共查询到18条相似文献,搜索用时 203 毫秒
1.
目的:分析青岛地区妇女不同宫颈病变组织中人乳头瘤病毒16型(HPV16)上游调控区(URR)和E6基因序列多态性,以及序列变异与宫颈病变的相关性。方法:采用聚合酶链式反应(PCR)技术检测120例宫颈癌及254例宫颈上皮内瘤变(CIN)标本,筛选出HPV16阳性标本,进而扩增出HPV16URR和E6基因,PCR产物纯化后测序,与德国HPV标准株进行对比分析。结果:URR测序结果发现了19个突变位点,所有标本在7521位点均发生了G→A突变;63.30%(69/109)标本中检测到24,7730和7842的联合突变,为另一突变热点。E6测序结果共发现17个突变位点,突变热点为178位点(D25E),其在宫颈癌组、CINⅢ组和CINⅡ组的比例分别为61.11%(44/72)、62.00%(31/50)和50.00%(16/32),3组的差异无统计学意义(P=0.499)。仅观察到6例350位点突变(L83V)。亚洲型(AS)是最多见的突变类型,在154例HPV16阳性标本中占59.09%,其次为E-P原型(33.12%)。结论:青岛地区妇女宫颈病变组织中HPV16URR突变热点为nt7521以及nt24、nt7730和nt7842的联合突变。HPV16E6突变热点为nt178,这些突变热点可能与癌前病变的进展有密切关系。AS型和原型是青岛地区宫颈病变组织中两种主要的HPV16分支。 相似文献
2.
目的:探讨HPV E6/E7 mRNA、p16/Ki67检测在宫颈细胞学检查为意义不明确的不典型鳞状细胞(ASCUS)中的诊断价值。方法:回顾分析2015年12月至2017年5月在郑州大学第三附属医院就诊的液基薄层细胞学检查(TCT)结果为ASCUS,并行阴道镜下宫颈组织活检的患者200例。应用杂交捕获技术(HC2)和支链DNA技术(b DNA)行HPV DNA、HPV E6/E7 mRNA检测。免疫组化法检测宫颈组织中p16/Ki67表达。结果:宫颈高级别病变组(包括CIN2,CIN3,宫颈癌,简称CIN2+)中p16/Ki67、HPV E6/E7mRNA的阳性率与炎症/CIN1组比较,差异有统计学意义(χ2=31. 952,P=0. 000;χ2=11.231,P=0.001),且p16/Ki67表达与CIN2+具有一致性(kappa=0.400,P=0.000)。炎症/CIN1组中,HPV E6/E7 mRNA检测与p16/Ki67检测结果间的差异有统计学意义(P=0.000),但在CIN2+中两者差异无统计学意义(P=0.375)。ROC曲线分析p16/Ki67检测、HPV E6/E7 mRNA检测诊断CIN2+的准确性分别为(AUC=0.800,0.625),均高于HPV DNA检测(AUC=0.579)。结论:HPV E6/E7 mRNA、p16/Ki67表达与宫颈高级别病变密切相关,HPV E6/E7 mRNA检测可望代替HPV DNA成为分流ASCUS的一种有效手段,而p16/Ki67与宫颈高级别病变显著一致,可辅助用于ASCUS患者宫颈组织的病理诊断。 相似文献
3.
宫颈癌及其癌前病变组织中FHIT蛋白异常表达与HPV16E6、HPV16E7蛋白表达的相关性 总被引:1,自引:0,他引:1
目的 探讨宫颈癌中三联脆组(FHIT)蛋白表达与HPV16 E6、E7蛋白表达的相关性.方法 采用免疫组化SP法对四川大学华西第二医院1999年1月至2003年2月的15例正常宫颈、25例宫颈上皮内瘤变(CIN)以及61例浸润性宫颈鳞癌组织标本进行FHIT蛋白、HPV16E6、HPV16 E7蛋白表达的检测.结果 (1)在正常宫颈上皮、CINI~II、CINⅢ及浸润性宫颈鳞癌中,FHIT 蛋白阳性表达率分别为100%(15/15)、71.43%(10/14)、36.36%(4/11)、14.75%(9/61),P<0.05;HPV16E6蛋白阳性表达率分剐为0(0/15)、7.14%(1/14)、36.36%(4/11)、59.02%(36/61),P<0.05;HPV16E7蛋白阳性表达率分别为20.00%(3/15)、42.86%(6/14)、63.64%(7/11)、57.38%(35/61),P>0.05.(2) 宫颈病变组织中FHIT蛋白的阳性表达与HPV16E6蛋白阳性表达呈负相关(P<0.0l,r=-0.449),与HPV16E7蛋白表达无相关性(P>0.05).结论 宫颈癌中FHIT 蛋白的异常表达与HPV16 E6蛋白表达有关,FHIT蛋白和HPV16E6蛋白的联合检测可能可作为宫颈癌前病变转归的指标. 相似文献
4.
