血浆 EB病毒游离 DNA检测对监测鼻咽癌患者预后的意义

背景与目的:有报道 , 测定血浆中的 EB病毒游离 DNA( EBV-DNA)的拷贝数可作为诊断及监测鼻咽癌患者病情变化的手段之一.本研究旨在评价血浆 EBV-DNA检测在鼻咽癌患者预后监测上的价值, 并进一步与 VCA/IgA、 EA/IgA进行比较.方法:比较鼻咽癌放疗后 30例远处转移患者、 22例局部复发患者、 24例无 瘤生存者血浆中 EBV-DNA、 VCA/IgA、 EA/IgA水平.分别应用荧光定量 PCR方法检测血浆 EBV-DNA水平,免疫酶法检测 VCA/IgA、 EA/IgA;前瞻性观察 20例初诊鼻咽癌患者放疗前、放疗剂量达 40 Gy时及放疗结束时上述指标的变化. 结果:放疗后各组不同预后患者的血浆 EBV-DNA含量的中位数有显著性差异, 远处转移组为 135 100 copies/ml(四分线区域 5 525～ 1 003 750 copies/ml) >局部复发组的 20 500(四分线区域 0～ 58 500 copies/ml) > 无瘤生存组的 0 copy/ml(四分线区域 0～ 0 copy/ml), P均 < 0.05. 远处转移组的血浆 EBV-DNA水平高者较多, 当阳性标准为 1 000 000 copies/ml时,诊断远处转移组的敏感性为 27.3%,而诊断局部复发组的敏感性为 0.0%,特异性均为 100.0%.在初诊患者放疗前、放疗剂量达 40 Gy时及放疗结束时, EBV-DNA水平逐渐降低,平均含量分别为 32 050 copies/ml(四分线区域 3 880～ 317 750 copies/ml)、 0 copy/ml(四分线区域 0～ 14 375 copies/ml)、 0 copy/ml(四分线区域 0～ 2 940 copies/ml), P均 < 0.05, 而 VCA/IgA、 EA/IgA的水平未见明显变化. 结论: 血浆 EBV-DNA检测可用于监测鼻咽癌患者预后,其价值明显优于 VCA/IgA、 EA/IgA.     

鼻咽癌患者发病前后EB病毒VCA/IgA和EA/IgA滴度动态分析

目的 观察鼻咽癌患者发病前后EB病毒VCA/IgA、EA／IgA滴度的变化规律,及其在鼻咽癌筛查中的作用。方法 收集中山市首次鼻咽癌筛查后12年VCA／IgA阳性人群中54例新发鼻咽癌患者发病前后的血清学资料,用免疫酶法检测EB病毒抗体VCA/IgA和EA／IgA。结果 确诊前1～7年VCA／IgA、EA／IgA总体呈上升趋势。发病前7～4年,VCA／IgA平均滴度在1：21．04上下波动,确诊前第3年起VCA／IgA急剧上升,确诊时几何平均滴度接近1：80,EA／IgA高较为缓慢,确诊时几何平均滴度为1：6．49。放疗后两种滴度均呈快速下降趋势,第4年起接近阳性人群的平均滴度。结论 多数鼻咽癌患者在确诊前3年,VCA／IgA滴度持续增高,但EA／IgA滴度增高缓慢;VCA／IgA可以检出早期鼻咽癌,但EA／IgA作用不大;鼻咽癌发展临床前期平均时间为3年。     

ESTABLISHMENT OF HIGH RISK POPULATION AND PRECANCEROUS LESION OF NASOPHARYNGEAL CARCINOMA(NPC)

ＥＳＴＡＢＬＩＳＨＭＥＮＴＯＦＨＩＧＨＲＩＳＫＰＯＰＵＬＡＴＩＯＮＡＮＤＰＲＥＣＡＮＣＥＲＯＵＳＬＥＳＩＯＮＯＦＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣＩＮＯＭＡ（ＮＰＣ）ＨｕａｎｇＴｅｎｇｂｏ１黄腾波ＷａｎｇＨｕｉｍｉｎ２汪慧民ＬｉＪｉｎｇｌｉａｎ３李...     

