上海地区人乳头瘤病毒基因芯片法分型检测的临床意义

doi:10.3969/j.issn.1673-8640.2015.06.013

摘要/Abstract

摘要： 目的

了解上海地区人乳头瘤病毒(HPV)感染情况及其亚型分布频率,探讨HPV感染亚型、单一感染和多重感染与宫颈上皮内病变的关系。

方法

选取846例门诊及体检妇女,收集宫颈上皮脱落细胞,采用基因芯片技术进行HPV 26种亚型的分型检测,同时进行超薄液基细胞学检测(TCT),对细胞学结果为较高级别病变的妇女进一步做阴道镜活检。

结果

846例研究对象中HPV总阳性率达29.55%,大多为单一高危型HPV感染;共检出HPV亚型24种,检出率排在前6位的是HPV52、58、16、53、51、55;HPV18、68和59等在单一感染和多重感染中的出现频率不一致;在高级别宫颈上皮内病变组[包括宫颈鳞状细胞癌或腺癌、宫颈上皮内瘤样病变(CIN)3、CIN2,简称为≥CIN2组]中共检出13种高危型HPV和1种低危型HPV,HPV16在≥CIN2组中的感染率为46.88%,远远高于低级别宫颈上皮内病变组(包括不明意义的非典型鳞状细胞增生、正常及CIN1,简称为<CIN2组)(9.63%, P<0.05)。

结论

上海地区HPV感染亚型以HPV52、58、16为最常见,但在≥CIN2组则以HPV16为最多,HPV16感染是最重要的导致高级别宫颈上皮病变的危险因素。

关键词: 人乳头瘤病毒, 宫颈上皮内瘤样病变, 基因芯片, 基因型

Abstract: Objective

To study the situation and genotype distribution of human papillomavirus(HPV) in Shanghai, and to investigate the relationships of HPV genotype, single-infection and multi-infection with the severity of cervical intraepithelial pathological changes.

Methods

Cervical epithelial cell samples were collected from 846 outpatients and healthy examination subjects and determined for HPV genotyping by gene chip technology and thin-prep cytology test(TCT). Biopsies under colposcopy were taken on subjects with abnormal cytology results.

Results

The HPV positive rate was 29.55%, and the most were high-risk HPV single-infection. A total of 24 types of HPV were detected, and the most prevalence types were HPV52, 58, 16, 53, 51 and 55 in turn. The prevalences of HPV18, HPV68 and HPV59 were different between in single-infection and in multi-infection. There were 13 types of high-risk HPV, and only one low-risk HPV was detected in high-grade cervical intraepithelial neoplasia (CIN) [including cervical squamous cell carcinoma or adenocarcinomas, CIN 3 and CIN2, as ≥CIN2]. The prevalence of HPV16 ≥CIN2 was 46.88%, which was a far higher proportion than in healthy subjects and in low-grade cervical intraepithelial pathological changes (including atypical squamous cell of undetermined significance, normal and CIN1, as<CIN2) (9.63%, P<0.05).

Conclusions

HPV52, 58 and 16 are the most popular types in Shanghai. HPV16 is popular in ≥CIN2 group. HPV16 is the most important predictor of high-grade cervical intraepithelial pathological changes.

Key words: Human papillomavirus, Cervical intraepithelial neoplasia, Gene chip, Genotype

中图分类号:

R446.5

缪应新, 甘洁民, 陈洁, 施泓, 姜文容, 赵虎. 上海地区人乳头瘤病毒基因芯片法分型检测的临床意义[J]. 检验医学, 2015, 30(6): 595-598.

MIAO Yingxin, GAN Jiemin, CHEN Jie, SHI Hong, JIANG Wenrong, ZHAO Hu. Clinical significance of human papillomavirus genotyping by gene chip technology in Shanghai[J]. Laboratory Medicine, 2015, 30(6): 595-598.