目的:探讨山东省青岛地区不同宫颈病变组织中人乳头瘤病毒16型(HPV16)E2基因序列多态性,以及序列变异与不同宫颈病变的关系。方法:提取257例宫颈脱落细胞及宫颈癌组织DNA,PCR进行HPV分型,其中HPV16阳性标本扩增E2基因,测定PCR产物序列。通过DNAStar生物软件进行核苷酸和氨基酸序列分析。结果:共检测出11个碱基突变位点,其中10个导致氨基酸的改变,突变热点为nt3410(63.2%),nt3159(55.9%),nt3249(55.9%)。统计学分析显示,各个位点的突变与不同级别宫颈病变之间均无相关性(P>0.05)。宫颈癌标本中基因整合率为[65%(14/40)],远高于CINⅢ的整合率[14%(6/43)](P<0.001)。结论:青岛地区HPV16 E2基因存在多个位点的突变,且发现G2828A,T3274G,T3384C,T3524C为青岛地区特异性突变,这些位点的突变可能与高度上皮内瘤变和浸润性宫颈癌的发生和发展有关。 相似文献
5.
《现代妇产科进展》2020,(9)
目的:探讨HPV E6/E7 mRNA检测在LBC-/HPV+女性临床管理中的应用价值。方法:收集2017年12月至2019年9月在临沂市人民医院自愿接受液基细胞学(LBC)联合HR-HPV DNA(包含HPV16/18分型)或HPV E6/E7 mRNA检测进行宫颈癌筛查,结果为LBC-/HPV+且后续转诊阴道镜及组织病理学检查患者628例,以病理诊断结果为金标准,分析比较两种HPV检测方法对LBC-/HPV+患者人群发生高级别及以上宫颈病变(≥HSIL)的风险预测能力。结果:628例LBC-/HPV+患者中,共检出≥HSIL患者80例(12.74%),其中以30~39岁组检出率最高(17.89%)。490例HR-HPV DNA阳性患者≥HSIL总检出率为10.00%(49/490),双+组检出率最高(14.89%,14/94);138例HPV E6/E7 mRNA阳性患者≥HSIL总检出率为22.46%(31/138),16/18/45+组检出率最高(37.78%,17/45)。HPV E6/E7 mRNA阳性组发生≥HSIL的相对危险度(RR值)是HR-HPV DNA阳性组的2.246倍(95%CI为1.493~3.379);16/18/45+组发生≥HSIL的RR值是16/18+组患者的3.169倍(95%CI为1.786~5.622);HPV E6/E7 mRNA其余11型+组发生≥HSIL的RR值是HR-HPV DNA其余12型+组的2.170倍(95%CI为1.115~4.222),差异均有统计学意义(P0.05)。结论:HPV E6/E7 mRNA检测尤其是16/18/45分型检测是LBC-/HPV+患者人群发生≥HSIL的有效风险预测指标,其评价效能优于包含HPV16/18分型的HR-HPV DNA检测;HPV E6/E7 mRNA有望作为HR-HPV DNA阳性但16/18分型阴性患者的进一步分流指标。 相似文献
6.