Prognostic value of serum Epstein–Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein–Barr virus DNA

Epstein–Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA‐IgA) and viral capsid antigen (VCA‐IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA‐IgA and VCA‐IgA in patients with NPC is less clear. We hypothesize that serum EA‐IgA and VCA‐IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non‐metastatic NPC and undetectable pEBV DNA were included. Serum EA‐IgA and VCA‐IgA were determined by ELISA. After analysis, serum EA‐IgA and VCA‐IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA‐IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA‐IgA >1:120 had significantly inferior 5‐year progression‐free survival (80.4% vs 89.6%, P = 0.025), distant metastasis‐free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse‐free survival (88.4% vs 95.6%, P = 0.023; log–rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA‐IgA became insignificant. Further analyses revealed that serum VCA‐IgA was not an independent prognostic factor in early N (N0–1) or advanced N (N2–3) stage NPC. In summary, although both EA‐IgA and VCA‐IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.     

Comparison of plasma Epstein-Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma

BACKGROUND: Serologic measurement of antibodies to Epstein-Barr virus (EBV) immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was found that plasma EBV DNA concentration is an indicator for the staging and prognosis of patients with NPC. To determine whether there is a correlation between plasma EBV DNA levels and serum levels of IgA/VCA, the authors measured both in patients with NPC and in a control group. METHODS: Real-time polymerase chain reaction was used for quantitative analysis of plasma EBV DNA concentration, and enzyme-linked immunoadsorbent assay was used to measure EBV VCA/IgA in patients with primary NPC (n = 120 patients), locally recurrent NPC (n = 8 patients), and distant metastatic NPC (n = 21 patients) among 76 patients with NPC after the completion of radiotherapy, in 60 patients with NPC in clinical remission, in 38 patients with non-NPC tumors, and in 47 control individuals. RESULTS: The median plasma EBV DNA levels were 6200 copies/mL, 9200 copies/mL, and 2050 copies/mL in patients with primary, locally recurrent, and distant metastatic NPC, respectively, but declined to 0 copies/mL in patients with clinically remissive NPC, in patients who completed radiotherapy, in patients with non-NPC tumors, and in the control group. In contrast, EBV VCA/IgA titers and detection rates remained high in all NPC groups. Plasma EBV DNA levels were significantly higher in patients who had serum VCA/IgA titers > or = 1:640 (median, 83,450 copies/mL) compared with the levels in patients who had titers < or = 1:320 (median, 17,200 copies/mL). Patients with NPC who had advanced TNM stage (Stages III and IV; median, 8530 copies/mL) and T classification (T3 and T4 tumors; median, 8530 copies/mL) had significantly higher plasma EBV DNA levels compared with patients who had early TNM stage (Stages I and II; median, 930 copies/mL) and T classification (T1 and T2 tumors; median, 3700 copies). Patients who had advanced TNM stage NPC had significantly higher mean VCA/IgA titers (1:424) compared with patients who had early TNM stage NPC (1:246), but there was no correlation between IgA/VCA titer and T or N classification of NPC. CONCLUSIONS: The results suggest that plasma EBV DNA detection is a more sensitive and specific marker than the serum IgA/VCA titer for the diagnosis and monitoring of patients with NPC. These findings provide convincing evidence for the use of plasma EBV DNA measurements for the early diagnosis and staging of NPC as well as for monitoring recurrence and metastasis of this tumor.     