图/表 2

参考文献 17

[1]	STEVENS MP,GARLAND SM,TAN JH,et al.HPV genotype prevalence in women with abnormal pap smears in Melbourne,Australia[J]. J Med Virol,2009,81(7):1283-1291.
[2]	HOORY T,MONIE A,GRAVITT P,et al.Molecular epidemiology of human papillomavirus[J]. J Formos Med Assoc,2008,107(3):198-217.
[3]	ZUR HAUSEN H.The search for infectious causes of human cancers: where and why (Nobel lecture)[J]. Angew Chem Int Ed Engl,2009,48(32):5798-5808.
[4]	SANKARANARAYANAN R,NENE BM,SHASTRI SS,et al.HPV screening for cervical cancer in rural India[J]. N Engl J Med,2009,360(14):1385-1394.
[5]	MAYRAND MH,DUARTE-FRANCO E,RODRIGUES I,et al.Human papillomavirus DNA versus papanicolaou screening tests for cervical cancer[J]. N Engl J Med,2007,357(16):1579-1588.
[6]	和晓利,刘洪倩,何斌,等.基于基因芯片技术的人乳头瘤病毒分型检测方法及应用评价[J]. 四川大学学报:医学版,2013,44(4):641-645.
[7]	MUÑOZ N,BOSCH FX,DE SANJOSÉ S,et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer[J]. N Engl J Med,2003,348(6):518-527.
[8]	BOSCH FX,MANOS MM,MUÑOZ N,et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective international biological study on cervical cancer (IBSCC) study group[J]. J Natl Cancer Inst,1995,87(11):796-802.
[9]	CLIFFORD GM,SMITH JS,PLUMMER M,et al.Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis[J]. Br J Cancer,2003,88(1):63-73.
[10]	HONG D,YE F,CHEN H,et al.Distribution of human papillomavirus genotypes in the patients with cervical carcinoma and its precursors in Zhejiang Province, China[J]. Int J Gynecol Cancer,2008,18(1):104-109.
[11]	WRIGHT TC Jr,MASSAD LS,DUNTON CJ,et al.2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests[J]. Am J Obstet Gynecol,2007,197(4):346-355.
[12]	RIBEIRO AA, FIGUEIREDO ALVES RR, COSTA MC, et al.Association between HPV types and species groups and cervical neoplasia from a high-risk area for cervical cancer,Goiania,Brazil[J]. Int J Gynecol Pathol,2011,30(3):288-294.
[13]	TROTTIER H,MAHMUD S,COSTA MC,et al.Human papillomavirus infections with multiple types and risk of cervical neoplasia[J]. Cancer Epidemiol Biomarkers Prev,2006,15(7):1274-1280.
[14]	NIELSEN A,KJAER SK,MUNK C,et al.Type-specific HPV infection and multiple HPV types: prevalence and risk factor profile in nearly 12 000 younger and older Danish women[J]. Sex Transm Dis,2008,35(3):276-282.
[15]	BACHTIARY B,OBERMAIR A,DREIER B,et al.Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer[J]. Int J Cancer, 2002,102(3):237-243.
[16]	GARGIULO F,DE FRANCESCO MA,SCHREIBER C,et al.Prevalence and distribution of single and multiple HPV infections in cytologically abnormal cervical samples from Italian women[J]. Virus Res,2007,125(2):176-182.
[17]	SCHMITT M,DONDOG B,WATERBOER T,et al.Abundance of multiple high-risk human papillomavirus (HPV) infections found in cervical cells analyzed by use of an ultrasensitive HPV genotyping assay[J]. J Clin Microbiol,2010,48(1):143-149.

年龄(岁)	例数	HPV阳性者	≥CIN2者
20~30	124(14.66)	41(16.40)	0(0.00)
31~40	258(30.50)	78(31.20)	7(21.88)
41~50	210(24.82)	63(25.20)	15(46.88)^*#
51~60	175(20.69)	46(18.40)	7(21.88)
61~80	79(9.34)	22(8.80)	3(9.37)
合计	846	250	32

年龄(岁)	例数	HPV阳性者	≥CIN2者
20~30	124(14.66)	41(16.40)	0(0.00)
31~40	258(30.50)	78(31.20)	7(21.88)
41~50	210(24.82)	63(25.20)	15(46.88)^*#
51~60	175(20.69)	46(18.40)	7(21.88)
61~80	79(9.34)	22(8.80)	3(9.37)
合计	846	250	32