488683人鼻咽癌普查基本方案分析

目的分析488 683人鼻咽癌普查结果,其中20 726人是广西梧州市鼻咽癌高发现场1980年普查及10年追踪观察和对查出EB病毒IgA/VCA抗体阳性者20年追踪观察结果,467 957人是现场以外其它地区普查结果,两者结果比较分析提出鲻鼻咽癌普查和社区应用基本方案.方法应用免疫酶法检测EB病毒IgA/VCA抗体,间接鼻咽镜配合,在现场和现场以外其它地区进行鼻咽癌普查.结果现场20 726人普查及10年和20年追踪观察,IgA/VCA抗体阴性19 590人10年内发生鼻咽癌4例,其中3例确诊时IgA/VCA抗体已显阳性反应,仅1例仍为阴性,IgA/VCA抗体阳性1 136人普查及20年追踪观察检出鼻咽癌60例,其中接受随访的54例中,有46例属早期,早诊率85.2%,IgA/VCA抗体诊断鼻咽癌符合率98.3%.现场以外其它地区普查467 957人,检出鼻咽癌188例,其中属于早期患者为164例,早诊率87.2%,可以重复现场结果.结论免疫酶法检测EB病毒IgA/VCA抗体普查鼻咽癌,间接鼻咽镜配合,方法简单、价廉、诊断符合率高,可以检出鼻咽癌早期病人,是鼻咽癌普查或社区服务的首选基本方案,其它抗体检测可在这基础上互补,符合成本效益卫生经济学观点.     

2007～2008年广西苍梧县石桥镇鼻咽癌普查结果初步分析*

目的:通过鼻咽癌普查了解广西苍梧县高发区鼻咽癌流行状况,探讨可持续发展的鼻咽癌早诊早治普查模式。方法:于2007年6 月～2008年12月在广西苍梧县石桥镇鼻咽癌现场进行鼻咽癌普查。在鼻咽癌现场建立人口档案;进行流行病学调查;参加普查者均进行头颈部检查及间接鼻咽镜检查,鼻咽癌EB病毒壳抗原IgA 抗体（IgA/VCA ）和早期抗原IgA 抗体（IgA/EA）血清学检测;检查结果可疑和血清学结果阳性者均进行鼻内镜检查;鼻咽部可疑病变者行活组织病理检查;鼻咽癌普查结果均输入电脑,应用EpiData3.1 建立数据库。结果:鼻咽癌现场筛查人群8 458 人,其中EB病毒IgA/VCA 阳性522 例,EB病毒IgA/EA阳性28例,进行鼻内镜检查410 例,鼻咽部活组织检查45例,检出鼻咽癌12例,其中早期鼻咽癌6 例,接受治疗11例。鼻咽癌人群检出率141.87/10 5,早诊率50% ,治疗率91.6% 。结论:广西苍梧县鼻咽癌早诊早治普查方案是鼻咽癌防治的重要策略之一,而鼻咽癌早诊早治普查工作应持续发展。      

30岁～39岁人群鼻咽癌血清学检测

目的:为了进一步研究EB病毒和鼻咽癌的关系,达到早期发现和早期治疗鼻咽癌的目的,我们在梧州市再次进行了鼻咽癌血清学检查,对象主要是30岁～39岁人群。并将结果和1980年我们对40～59岁人群的鼻咽癌普查结果进行比较。方法:抽取广西梧州市30～39岁正常人群的静脉血2ml,分离血清,于-20℃保存备用;用免疫酶法检测血清中VCA—IgA和EA-IgA;对VCA-IgA抗体阳性者进行临床检查,可疑者作活检及病理检查。结果:在16769人中,检出VCA-IgA阳性417人,EA-IgA阳性20人,鼻咽癌6例。鼻咽癌病人的VCA-IgA和EA-lgA均阳性,其几何平均滴度分别为1:113.1和1:28.3。检出的鼻咽癌病例全部为临床Ⅱ期。结论:鼻咽癌血清学普查对于早期发现鼻咽癌病人有着十分重要的作用。     