Significance of Plasma IgA and IgG Antibodies to Epstein-Barr Virus Early and Viral Capsid Antigens in Thai Nasopharyngeal Carcinoma

Epstein-Barr virus (EBV) is an important causal factor of human nasopharyngeal carcinoma (NPC). High levels ‍of serum IgA and IgG antibodies to EBV early and viral capsid antigens (IgA/EA, IgA/VCA, IgG/EA and IgG/VCA) ‍have been reported in NPC patients. Since specific serum IgA/EA, IgA/VCA and IgG/EA are claimed to be useful ‍serological markers for NPC. In order to evaluate whether plasma IgA/EA, IgA/VCA, IgG/EA and IgG/VCA antibody ‍levels are useful markers for diagnosis and prognosis of Thai NPC, we examined the prevalence of these antibodies ‍in 79 NPC patients, and 127 age-matched controls (47 healthy subjects (HS), 32 cases of other disease (OD) and 48 ‍cases of other cancer (OC)) by using an indirect immunofluorescence assay. The prevalence of plasma IgA/EA, IgA/ ‍VCA, and IgG/EA in NPC patients (55.7, 68.4 and 68.4%) was significantly higher than in the HS (0.0, 0.0 and ‍20.5%,), OD (0.0, 0.0 and 3.1%) and OC (0.0, 0.0 and 20.8%) groups (p<0.05). The prevalence of plasma IgG/VCA ‍in NPC patients (93.7%) was significantly different from those for the OD and OC groups (71.9 and 43.8%) but not ‍for the HS group (89.4%). In NPC patients, the geometric mean titers (GMT) of plasma IgA/EA, IgA/VCA and IgG/ ‍EA were increased with an advanced clinical stage of disease but not IgG/VCA. In contrast, GMT of IgG/VCA was ‍increased with aggressive type of disease (histological type) but not IgA/EA, IgA/VCA, and IgG/VCA. The results of ‍our study suggest that plasma IgA/EA, IgA/VCA and IgG/EA antibodies may be useful markers for diagnosis and ‍assessing prognosis of Thai NPC. ‍     

A comparison of EBV serology and serum cell-free DNA as screening tools for nasopharyngeal cancer: Results of the Singapore NPC screening cohort

We aimed to evaluate the effectiveness of nasopharyngeal cancer (NPC) screening by comprehensive clinical follow-up and adjunctive Epstein–Barr virus (EBV) testing. In a prospective cohort study, 524 individuals with a first-degree family history of NPC were recruited at a university clinical center in Singapore. The cohort was evaluated at baseline and at 6 monthly intervals, with a complete head and neck examination including nasopharyngeal endoscopy. Blood was taken at baseline and at yearly intervals for EBV Viral Capsid Antigen (VCA) IgA, EBV Early Antigen (EA) IgA serology and serum cell-free EBV DNA. Nasopharyngeal biopsy was performed when any irregularity in the nasopharynx was observed, or when EBV markers were elevated. The mean duration of follow-up was 57.7 months, with an average of 8.6 clinical visits per participant. Five participants (0.96%) were identified to have NPC, giving a prevalence of 199 per 100,000 person-years of screening. Four of the five NPC cases identified had asymptomatic T1 disease, at an earlier stage compared to NPC patients diagnosed in the clinic during the same time period (p = 0.0297). All NPC cases identified had elevated EBV-EA IgA titers ≥1:10, with a specificity of 94.6% and a positive predictive value of 15.2%, outperforming EBV-VCA IgA and serum EBV DNA. Two NPC cases were biopsied only because of elevated EBV serology titers, with increasing EBV-EA IgA titers preceding the diagnosis of NPC. In conclusion, screening for NPC is effective in identifying early-stage disease. Adjunctive EBV-EA IgA testing improved the effectiveness of screening.     

Presence of EBV-DNA sequences in nasopharyngeal cells of individuals without IgA-VCA antibodies

Exfoliated nasopharyngeal (NP) cells from 62 normal Cantonese Chinese having IgA/VCA antibodies for more than a year and from 39 similar persons without IgA/VCA antibodies, were tested for the presence of EBV/DNA sequences by spot followed by blot hybridization tests, using the cloned internal repeat of B95-8 viral DNA as probe. Thirteen out of 62 specimens from IgA/VCA-positive (21%) and six out of 39 specimens (15.4%) from IgA/VCA-negative individuals were found to contain EBV/DNA sequences. Forty-six cases (20 IgA/VCA-positive and 26 IgA/VCA-negative) were followed a year later for EBV/DNA sequences and EBV serology. Half of the individuals having EBV/DNA sequences in their exfoliated NP cells in 1981 did not have detectable EBV sequences a year later, and to out of 15 negative individuals became EBV/DNA-positive. There was no obvious correlation between EBV/DNA detectability and EBV serology. (We conclude that the best marker for NPC risk remains the increasing IgA/VCA and/or EA antibody titers.     

