宫颈癌患者血清中HPV-E7检测的临床意义

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许晓峰, 卢仁泉, 沈烨红, 郭林. 宫颈癌患者血清中HPV-E7检测的临床意义. 25(5): 355-356
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《检验医学》编辑部

宫颈癌患者血清中HPV-E7检测的临床意义

许晓峰, 卢仁泉, 沈烨红, 郭林

复旦大学附属肿瘤医院检验科, 上海 200032

作者简介：许晓峰,男,1976年生,学士,主管技师,主要从事临床免疫检验工作。

摘要

关键词: E7蛋白; 人乳头瘤病毒; 酶联免疫吸附试验; 宫颈癌

中图分类号:R446.62 文献标志码:B 文章编号:1673-8640(2010)05-0355-02

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宫颈癌是最常见的女性恶性肿瘤之一, 其与人乳头瘤病毒(Human papilloma virus, HPV)关系越来越被研究者和临床医生所重视, 已经明确90%的宫颈癌是由HPV持续感染引起的, 而其中高危型HPV-E7蛋白是HPV诱发宫颈癌的一个重要原因。本研究用酶联免疫吸附试验(ELISA)测定了74例宫颈癌患者、20例宫颈上皮内瘤变(cervical intraepithelial neoplasia , CIN)患者及20名正常人血清中HPV-E7蛋白含量, 并以血清肿瘤标志物鳞状细胞癌抗原(squamous cell carcinoma antigen , SCCA)、癌胚抗原(carcinoembbryonic antigen, CEA)作为对照。

一、材料和方法

1.研究对象为复旦大学附属肿瘤医院2006至2008年住院或门诊患者, 其中宫颈癌患者74例, 年龄31~74岁, 平均46.7岁, 按1994年国际妇产科联盟FIGO分期:Ⅰ 期18例, Ⅱ 期20例, Ⅲ 期18例, Ⅳ 期18例; CIN患者20例, 年龄28~62岁, 平均44.3岁, CIN Ⅰ ~Ⅱ 级18例, CIN Ⅲ 级2例。所有病例经病理确诊。20名正常对照为女性健康体检者, 年龄23~55岁, 平均年龄47.5岁。

2.方法抽取空腹静脉血, 分离血清, -20 ℃保存待测。HPV-E7、SCCA、CEA测定采用ELISA, HPV-E7试剂盒由美国ADL公司出品; SCCA试剂盒由瑞士康乃格公司出品; CEA试剂盒由上海科华生物工程股份有限公司出品。仪器为西班牙产TRITURUS全自动酶免仪。根据试剂盒说明书, HPV-E7、SCCA及CEA临界参考值分别为30 IU/L、1.5 μ g/L、15 μ g/L。

3.统计学方法采用SPSS 10.0软件进行数据处理, 所得数据以 $\begin{matrix} \bar{x} \end{matrix}$ ± s表示, 多组均数比较采用方差分析, 两两之间比较用q检验, 率的比较采用χ ²检验。

二、结果

1. 3组血清中肿瘤标志物水平比较宫颈癌组3种肿瘤标志物水平高于CIN组和对照组, 差异均有统计学意义(P< 0.05), 而CIN组和正常对照组之间差异无统计学意义(P> 0.05)。见表1。

表1 血清中3种肿瘤标志物水平比较(

\begin{matrix} \bar{x} \end{matrix}

± s)

组别	例数	HPV-E7(IU/L)	SCCA(μ g/L)	CEA(μ g/L)
宫颈癌组	74	43.56± 31.07^{* #}	6.71± 4.18^{* #}	4.01± 3.11 ^{* #}
CIN组	20	25.45± 15.26	0.67± 0.43	1.84± 0.95
对照组	20	26.68± 3.17	0.48± 0.30	1.77± 1.65

注:与对照组比较, * P< 0.05; 与CIN组比较, #P< 0.05

表1 血清中3种肿瘤标志物水平比较(

\begin{matrix} \bar{x} \end{matrix}

± s)

2.宫颈癌组3种肿瘤标志物单项检测比较以实际检测值分别计算3种肿瘤标志物的敏感性、特异性、准确性。与SCCA(24.4%、90.7%、47.9%)、CEA(21.8%、88.4%、45.5%)比较, HPV-E7敏感性、特异性和准确性均最高, 分别为48.7%、93.0%、64.5%。

3.不同临床分期的宫颈癌患者3种血清肿瘤标志物阳性检出率 Ⅱ 、Ⅲ 、Ⅳ 期宫颈癌患者HPV-E7(45.0%、65.0%、77.8%)、SCCA(10.0%、35.0%、55.6%)和CEA(15.0%、30.0%、44.4%) 阳性检出率高于I期患者(10.0%、0.0%、0.0%), 差异有统计学意义(P< 0.05), Ⅲ 、Ⅳ 期宫颈癌患者HPV-E7阳性检出率高于Ⅱ 期患者, 差异有统计学意义(P< 0.05)。

三、讨论

大部分HPV感染无临床症状或亚临床感染, 持续携带HPV提示感染者处于继发癌前病变的高度危险中。有研究表明, 高危型HPV-E7感染在宫颈癌发病过程中起着重要作用^[1]。