鼻咽癌普查中EB病毒IgG／EA抗体检测的应用

1978年我所曾应用间接免疫酶法检测人血清Epstein- Barr( EB)病毒的壳抗原免疫球蛋白 A抗体( Ig A/VCA抗体 )进行鼻咽癌普查 ( NPC) ,该法已广泛用于鼻咽癌血清学的早期诊断及预后判断[1] 。有文献报道[2 ] 鼻咽癌病人的抗 EB病毒早期抗原的免疫球蛋白 G抗体 ( Ig G/EA抗体 )阳性率可达90 %以上 ,我所在鼻咽癌普查中采用间接免疫酶法 ,检测 71 5 1人群血清的 Ig G/EA抗体 ,现报告如下。1　材料与方法1 .1　普查人群　 1 997年 1 0月至 1 998年 3月 ,我所对苍梧县对 2 0岁以上的职工、群众 71 5 1人进行普查。其中男性 435 9人 ,女…     

亚太地区肿瘤会议有关鼻咽癌的基础和临床研究

第十届亚太地区肿瘤会议共收到有关鼻咽癌的文章30篇,报告者大多为我国学者(包括香港和台湾),其他作者则来自日本、泰国、印度、意大利和荷兰等国。论文内容可归纳如下: EB病毒和鼻咽癌的关系闵华庆等报导对广东省鼻咽癌高、中、低发的5个点共123 087名健康人群进行了EB病毒血清学、鼻咽脱落细胞学、间接鼻咽镜以及鼻咽光导纤维镜检查并经活检等前瞻性观察,共发现了鼻咽癌126例。他们认为IgA/VCA抗体在正常人群中阳性率高,但1gA/VCA抗体的阳性人群中,鼻咽癌的发生     

EB病毒与鼻咽癌相关的前瞻性观察

1986—1990年我们对广东省鼻咽癌高、中、低发区的四会、中山、广州、湛江、汕头共123087名健康人群进行了包括EB病毒血清学、鼻咽脱落细胞学、间接鼻咽镜及鼻咽光纤镜、鼻咽活检在内的前瞻性观察。在这队列中共发现鼻咽癌126例。通过本研究我们发现:(一)、EB病毒IgA/VCA阳性人群中鼻咽癌检出率是阴性人群的40.7倍;但阴性不能完全排除鼻咽癌可能性(二),IgA/VCA抗体的出现可先于鼻咽癌确诊4—46个月。(三)、有下列指标之一者应被视为鼻咽癌的高危人群;①IgA/VCA≥1:80。②IgA/VCA、IgA/EA、DNase三项中任何两项阳性。③上述三项中任何一项滴度持续上升。对列入高然对象者应争取作鼻咽光导纤维镜检查,并在好发部位取活检以发现更多临床T_0或T_1患者。     

外周血和鼻咽组织EB病毒DNA检测对鼻咽癌诊断和防控的临床观察

目的探讨外周血和鼻咽组织EB病毒DNA检测对鼻咽癌诊断和防控的临床意义以及鼻咽腔冲洗对防控鼻咽癌的价值。方法选取2010年12月至2012年4月55例鼻咽癌患者为观察组,抽取同期55例健康者为对照组,采用EB病毒DNA PCR荧光定量检测技术检测外周血和鼻咽组织EB病毒DNA,比较鼻咽癌患者与健康者外周血和鼻咽组织EB病毒DNA检测结果。对另外1组67例EB病毒抗体阳性而鼻咽活检结果为阴性者进行鼻咽腔冲洗,比较治疗前、后EB病毒抗体检测结果。结果观察组患者外周血、鼻咽组织中EB病毒DNA阳性检出率均高于对照组健康者,差异均有统计学意义(均P<0.01)。经鼻咽腔冲洗治疗后,EB病毒抗体阳性者检测转阴率为19.4%,患者临床症状明显改善。结论鼻咽组织EB病毒DNA检测有助于鼻咽癌的临床诊断,对EB病毒抗体阳性者进行鼻咽腔冲洗治疗对于鼻咽癌的防控具有重要意义。     