目的探讨人乳头瘤病毒(HPV)E6/E7 m RNA检测在女性宫颈疾病筛查中的作用。方法选取2016年9月至2017年9月贵州医科大学附属医院妇产科门诊和住院部就诊的HPV阳性感染者287例,其中宫颈疾病患者267例[包括宫颈炎、宫颈上皮内瘤变(CIN)Ⅰ~Ⅲ、宫颈癌],阳性感染者中体检无疾病表现及病理学检查无宫颈病变者20例。取患者宫颈脱落细胞用支链DNA技术(简称b-DNA技术)检测高危HPV E6/E7 m RNA,患者同时行宫颈液基薄层细胞检测和HPV分型检测,对不同年龄、HPV分型、阴道细胞学分型(简称TBS分型)及疾病分级的HPV E6/E7 m RNA的诊断价值进行效能分析。结果在不同年龄段内E6/E7阳性和阴性所占比例差异有统计学意义,P0.05,在年龄组≤30岁组和50~60岁组,E6/E7阳性者所占比例最大,分别为85.40%和84.40%;而HPV E6/E7m RNA拷贝数在不同年龄组内差异没有统计学意义。E6/E7结果在单一感染和混合感染,以及单一感染和多重感染间差异无统计学意义;在不同感染型别中,只有HPV 16型随病变严重程度的增加其感染率呈递增趋势(P0.05),其余HPV型与病变严重程度无明显相关性(P0.05)。不同疾病分组间,E6/E7阳性率的分布差异有统计学意义,表现为无宫颈病变组(0)宫颈炎(15.60%)CINⅠ(86.20%)CINⅡ(93.00%)CINⅢ(96.50%)宫颈癌(100.00%),P0.05;E6/E7拷贝数表达差异有统计学意义,表现为宫颈炎1773.89(936.54)CINⅠ4997.74(10 439.75)CINⅡ52 655.02(38 495.10)CINⅢ72 300.12(38 298.57)宫颈癌121 616.68(34 348.59),P0.05。结论在宫颈疾病中检测高危型HPVE6/E7 m RNA的转录对女性宫颈癌高危人群的筛查和诊治具有重要的价值,或可作为进一步分流HPV阳性病人的方法。 相似文献
7.
目的:检测湖北地区HPV16阳性宫颈标本E2基因碳端(C)、铰链区(H)、氮端(N)的缺失状态,探讨其与CIN及宫颈癌的关系。方法:将122例宫颈标本按病变程度分为宫颈癌组、CINⅡ~Ⅲ组、对照组。应用多重聚合酶链反应(PCR)将各组HPV16感染标本E2基因的C、H、N分别与E6基因同时扩增,检测E2基因各区域的缺失状态,并应用Scion Image4.0软件半定量分析E2、E6基因条带灰度值,判断HPV DNA的整合状态。结果:宫颈癌组E2基因C、H、N缺失率分别是22.5%,50%,77.5%;CIN组为30.77%,69.23%,92.31%;对照组为9.09%,27.27%,27.27%。E2基因C、H缺失率在3组的任两组间比较无统计学差异(P0.05),而E2基因N端缺失率在宫颈癌组与对照组之间及CIN组与对照组之间差异有统计学意义(P均0.01)。结论:HPV16病毒E2基因N端缺失状态与CIN及宫颈癌有内在关系。在检测HPV感染同时检测E2基因N端缺失状态,对间接判断预后及指导后续治疗有重要意义。 相似文献
8.
《中国妇产科临床杂志》2015,(4)
目的探讨异常宫颈细胞学患者中检测人乳头瘤病毒(HPV)E6/E7mRNA的临床意义。方法对4 681例妇女行宫颈细胞学检查,≥ASC-US行阴道镜活检及病理学诊断;对78例活检患者采用分支链DNA信号放大技术检测HPVE6/E7 mRNA。结果4 681例妇女中,宫颈细胞学阳性78例(1.67%,78/4 681)。78例患者活检病理诊断:慢性宫颈炎14例,CIN1级36例,CIN2/3级23例,鳞癌5例;HPV E6/E7mRNA的总阳性率为80.77%(63/78),其中慢性宫颈炎组、CIN1组、CIN2/3组和鳞癌组阳性率分别为42.86%(6/14)、86.11%(31/36)、91.30%(21/23)和5/5,HPV E6/E7 mRNA中位拷贝数分别为1134.81、3788.32、8 943.71和262 662.19。结论 HPV E6/E7mRNA阳性率及拷贝值随宫颈病变级别升高逐渐增高,可作为评估宫颈癌前病变和宫颈癌的指标。 相似文献
9.