Diagnostic Significance of Combined Detection of Epstein-Barr Virus Antibodies,VCA/IgA,EA/IgA,Rta/IgG and EBNA1/IgA for Nasopharyngeal Carcinoma

The objective of this study was to investigate the diagnostic significance of EBV antibody combined detectionfor nasopharyngeal carcinoma (NPC) in a high incidence region of southern China. Two hundred and elevenuntreated NPC patients, 203 non-NPC ENT patients, and 210 healthy controls were recruited for the study. Thetiters of VCA/IgA and EA/IgA were assessed by immunoenzyme assay, and the levels of Rta/IgG and EBNA1/IgAwere determined by enzyme-linked immunosorbent assay. The levels of VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA demonstrated no association with gender or age (p>0.05). The receiver operating characteristic curve andthe area under the curve were used to evaluate the diagnostic value. The sensitivity of VCA/IgA (98.1%) andthe specificity of EA/IgA (98.5%) were the highest. When a logistic regression model was used to combine theresults from multiple antibodies to increase the accuracy, the combination of VCA/IgA+Rta/IgG, whose areaunder the curve was 0.99, had the highest diagnostic efficiency, and its sensitivity, specificity and Youden indexwere 94.8%, 98.0% and 0.93 respectively. The data suggest that the combination of VCA/IgA+Rta/IgG may bemost suitable for NPC serodiagnosis.     

EBV 抗体和EBV-DNA 在鼻咽癌诊断及分期的研究*

目的：评估EBNA1/IgA 、Zta/IgA 、VCA/IgA 和EBV-DNA对不同分期鼻咽癌的诊断效能,探讨各指标阳性率与鼻咽癌分期的关系。方法：收集2010年3 月至2015年9 月中山大学附属中山医院收治的初诊鼻咽癌患者152 例,健康体检者675 例。采用酶联免疫吸附法（ELISA）检测血清EBNA1/IgA 、Zta/IgA 和VCA/IgA 抗体ROD 值,荧光定量PCR （fluorescence quantitative PCR,FQ-PCR ）检测血浆EBV-DNA水平。比较单独和联合应用EBV 标记物对各期鼻咽癌的诊断效能,同时分析各指标阳性率与鼻咽癌分期的关系。结果：鼻咽癌患者EBNA1/IgA 、Zta/IgA 、VCA/IgA 和EBV-DNA阳性率显著高于健康体检者（P < 0.01）。 EBNA1/IgA 在早期鼻咽癌表达相对较高,灵敏度为77.8% ,而EBV-DNA在晚期鼻咽癌的灵敏度最高为88.8% ,两者特异度均在96% 以上。联合检测中EBNA1/IgA 并联EBV-DNA检测的灵敏度为92.1%（早期为82.5% 、晚期为98.9%）,特异度为96.9% 。EBV-DNA阳性率与鼻咽癌临床分期和N 分期呈正相关,Zta/IgA 阳性率与N 分期呈正相关（P < 0.01）。 结论：在无症状人群中进行鼻咽癌筛查,单项指标首选EBNA1/IgA 。晚期患者的辅助诊断则推荐EBV-DNA。两者并联检测可进一步提高鼻咽癌诊断效能。EBV-DNA是鼻咽癌分期和病情监测的重要指标,Zta/IgA 可间接反映淋巴结转移情况,有望对患者病情评估起到参考作用。     

Subtype distribution and long-term titer fluctuation patterns of serum anti-Epstein-Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China：a cohort study

