=13.92-957.73).Conclusions:Decreased preclinical MIP-1αand MIP-1βlevels might be associated with a subsequently increased risk of NPC.More mechanistic studies are required to fully understand this finding.展开更多
文摘Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor ubiquitously associated with the Epstein-Barr virus(EBV),which is highly prevalent in South China,Southeast Asia,and North Africa.Despite being a highly radio-sensitive and treatable cancer,a majority of NPC patients are diagnosed in their advanced stage,and locoregional and distant relapses following definitive treatment contribute largely to cancer-specific mortality among these patients.Given that EBV-driven NPC is the predominant variant seen in endemic regions,various EBV detection methods have been developed and are utilized in screening,prognostication,and post-treatment surveillance of NPC patients.While the Immunoglobulin A(IgA)serology assay is the most extensively studied EBV detection method,the detection of plasma EBV DNA released during replication or cellular apoptosis has shown superior outcomes in endemic population screening,prognostication,and detection of distant relapse.Furthermore,there is emerging evidence on the use of circulating tumor cells,microRNAs,DNA hypermethylation,and combination assays in various clinical scenarios.Herein,this paper provides a comprehensive overview of the relevant studies using various EBV detection techniques in the management of NPC.Specifically,the recent advances,clinical evidence,and challenges associated with the clinical application of EBV liquid biopsies in population screening,prognostication,and surveillance of NPC are presented.
基金supported by the National Key R&D Program of China(No.2016YF0902000 and No.2017YF0907100 to S.C.)the National Natural Science Foundation of China(No.81373068 to S.C.,and No.81672872,No.81272340 and No.81472386 to C.Q.)+2 种基金National Key Research and Development Program of China(No.2014BAI09B and No.2016YFC0902001 to S.C.)the Science and Technology Planning Project of Guangdong Province,China(No.2014B020212017,No.2014B050504004 and No.2015B050501005 to C.Q.)the Provincial Natural Science Foundation of Guangdong,China(No.2016A030311011 to C.Q.).
文摘Background:The association of circulating inflammation markers with nasopharyngeal carcinoma(NPC)is still largely unclear.This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China.Methods:The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study(150 NPC patients and 150 controls)using multiplex assay platforms.Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection.Odds ratios(ORs)and 95%confidence intervals(CIs)relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models.The associations were validated in 60 patients with NPC and 120 con-trols in a subsequent nested case-control study within a NPC screening trial.Potential interactions between serum cytokines and Epstein-Barr virus(EBV)relating to the risk of NPC were assessed using a likelihood ratio test.Results:The levels of serum macrophage inflammatory protein(MIP)-1αand MIP-1βin the highest categories were associated with a decreased risk of NPC in both the case-control study(MIP-1α:OR=0.49,95%CI=0.26-0.95;MIP-1β:OR=0.47,95%CI=0.22-1.00)and the nested case-control study(MIP-1α:OR=0.13,95%CI=0.03-0.62;MIP-1β:OR=0.20,95%CI=0.04-0.94),compared with those in the lowest categories.Furthermore,individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study(MIP-1α:OR=16.28,95%CI=7.11-37.23;MIP-1β:OR=12.86,95%CI=5.9-28.05)and the nested case-control study(MIP-1α:OR=86.12,95%CI=10.58-701.03;MIP-1β:OR=115.44,95%CI=13.92-957.73).Conclusions:Decreased preclinical MIP-1αand MIP-1βlevels might be associated with a subsequently increased risk of NPC.More mechanistic studies are required to fully understand this finding.