目的探讨山东省青岛地区妇女宫颈癌组织中人乳头瘤病毒16型(HPV16)上游调控区(URR)和E6基因序列多态性,病毒主要分支,以及他们与宫颈癌的相关性。方法从43例HPV16阳性宫颈癌组织中提取DNA,扩增URR及E6基因,进行序列测定。通过DNASTAR生物软件进行核苷酸和氨基酸序列的分析。结果所有标本URR测序结果均发生了G7521A位点突变;26例(60.5%)宫颈癌组织中检测到核苷酸位点C24T,A7730C和G7842A的联合突变,为另一突变热点。E6测序结果发现突变热点为T178G(D25E),突变率为65.1%(28/43);仅1例T350G突变(L83V)。AS型是最多见的病毒突变类型,占65.1%(28/43),其次为野生型(E-P)23.3%(10/43)。结论青岛地区妇女宫颈癌组织中HPV16URR突变热点为G7521A以及C24T,A7730C和G7842A的联合突变。HPV16E6突变热点为T178G,这些突变热点可能与宫颈癌发生发展有密切关系。AS和E-P原型是青岛地区宫颈癌组织中两种主要的HPV16分支。 相似文献
10.
宫颈癌及癌前病变组织中Notch1及HPV16 E6/E7表达的研究 总被引:12,自引:0,他引:12
目的 探讨Notch1受体和人乳头瘤病毒16感染在宫颈癌前病变和宫颈癌发生发展中的作用。方法 采用免疫组化SP法检测18例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和35例宫颈癌标本中Notch1受体及HPV16E6/E7蛋白的表达,以34例正常宫颈组织及慢性宫颈炎组织作为对照。比较各组间Notch1及HPV16E6/E7表达的差异,并分析Notch1与HPV16E6/E7表达的关系。结果 Notch1蛋白在细胞胞浆、胞核及胞膜中表达,HPV16E6/E7在细胞核中表达。从对照组到CIN组到宫颈癌组,Notch1及HPV16E6/E7的表达均逐渐增强(P〈0.01)。Notch1的阳性表达与宫颈癌不同分期、分化程度、淋巴结是否转移无关(P〉0.05)。在宫颈癌组中Notch1与HPV16E6/E7的表达均呈正相关性(P〈0.01)。结论 Notch1表达与HPV16E6/E7感染可能与CIN及宫颈癌的发生密切相关,两者在宫颈癌的发病机制中可能协同发挥作用。 相似文献
11.
Radhakrishna Pillai M Sreevidya S Pollock BH Jayaprakash PG Herman B 《Gynecologic oncology》2002,87(3):268-273
OBJECTIVES: Human papillomavirus type 16 is a causative factor for development of cervical cancer. The E6 and E7 genes of HPV 16 are critical to the process of immortalization and transformation of host cells. Recent reports suggest that variants of these two genes may contribute to the risk of malignant progression of cancer in the uterine cervix. However, no data exist on sequence variations of HPV 16 E6 and E7 genes that may exist in India. Therefore, we examined intratype variations in the E6 and E7 viral genes in DNA isolated from HPV 16-positive cervical scrapes and biopsies. METHODS: The open reading frames of the E6 and E7 genes were amplified by PCR and then directly sequenced by the fluorescent dye dideoxy termination method.Results. In addition to the prototype E6 gene sequence, five sets of mutations of the E6 gene were identified. The European prototype (350T) was detected in 9.1% of the study group while the European variant (350G) was seen in 28% of patients. The remaining variants (a combination of the 350G mutation with 335T, 145T, or 419G) were significantly associated with cases compared to controls. The 350G + 145T variant was found at much higher incidence in cases in younger women, suggesting that this variant may be associated with aggressive tumor behavior. Interestingly the 350G + 419G combination was found only in controls. There was no significant association between the four genotypes of E7 and any stage of tumor progression or age. CONCLUSIONS: The results indicate that specific mutations in the E6 gene are found in young Indian women with high-grade squamous intraepithelial lesions and invasive cancer, suggesting that these mutations represent more oncogenically active HPV 16. Whether this increased oncogenecity is due to differences in p53 inactivation, ineffective keratinocyte differentiation, and/or altered response to the immune system by these oncogenic E6 mutants remains to be clarified. 相似文献
12.