自然人群413 164人鼻咽癌血清学普查

目的分析普查自然人群413 164人EB病毒壳抗原的免疫球蛋白A抗体(VCA-IgA)和早期抗原抗体(EA-IgA)阳性与性别、年龄及鼻咽癌检出关系.方法应用免疫酶法检测VCA-IgA和EA-IgA抗体,间接鼻咽镜检查,病理组织学诊断.结果普查自然人群413 164人检出VCA-IgA抗体阳性12 629人,阳性率3.06%,抗体阳性率高低与性别无关,与年龄高低呈正相关趋势.检出鼻咽癌174例,早期151例,早诊率86.78%,普查自然人群鼻咽癌检出率42.11/10万.鼻咽癌检出率高低与年龄呈正相关趋势.结论本法普查鼻咽癌可达提高早诊率目的,若普查重点能放在35岁以上人群意义更大.     

EB病毒抗体与鼻咽癌发病风险的前瞻性研究

[目的]探讨EB病毒抗体滴度变化与鼻咽癌发病风险的关系,为筛检高危人群提供依据.[方法] 1987～2007年对广东省四会市共18986名现场人群进行筛检,检测血清学EB病毒壳抗原免疫球蛋白(VCA/IgA)和早期抗原免疫球蛋白(EA/IgA)水平.采用Cox风险回归模型评估EB病毒抗体与鼻咽癌发病风险的关系.[结果] 1987～2007年共检出125例鼻咽癌.VCA/IgA和EA/IgA的血清阳性率分别为7.16％ (1318/18411)和0.24％ (45/18411).VCA/IgA阴性组鼻咽癌年龄调整发病率为29.4/10万人年,明显低于VCA/IgA阳性、EA/IgA阴性组(188.2/10万人年)和两者均阳性组(617.4/10万人年).与VCA/IgA阴性组相比,VCA/IgA阳性者抗体滴度越高,鼻咽癌发病风险越大.随访期间,EB病毒VCA/IgA抗体滴度升高者的鼻咽癌发病风险最高,在前5年的随访期间更为明显(调整HR=21.3,95％CI:7.1～64.1),抗体滴度降低者的发病风险最低(调整HR=1.5,95 ％CI:0.2～11.4).[结论]持续升高的VCA/IgA抗体滴度与鼻咽癌发病风险的增加明显相关,EB病毒VCA/IgA抗体阳性者是筛查的重点人群.     

鼻咽清毒颗粒加鼻渊舒口服液抑制鼻咽癌高危人群EB病毒VCA/IgA的临床观察

目的:观察鼻咽清毒颗粒加鼻渊舒口服液对鼻咽癌高危人群EB病毒壳抗原抗体VCA/IgA的抑制作用。方法:将136例鼻咽癌高危患者按就诊顺序分成实验组(鼻咽清毒颗粒加鼻渊舒口服液组)76例和对照组(鼻咽清毒颗粒组)60例。两组在治疗前均经电子鼻咽镜检查和鼻咽部活检排除有鼻咽癌。结果:实验组和对照组治疗前EB病毒VCA/IgA几何平均滴度分别为1∶38.04和1∶30.80,两组几何平均滴度基本一致,u=1.18,P=0.320。治疗后,实验组76例患者中痊愈42例(55.3%)、显效16例(21.0%)、有效10例(13.2%)及无效8例(10.5%),未见任何不良反应;对照组60例患者中痊愈10例(16.7%)、显效4例(6.6%)、有效10例(16.7%)及无效36例(60.0%)。两组疗效比较差异有统计学意义,u=4.2,P=0.000。治疗后,对照组VCA/IgA几何平均滴度降至1∶22.15,鼻咽清毒颗粒对EB病毒VCA/IgA滴度水平影响不大,u=1.34,P=0.220;而实验组VCA/IgA几何平均滴度降至1∶8.26,鼻咽清毒颗粒加用鼻渊舒口服液能显著性降低鼻咽癌高危人群EB病毒VCA/IgA滴度水平,u=8.92,P=0.000。结论:鼻咽清毒颗粒加用鼻渊舒口服液对鼻咽癌高危人群EB病毒VCA/IgA滴度水平有明显的抑制作用,有助于降低鼻咽癌的发病率。     