Background: Serum immunoglobulin A antibodies against Epstein–Barr virus (EBV), viral capsid antigen (VCA?IgA) and early antigen (EA?IgA), are used to screen for nasopharyngeal carcinoma (NPC) in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non?NPC participants. Methods: The distribution of baseline VCA?IgA was analyzed between sexes and across 10?year age groups in 18,286 non?NPC participants using Chi square tests. Fluctuations in the VCA?IgA level were assessed in 1056 non?NPC participants with at least two retests in the first 5?year period (1987–1992) after the initial screening using the Kaplan–Meier method. Results: The titers of VCA?IgA increased with age (P < 0.001). Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non?NPC partici?pants with an initial VCA?IgA?positive status and in 20.6% with an initial negative status during the 5?year follow?up. However, seroconversions were common; 85.2% of the participants with a VCA?IgA?positive status at baseline con?verted to negative, and all VCA?IgA?negative participants changed to positive at least once during the 5?year follow?up. The EA?IgA status had a high seroconversion probability (100%) from positive to negative; however, it had a low probability (19.6%) from negative to positive. Conclusions: Age? and sex?specific cutoff titer values for serum anti?EBV antibodies as well as their specific titer fluc?tuation patterns should be considered when defining high NPC risk criteria for follow?up diagnostics and monitoring.     

Therapeutic targeting of the mitotic spindle checkpoint through nanoparticle-mediated siRNA delivery inhibits tumor growth in vivo

We investigated IgA and IgG levels against EBV viral capsid antigen (VCA) and nuclear antigen-1 (EBNA-1) in serum of 223 women with breast cancer (BC) and 309 controls in Guangzhou, China. VCA IgA levels were significantly associated with an elevated risk of BC, with adjusted ORs (95%CIs) of 1.70 (1.05-2.76) (seropositivity) and 2.21 (1.11-4.40) (unit increases in OD value). This association was stronger among young, lean, and HER2+ women. The EBNA-1 IgA levels in OD value, but not seropositivity, were associated with an increased risk of BC among ER+, PR+, and HER2+ patients. None of the IgG variables was related to BC. These results suggest the EBV association with BC in an endemic area of nasopharyngeal carcinoma.     

EBV specific antibody-based and DNA-based assays in serologic diagnosis of nasopharyngeal carcinoma

We assessed 5 EBV specific assays for their capacity to effect serologic diagnosis of suspected NPC. The assays were the immunofluorescent assays, VCA IgA and EA IgA, the enzyme-linked immunosorbent assays specific for EBNA 1 IgA or zta IgG and an EBV DNA assay. Serum samples were taken from 218 symptomatic NPC patients presenting consecutively at a public hospital in Hong Kong, 51 of whom were subsequently diagnosed as having NPC; 4 had EBV-associated lung cancer with similar serology as NPC. The remaining patients included 23 who had other cancers and 140 who had other diseases. Objectives of serodiagnosis under such clinical settings, therefore, are to both exclude and predict a diagnosis of NPC. None of the assays individually can meet both requirements adequately, however. The difficulty was best overcome by combining EBNA 1 IgA and zta IgG. It was shown that 68.3% of the patients gave a confirmed test results, negative or positive, by both tests. A confirmed negative result was associated with a negative predictive value of 99.1%, providing a clear indication to exclude a diagnosis of NPC; a confirmed positive result was associated with a positive predictive value of 86.8%, providing a clear indication to proceed with diagnostic work-up of NPC. The remaining patients gave equivocal test results, being positive for one or the other test, which were associated with a positive predictive value of 43.3% and 24.2%, respectively.     

