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高危型人乳头瘤病毒基因分型聚合酶链反应检测作为宫颈癌及癌前病变早期筛查手段

[High-risk HPV genotyping PCR testing as a means of cervical cancer and precancerous lesions early screening].

作者信息

Ma Li, Cong Xiao, Bian Meilu, Shi Mai, Wang Xiuhong, Liu Jun, Liu Haiyan

机构信息

Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing 100029, China.

Email:

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2015 Apr;50(4):246-52.

PMID:26080934
Abstract

OBJECTIVE

To explored high-risk HPV genotyping PCR testing whether as a feasible means for the early screening of cervical cancer and precancerous lesions.

METHODS

From January 2013 to June 2014, 15,192 outpatients in China-Japan Friendship Hospital voluntary were tested by high-risk type HPV genotyping PCR. The average age of them were (33±8) years old. High-risk HPV types genotyping PCR tested by fluorescence PCR technology, in which 13 kinds of high-risk HPV subtypes were detected, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. A total of 4,315 cases of them were tested by the liquid-based cytology (LCT), among them with positive of high-risk HPV genotyping tested by PCR (n=2,366) were biopsy under colposcope (648 cases) in those LCT results were positive or LCT negative but HPV16 positive or LCT negative but had the clear clinical symptoms or and non-HPV16 positive but with clear clinical symptoms. (1) Analysis high-risk HPV infection status of 15 192 women. (2) As the pathological diagnosis was the gold standard in the diagnosis of cervical lesions, analysis of the relationship among high-risk HPV infection, virus loads and cervical lesions. (3) To evaluated the value of high-risk HPV genotyping PCR tested method in screening of cervical cancer and precancerous lesions.

RESULTS

⑴ Of 15,192 cases tested by high-risk HPV genotyping PCR, 2,366 cases were HPV positive (HPV infection), the overall infection rate was 15.57% (2,366/15,192), in which a single subtype of HPV infection in 1,767 cases, infection rate was 11.63% (1,767/15,192), and multiple subtypes of HPV infection (two and more subtypes HPV infection) in 599 cases, infection rate was 3.94% (599/15,192). The HPV16, 52 and 58 infections were the most common HPV subtypes in 13 subtypes, the infection rate was 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively. (2) The most relevant subtypes with cervical intraepithelial neoplasia (CIN) II and even higher lesion were HPV16, 52 and 58, accounted for 57.7% (154/267) of all above CIN II lesions. The most relevant subtype with the cervical glandular intraepithelial neoplasia (CGIN) II or above lesions was HPV18, 3 cases with CGIN II or above lesions were all single HPV18 infection. The pathologic examination positive percentage of patients which HPV virus loads≤10(3) copys/10(4) cells was 18.2% (25/137), while the pathologic examination positive proportion was 33.3% (247/742) which HPV virus loads≥10(4) copys/10(4) cells, there was statistically significant difference between them (χ2=27.06, P=0.000). (3) Sensitivity, specificity, positive predictive value and negative predictive value for detection of CIN II or above using HPV genotyping PCR were 96.11%, 85.76%, 30.94% and 99.70%, respectively.

CONCLUSIONS

There were a guiding significance for high-risk HPV genotyping PCR tested in screening of cervical cancer and precancerous lesion. HPV16, 52 and 58 were related to the severe cervical squamous epithelial lesions, while HPV18 was related to cervical severe glandular cell pathological changes. HPV genotyping is feasible and economical as the first choice of opportunistic screening in tertiary hospitals.

摘要

目的

探讨高危型人乳头瘤病毒(HPV)基因分型PCR检测作为宫颈癌及癌前病变早期筛查的可行性方法。

方法

2013年1月至2014年6月,中日友好医院15192例门诊自愿就诊者接受高危型HPV基因分型PCR检测,平均年龄(33±8)岁。采用荧光PCR技术进行高危型HPV基因分型PCR检测,检测13种高危HPV亚型,包括HPV16、18、31、33、35、39、45、51、52、56、58、59和68。其中4315例同时行液基细胞学(LCT)检测,对PCR检测高危HPV基因分型阳性者(n = 2366),LCT结果阳性或LCT阴性但HPV16阳性或LCT阴性但有明确临床症状或非HPV16阳性但有明确临床症状者共648例行阴道镜下活检。(1)分析15192例女性高危HPV感染状况。(2)以病理诊断为宫颈病变诊断的金标准,分析高危HPV感染、病毒载量与宫颈病变的关系。(3)评估高危HPV基因分型PCR检测方法在宫颈癌及癌前病变筛查中的价值。

结果

⑴15192例接受高危HPV基因分型PCR检测者中,2366例HPV阳性(HPV感染),总感染率为15.57%(2366/15192),其中单一亚型HPV感染1767例,感染率为11.63%(1767/15192),多重亚型HPV感染(两种及以上亚型HPV感染)599例,感染率为3.94%(599/15192)。HPV16、52和58感染是13种亚型中最常见的HPV亚型,感染率分别为3.95%(600/15192)、2.86%(435/15192)和2.67%(406/15192)。(2)与宫颈上皮内瘤变(CIN)Ⅱ及以上病变最相关的亚型为HPV16、52和58,占所有上述CINⅡ病变的57.7%(154/267)。与宫颈腺上皮内瘤变(CGIN)Ⅱ及以上病变最相关的亚型为HPV18,3例CGINⅡ及以上病变均为单一HPV18感染。HPV病毒载量≤10³拷贝/10⁴细胞患者病理检查阳性率为18.2%(25/137),而HPV病毒载量≥10⁴拷贝/10⁴细胞患者病理检查阳性率为33.3%(247/742),两者差异有统计学意义(χ² = 27.06,P = 0.000)。(3)HPV基因分型PCR检测CINⅡ及以上病变的灵敏度、特异度、阳性预测值和阴性预测值分别为96.11%、85.76%、30.94%和99.70%。

结论

高危HPV基因分型PCR检测对宫颈癌及癌前病变筛查有指导意义。HPV16、52和58与宫颈重度鳞状上皮病变相关,而HPV18与宫颈重度腺细胞病变相关。HPV基因分型作为三级医院机会性筛查的首选方法可行且经济。

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