Serological mass survey for early detection of nasopharyngeal carcinoma in wuzhou city,china

A serological mass survey was carried out in Wuzhou City of the Guangxi Autonomous Region, China. Sera were collected from 12,932 persons between the ages of 40 and 59. The positive rate of VCA/IgA antibody-positive persons was 5.3%, but no EA/IgA antibody was found in sera from VCA/IgA-negative persons. Thirteen and nine nasopharyngeal carcinoma (NPC) patients were detected from the VCA/IgA and EA/IgA antibody-positive persons, respectively. With the present combination method the detection rate of NPC for 12,932 persons was 100.5/100,000 and for 680 VCA/IgA antibody-positive persons it was 1,900/100,000. Thus, the rate was twice and 37 times higher, respectively, than the annual incidence rate of NPC in persons of the same age group from 1975-1978 in Wuzhou City. Of 13 NPC patients, 9 were in stage 1(70%) and 4 in stage II (30%). Therefore, it is possible to reduce the mortality rate of NPC in Wuzhou City by radiotherapy of NPC patients in the early stage of the disease. The present results further suggest that EB virus is closely associated with NPC.     

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。      

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

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SERO-EPIDEMIOLOGICAL STUDIES OF EPSTEIN-BARR VIRUS(EBV) INFECTION BY TESTING ANTIBODIES AGAINST EBV SPECIFIC DNASE(EDAb) AS A METHOD FOR EARLY DETECTION OF NASOPHARYNGEAL CARCINOMA(NPC)

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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.     

鼻咽癌患者一级亲属不同性别人群EB病毒抗体和患病概率分析

目的:通过对散发性鼻咽癌患者一级亲属EB病毒感染和患病概率分析,了解遗传和性别因素对EB病毒抗体水平和患鼻咽癌概率的影响.方法:用ELISA法检测散发性鼻咽癌患者一级亲属(亲属组)和一般人群(对照组)血清EB病毒VCA/IgA和EBNA1/IgA抗体,统计不同人群抗体阳性率、鼻咽癌风险概率和癌检出率.结果:亲属组和对照组的VCA/IgA阳性率分别为6.78％和5.83％,EBNA1/IgA阳性率分别为6.10％和4.00％,抗体阳性率组间差异均无统计学意义(P＞0.05),其中男亲属组的阳性率高于男对照组(P＜0.05).男亲属组的鼻咽癌高危率大于男对照组(P＜0.05).在亲属组与对照组,VCA/IgA阳性率显示与性别无关(P＞0.05),而EBNA1/IgA阳性率和鼻咽癌高危率均表现为男性高于女性,P＜0.05.男亲属组癌检出率大于男对照组,P＜0.05;男对照组癌检出率大于女对照组,P＜0.05.结论:散发性鼻咽癌患者男性一级亲属EBNA1/IgA抗体阳性率和患鼻咽癌风险较一般男性高,而女性亲属以上指标与一般女性无差异.散发性鼻咽癌一级亲属中男性患鼻咽癌的风险高于女性.男性一级亲属鼻咽癌患病率高于一般人群,再次提示由血缘关系反映的遗传因素是鼻咽癌发病的主要原因.     

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.