EB病毒VCA/IgA、Rta/IgG及EBNA1/IgA抗体水平在鼻咽癌高发区不同人群中的分布

目的 观察分析鼻咽癌高发区中的鼻咽癌患者、非鼻咽癌头颈部相似疾病患者和健康体检人群中EB病毒VCA/IgA、Rta/IgG及EBNA1/IgA的抗体水平分布情况。方法 收集211例未经治疗的鼻咽癌患者、203例头颈部相似症状患者和210例健康体检者的血清,采用免疫酶法检测VCA/IgA,采用酶联免疫吸附法（ELISA）检测Rta/IgG和EBNA1/IgA。应用秩和检验、受试者工作特征(ROC)曲线、多分类logistic回归模型等方法对结果进行分析评价。结果 鼻咽癌组的VCA/IgA、Rta/IgG及EBNA1/IgA抗体水平均显著高于头颈部相似疾病组和健康对照组(P<0.001)。头颈部相似疾病组的Rta/IgG及VCA/IgA抗体水平也明显高于健康对照组(P<0.001)。以头颈部相似疾病组和健康体检组为分析人群,分别作相关抗体的ROC曲线,VCA/IgA 的ROC曲线下面积为0.565,Rta/IgG抗体的ROC曲线下面积为0.604,具有统计学意义(P<0.05)。综合年龄、性别和3种EB病毒抗体等因素的多分类logistic回归分析显示,鼻咽癌、头颈部相似疾病和健康体检者的预测准确率分别为95.3％、70.9％和55.2％。结论 在鼻咽癌高发区EB病毒VCA/IgA及Rta/IgG抗体水平在头颈部相似疾病人群和健康人群中存在一定差异,在鼻咽癌的人群筛查和临床诊断中可根据具体情况设定不同的抗体阳性临界值。     

A novel and non-invasive approach utilising nasal washings for the detection of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is an epithelial cancer of the nasopharynx which is highly associated with Epstein–Barr virus (EBV). Worldwide, most of the top 20 countries with the highest incidence and mortality rates of NPC are low- and middle-income countries. Many studies had demonstrated that EBV could be detected in the tissue, serum and plasma of NPC patients. In this study, we explored the potential of assays based on non-invasive nasal washings (NW) as a diagnostic and prognostic tool for NPC. A total of 128 patients were evaluated for NW EBV DNA loads and a subset of these samples were also tested for 27 EBV and human miRNAs shortlisted from literature. EBV DNA and seven miRNAs showed area under the receiver operating characteristic curve (AUC) values of more than 0.7, suggestive of their potential utility to detect NPC. Logistic regression analyses suggested that combination of two NW assays that test for EBNA-1 and hsa-miR-21 had the best performance in detecting NPC. The trend of NW EBV DNA load matched with clinical outcome of 71.4% (10 out of 14) NPC patients being followed-up. In summary, the non-invasive NW testing panel may be particularly useful for NPC screening in remote areas where healthcare facilities and otolaryngologists are lacking, and may encourage frequent testing of individuals in the high risk groups who are reluctant to have their blood tested. However, further validation in an independent cohort is required to strengthen the utility of this testing panel as a non-invasive detection tool for NPC.     

Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. METHODS AND MATERIALS: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. RESULTS: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p = 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. CONCLUSION: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.     

四会市筛查人群中鼻咽癌患者长期生存状况分析

通过比较广东省四会地区参加与未参加筛查人群中鼻咽癌（nasopharyngeal carcinoma）患者的长期生存率,评价运用EB病毒血清抗体指标筛查鼻咽癌的远期效果。方法：对鼻咽癌高发区广东省四会市江谷镇、地豆镇30～59岁健康人群共17 786例运用以检测血清抗EB病毒抗体VCA-IgA、EA-IgA为主的筛查方案进行鼻咽癌筛查,全部人群按实际参加情况分为参加筛查组（10 665例）和未参加筛查组（7 121例）,随访至2007年12月,记录鼻咽癌的发生和死亡情况。运用Log-rank检验比较2组人群中检出鼻咽癌患者的长期生存率。结果：参加筛查组和未参加筛查组鼻咽癌患者的10年总生存率分别为38%和18%（χ2=4.408,P=0.036）;早诊率分别为55.1%和31.0%（χ2=4.727,P=0.030）,前者均明显优于后者。结论：本研究提示在中国南方鼻咽癌高发区开展以EB病毒血清抗体检测为主的鼻咽癌筛查能提高检出鼻咽癌患者的长期生存率,其生存率提高的主要原因为筛查提高了检出鼻咽癌患者的早诊率。     