目的:研究我国宫颈癌高发区新疆维吾尔族妇女宫颈癌与人类乳头状瘤病毒(HPV)感染的关系。方法:对65例新疆维吾尔族妇女的宫颈癌活检组织标本,应用原位杂交法检测HPV6/11、16/18和31/33/35DNA;L1共有序列引物聚合酶链反应(PCR)及E6特异型引物PCR检测其中的58例HPV6、16和18DNA。结果:65例宫颈癌患者中,原位杂交法检测HPVDNA有28例阳性(43.1%);L1PCR和E6PCR检测HPVDNA阳性分别为13例(22.4%)和45例(77.6%)。结论:对宫颈癌标本中的HPVDNA检测,E6特异性引物PCR敏感性最高,L1PCR及原位杂交相对较低。新疆维吾尔族妇女宫颈癌发病与HPV感染有密切关系。 相似文献
13.
de Boer MA Peters LA Aziz MF Siregar B Cornain S Vrede MA Jordanova ES Kolkman-Uljee S Fleuren GJ 《Gynecologic oncology》2004,94(2):488-494
OBJECTIVE: Human papillomavirus type 16 (HPV 16) has several intratypic variants, and some are associated with enhanced oncogenic potential. For risk determination as well as for future vaccine development, knowledge about variants is important. Regarding the geographical distribution of HPV variants and the lack of data from Indonesia and Suriname, we studied the prevalence of HPV 16 variants in cervical cancer in these high incidence countries. Data were compared with The Netherlands, a low-risk country. METHODS: DNA samples from 74 formalin-fixed paraffin-embedded HPV 16-positive cervical carcinomas from Indonesia (Java, N = 22), Suriname (N = 25), and The Netherlands (N = 27) were amplified using primers specific for the E6, E7, and part of the L1 regions. Products were sequenced and analyzed. RESULTS: A specific Javanese variant, with mutations 666A in E7 and 6826T in L1, was found in 73% of the Indonesian samples, 56% having an additional mutation in the E6 open reading frame (ORF; 276G), giving the predicted amino acid change N58S. This Javanese variant was also found in three Surinamese samples, which reflects what could be expected from migration of Javanese people to Surinam. Other non-European variants were identified in Indonesian, Surinamese, and Dutch samples in 14%, 28%, and 19%, respectively. CONCLUSION: The majority of the HPV 16-positive cervical cancers in Indonesia are caused by a specific intratypic variant that was rarely found before in other countries. 相似文献
14.
OBJECTIVE: To determine the integrity of the BRCA1 gene in archival, paraffin-embedded tissues from precancerous lesions of the uterine cervix. STUDY DESIGN: DNA was extracted from histologically documented precancerous cervical lesions (17 cases). Polymerase chain reactions were performed targeting exon 11 of BRCA1 (434-bp), the L1 consensus human papillomavirus (HPV) gene common to > 25 HPV types, as well as the beta-globin gene. The amplified products were analyzed using denaturing gradient gel electrophoresis. RESULTS: Mutation of the BRCA1 exon 11 gene was detected in > 76% of cases with precancerous lesions of the cervix. The mutations were either complete deletions or deletions of one or more nucleotides, leading to frame shifts. There were no significant differences in frequency of BRCA1 mutations among precancerous cervical tissues positive for the HPV L1 consensus gene (n = 9) when compared with HPV-negative tissues. CONCLUSION: The mutated BRCA1 gene was associated with 76% of 17 precancerous lesions of the cervix. The type of cervical intraepithelial neoplasia and the presence or absence of HPV were not related to the mutations. The role of BRCA1 mutation in the genesis of precancerous cervical lesions needs to be explored further. 相似文献
15.