本研究显示, 与正常对照组及CIN组相比, 宫颈癌患者血清中HPV-E7浓度明显偏高, 与文献[2]描述相符。宫颈癌患者血清中HPV-E7敏感性为48.7%, 特异性为93.0%, 准确性为64.5%, 与常见宫颈癌肿瘤标志SCCA和CEA相比较, 均有不同程度的提高, 表明HPV-E7可以成为宫颈癌一种较好的、特异性的肿瘤标志物。本研究还发现, 治疗前宫颈癌HPV-E7、SCCA和CEA阳性检出率皆随临床FIGO分期增加而升高, 晚期宫颈癌(Ⅲ 、Ⅳ 期)与早期宫颈癌(Ⅰ 、Ⅱ 期)相比, 差异具有统计学意义(P< 0.05)。HPV-E7 ELISA检测作为补充和替代传统细胞学检查的一种手段, 采集方便, 有望成为及时诊断和监测宫颈癌的一种新的有效指标。

The authors have declared that no competing interests exist.

参考文献

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[1]	Yugawa T, Kiyono T. Molecular mechanisms of cervical carci-nogenesis by high-risk Human papillomaviruses: novel functions of E6 and E7 oncoproteins[J]. Rev Med Virol, 2009, 19(2): 97-113. [本文引用:1] [JCR: 7.615]
[2]	Ravaggi A, Romani C, Pasinetti B, et al. Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients[J]. Arch Virol, 2006, 151(10): 1899-1916. [本文引用:1] [JCR: 2.03]

2009

7.615

0.0

. 2009, 19(2):97-113

Molecular mechanisms of cervical carcinogenesis by high-risk human papillomaviruses: novel functions of E6 and E7 oncoproteins

Takashi Yugawa andTohru Kiyono *

Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan * Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

> Over the last two decades, since the initial discovery of human papillomavirus (HPV) type 16 and 18 DNAs in cervical cancers by Dr. Harald zur Hausen (winner of the Nobel Prize in Physiology or Medicine, 2008), the HPVs have been well characterised as causative agents for cervical cancer. Viral DNA from a specific group of HPVs can be detected in at least 90% of all cervical cancers and two viral genes, E6 and E7, are invariably expressed in HPV-positive cervical cancer cells. Their gene products are known to inactivate the major tumour suppressors, p53 and retinoblastoma protein (pRB), respectively. In addition, one function of E6 is to activate telomerase, and E6 and E7 cooperate to effectively immortalise human primary epithelial cells. Though expression of E6 and E7 is itself not sufficient for cancer development, it seems to be either directly or indirectly involved in every stage of multi-step carcinogenesis. Epidemiological and biological studies suggest the potential efficacy of prophylactic vaccines to prevent genital HPV infection as an anti-cancer strategy. However, given the widespread nature of HPV infection and unresolved issues about the duration and type specificity of the currently available HPV vaccines, it is crucial that molecular details of the natural history of HPV infection as well as the biological activities of the viral oncoproteins be elucidated in order to provide the basis for development of new therapeutic strategies against HPV-associated malignancies. This review highlights novel functions of E6 and E7 as well as the molecular mechanisms of HPV-induced carcinogenesis. Copyright © 2009 John Wiley & Sons, Ltd.

... 有研究表明,高危型HPV-E7感染在宫颈癌发病过程中起着重要作用^[1] ...

2006

2.03

0.0

. 2006, 151(10):1899-1916 DOI:10.1007/s00705-006-0787-y

Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients

1.University of Brescia Division of Gynecologic Oncology Brescia Italy 2.Spedali Civili di Brescia Department of Obstetrics and Gynecology Brescia Italy 3.Spedali Civili di Brescia Department of Pathology Brescia Italy 4.University of Brescia Section of Medical Statistics and Biometry, Department of Biomedical Sciences and Biotechnology Brescia Italy 5.University of Arkansas for Medical Sciences Division of Gynecologic Oncology Little Rock AR U.S.A.

Human papillomaviruses (HPVs), particularly HPV-16/18, are linked to cervical cancer development. Full-length, recombinant HPV-16/18 E7 oncoproteins were used in a new streptavidin-biotin capture ELISA method to investigate anti-HPV E7 antibody prevalence in serum. Sera from 99 healthy women, 70 cervical cancer patients, and 30 patients with cervical pre-invasive neoplasia were analyzed. Anti-HPV-16/18 E7 positivity was found in 53% of cervical cancer patients, in 40% with cervical pre-invasive neoplasia, and in 8% of healthy women. Serum samples from 12 cervical cancer patients were obtained at different time intervals during the treatment. Eleven out of 12 showed a correspondence between HPV-E7 antibody levels (decreasing versus increasing) and the type of response (clinically complete or partial response versus progression or stable disease) at each serological evaluation. Five patients with recurrent HPV-16/18-positive cervical carcinoma were analyzed before and after vaccination with HPV-16/18 E7-pulsed autologous dendritic cells; anti-HPV-16/18 E7 positivity was found in 3 out of 5 women. In conclusion, this assay could potentially be used as an adjunctive tool to monitor the type of response to treatment and possibly to detect antibody induction in cervical cancer patients after vaccination, as a potential marker to evaluate its efficacy.