Increased incidence of IgA antibodies to the Epstein-Barr virus-associated viral capsid antigen and early antigens in patients with chronic lymphocytic leukemia

Antibody titers to Epstein-Barr virus (EBV)-associated early antigens (EA) and the viral capsid antigen (VCA) were determined by ELISA on 263 sera obtained from healthy donors, patients with Hodgkin's disease (HD), non-Hodgkin lymphomas (NHL), infectious mononucleosis (IM), Burkitt's lymphoma (BL), and nasopharyngeal carcinoma (NPC). As expected, most lymphoma patients showed markedly elevated anti-VCA IgG and anti-EA IgG antibody titers. Only one patient in the NHL group (n = 56) consisting of patients with lymphomas other than chronic lymphocytic leukemia (CLL) and hairy-cell leukemia (HCL), and 3 patients with HCL (n = 19) had high antibody titers of the IgA class to VCA and EA. Seventeen out of 48 patients (36%) with CLL had high IgA anti-VCA titers and 10 of these sera (21%) also contained IgA anti-EA. The geometric mean titer (GMT) of IgA anti-VCA was 2,510, the GMT of IgA anti-EA was 780. These antibody titers were about 10 times lower than the corresponding GMT of the NPC patients investigated in this study. The elevated IgG and IgA antibody titers to VCA and EA in CLL and HCL patients seem to reflect an immunodeficiency secondary to the malignant disease leading to reactivation of latent EBV infection. The possibility that at least some of these B-cell lymphomas are associated with EBV cannot be excluded.     

Neutralizing EBV-specific IgA in throat washings of nasopharyngeal carcinoma (NPC) patients.

Throat washings from 26 nasopharyngeal carcinoma (NPC) patients from Hong Kong and Tunisia were studied for the presence of transforming EBV. Only six (23%) were found positive which led to the hypothesis of a neutralizing factor in such salivas. The search for EBV-specific antibodies showed that NPC saliva contained neutralizing VCA and EA IgA (54 and 27% respectively) and VCA and EA IgG (73 AND 54% respectively). Both transforming and non-transforming throat washings contained virus particles as visualized by electron microscopy, but in non-transforming salivas (containing IgA and IgG) the particles were found to be clumped. Comparative study of throat washings from patients with Burkitt's lymphoma (BL); infectious mononucleosis (IM), immunodeficiencies, other cancers, and healthy subjects showed that IgA were restricted to NPC cases.     

The reliability of IgA antibody to Epstein-Barr virus (EBV) capsid antigen as a test for the diagnosis of nasopharyngeal carcinoma (NPC)

Since patients with nasopharyngeal carcinoma were first reported to have elevated levels of IgA antibody to Epstein-Barr virus (EBV) in their sera, workers in a number of countries have studied the possibility that this assay could be used in the diagnosis and monitoring of patients with this disease. In the United States, a collaborative project involving seven centers has been established to investigate the potential value of IgA antibody to EBV viral capsid antigen (VCA) as a clinical tool. In this report, we will summarize the results obtained from three studies: a comparison of EBV serology in three laboratories; a retrospective study of 37 nasopharyngeal carcinoma (NPC) patients and controls, and a prospective study of 126 NPC patients and 683 controls, including 149 patients with other malignancies involving the head and neck. The study of testing comparability in three laboratories demonstrated the feasibility of using this assay in a number of laboratories. The retrospective study confirmed the difference in IgA antibody titers between NPC patients and matched controls. The prospective study showed a relationship between IgA antibody titers and histopathology but not disease stage. IgA antibody titers were elevated more frequently in patients with nonkeratinizing or poorly differentiated types of NPC than for the well-differentiated squamous cell carcinomas. While IgA antibodies to EBV VCA appear to be of value in the early detection and diagnosis of NPC, it is possible that additional serologic tests for immunity to EBV, such as IgG antibody to VCA or early antigen (EA), will improve even further the clinical value of EBV serology in the management of NPC.