Qiu AD Wu EQ Yu XH Jiang CL Jin YH Wu YG Chen Y Chen Y Shan YM Zhang GN Fan Y Zha X Kong W 《Gynecologic oncology》2007,104(1):77-85
OBJECTIVES: Infection with high-risk human papillomavirus (hr-HPV) is an important factor associated with cervical cancer. The genetic mutation of HPV16 E6 and integration of HPV16 DNA in the cervical carcinoma tissues are considered important genetic changes in cervical lesion progression. But the studies of hr-HPV epidemiology are relatively less in the area of Sichuan, China. Therefore, we investigated the prevalence of 9 high-risk subtypes and analyzed the genetic mutation characteristic of HPV16 E6 and physical state of HPV16 DNA. METHODS: The fragments of L1 and E6 genes were amplified by PCR or nested PCR and then directly sequenced. Further, the multiplex PCR for HPV16 E2 and E6 genes was performed for detection of integration. RESULTS: HPV16, 58 and 18 were prominent, accounting for 78.6%, 20.0% and 9.7%, respectively in 145 isolates. E6 variants revealed that the European (EP) prototype and East Asia (EA) strain were 26 (23.0%) and 34 (30.1%), respectively. Furthermore, there were 14 base substitutions in E6 regions of the study group, of which 12 resulted in amino acid changes and the rest was silent mutation. Significantly, the 240G substitution exactly located the P53 degradation site. Overall, 8 of 114 (7.0%) isolates only contained integrated HPV16 DNA, 43 (37.7%) only contained episomal DNA and 63 (55.3%) contained both integrated and episomal DNA. The proportion of disruption of an intact E2 gene in the patients with cervical cancer is much lower than that in the previous studies. CONCLUSIONS: HPV16, 58 and 18 were mainly prevailing subtypes in patients with cervical cancer from Sichuan areas, China and EP/EA strains were predominant in these areas. Some mutations of E6 gene, which lead to the amino acid changes, may be more potentially carcinogenic and the proportion of disruption of an intact E2 gene is much lower. 相似文献
16.
Polymorphism in the E6 gene of human papillomavirus type 16 in the cervical tissues of Korean women 总被引:3,自引:0,他引:3
S. Kang† Y. T. Jeon† J. W. Kim†‡ N. H. Park† Y. S. Song† S. B. Kang† & H. P. Lee† 《International journal of gynecological cancer》2005,15(1):107-112
The aim of this study was to identify sequence variants in the HPV 16 E6 gene in Korean women and to examine the possible association between these sequence variants and cervical cancer development. We examined the HPV 16 DNA of 215 patients with no cervical disease (NCD) (n = 105) or with cervical neoplasia (n = 110) [cervical intraepithelial neoplasia (CIN), n = 61; invasive cervical carcinoma (ICC), n = 49] using the nested polymerase chain reaction (PCR) and PCR-directed sequencing methods. Fifty-four (NCD, n = 10; CIN, n = 17; ICC, n = 27) of the 215 samples contained HPV 16 E6 DNA, but only two (7.4%) of 27 ICC samples had prototype sequences. The most frequently found variation was D25E (in NCD, n = 8, 80%; in CIN, n = 9, 52.9%; in ICC, n = 23, 85.2%). This is a rare variation in western countries. No significance difference was found between the frequencies of D25E variation in cancerous and non-cancerous lesions. Among the 11 kinds of variants identified, four variants were novel and have been registered with GenBank. This study demonstrates that the D25 variant is the most prevalent E6 genomic variant type in Korean population. However, it was not found to be associated with an increased risk of ICC. 相似文献
17.
Kim HJ Song ES Hwang TS 《European journal of obstetrics, gynecology, and reproductive biology》2001,98(2):213-218
OBJECTIVE: Inactivation of p53, either through mutation or interaction with human papillomavirus (HPV) E6 oncoprotein, is a characteristic feature of cervical carcinoma cell lines that have been previously studied. To elucidate the role of p53 in the carcinogenesis of Korean cervical carcinomas, 27 HPV-positive and 13 HPV-negative cervical carcinomas were studied in order to evaluate the status of the p53 gene. STUDY DESIGN: The HPV status was ascertained by polymerase chain reaction (PCR) amplification using consensus primers designed from the E6 and E7 open reading frames (ORFs). The p53 mutation status was analyzed by direct sequencing of the PCR product in highly conserved exons 5-8. RESULTS: There was no significant difference in the frequency of the p53 mutation between the HPV-positive and negative cases. All three mutations in the HPV-positive cases were associated with intermediate-risk viruses. The average age of the patients with the p53 mutation was 14 years older than that of patients without the p53 mutation. CONCLUSION: p53 mutations are higher in the so called intermediate-risk HPV positive than HPV 16 or 18 positive cervical carcinomas. 相似文献