高危亚型HPV33和HPV52感染与宫颈病变的关系

目的 探讨人乳头瘤病毒(HPV)高危亚型HPV33和HPV52感染与宫颈病变的关系。方法 选取316例于我院进行病理组织活检联合HPVDNA检测的病例,对其进行HPVDNA提取、PCR扩增、导流杂交,其中对194例HPV33和HPV52亚型阳性患者资料进行分析。结果 194例HPV33和HPV52阳性患者中,宫颈良性病变225例,宫颈上皮内瘤变(CIN)为114例和宫颈恶性肿瘤为55例,利用统计学χ~2检验发现在HPV33和HPV52阳性患者中,CIN和宫颈恶性肿瘤的阳性率明显高于宫颈良性病变的阳性率(p<0.05)。结论 HPV33和HPV52阳性患者患宫颈病变的几率增大,高危型HPV33和HPV52是引起宫颈恶性病变的致病基因型。     

宫颈病变合并HPV感染者阴道微生物及Th1/Th2变化

目的 探讨宫颈病变合并HPV感染患者阴道微生物群落及Th1/Th2细胞因子表达的影响。方法 选取我院妇科收治的宫颈病变合并HPV感染患者86例为研究组,选择同期入院未合并HPV感染宫颈病变患者86例为对照组。并依据阴道镜下活组织病理学检查将患者分为宫颈上皮内瘤变Ⅰ级(CINI组)72例、宫颈上皮内瘤变Ⅱ级(CINⅡ组)34例、宫颈上皮内瘤变Ⅲ级(CINⅢ组)36例和宫颈癌(CC组)30例。比较不同组患者阴道内环境,分析微生物群落构成,并对血清白细胞介素-12(IL-12)、干扰素-γ、IL-4、IL-8水平进行比较。结果 随着病变程度的加重,IL-12、IFN-γ水平持续降低,IL-4、IL-8水平持续上升,不同病变程度患者之间Th1/Th2细胞因子水平差异存在显著性(F=17.841、18.473,均P<0.01);研究组厚壁菌门占比(54.49%)低于对照组(74.42%)(χ²=8.171,P=0.004),放线菌门、梭杆菌门占比(分别为23.26%、4.65%)高于对照组(分别为10.47%、0.00%)(分别χ²=4.038、...     

宫颈鳞状细胞癌HPV16/18、p53、p21表达及意义

目的　探讨人乳头状瘤病毒 (HPV) 16型、18型及 p5 3、p2 1基因蛋白的表达情况以及与宫颈癌的关系。 方法　应用免疫组化二步法检测 5 0例宫颈鳞癌、4 0例正常宫颈黏膜中HPV16、HPV18、p5 3、p2 1的表达。肿瘤组分 <6 0岁和≥ 6 0岁 2个年龄组 ,观察HPV感染情况。结果　宫颈鳞癌中HPV16、HPV18、p5 3、p2 1表达分别为 4 8%、2 0 %、5 4 %和 5 0 % ,而正常宫颈黏膜中的表达分别为 10 %、0、0、10 % ,两者经统计学比较差异有显著性 (P <0 0 1) ;<6 0岁组和≥ 6 0岁组HPV16阳性率分别为 84 2 %和 2 5 8% ,年青组明显高于年老组 ,经统计学比较差异有显著性 (P <0 0 1)。结论　 (1)宫颈鳞癌的发生与HPV16、HPV18感染有密切关系 ,提示检测宫颈HPV16、HPV18感染情况对于宫颈鳞癌的随访和早期诊断有着重要的参考价值。 (2 )提示宫颈黏膜在HPV感染后 ,可能在p5 3、p2 1多种癌基因的共同作用导致宫颈鳞癌的发生发展。     

高危型人乳头瘤病毒PCR检测与液基薄层细胞学检测在宫颈病变中的对比性研究

目的:探讨在宫颈病变中液基薄层细胞学检验(TCT)与13种高危型人乳头瘤病毒荧光定量聚合酶链式反应(FQ-PCR)检测的相关性。方法:采用TCT法检验就诊患者的宫颈脱落细胞,用FQ-PCR法检测HPV-DNA,比较两者之间的关系。结果:515例样本中,HPV检测阳性者175例,占全样本的34%。在HPV阳性者中,TCT法检测出非典型鳞状上皮细胞(ASC-US)组61例;上皮内低、中高度病变(CINⅠ、CINⅡ/Ⅲ)组22例;良性反应性改变(重度、萎缩性炎症)组11例;良性反应性改变(中度炎症)组29例;良性反应性改变(轻度炎症)组50例;正常组2例,分别占175例HPV阳性标本的34.8%、12.6%、6.3%、16.6%、28.6%和1.1%。结论:在HPV检测阳性的标本中,其TCT检测结果显示宫颈均有不同程度的病理改变。因此高危型人乳头瘤病毒是导致宫颈病变的主要原因。在妇科的宫颈病变筛查中应将HPV、TCT、宫颈刮片以及阴道镜检查联合起来才更便于早期病变的检出。     

HPV16、58型感染导致宫颈微环境中免疫因子变化及宫颈细胞中病毒整合的初步研究

目的：探讨人乳头状瘤病毒（Hapillomavirus,HPV）16和58型感染导致宫颈局部微环境中免疫因子白介素（Interleukin,IL）-12、IL-4,干扰素（Interferon,IFN）-γ浓度变化及宫颈细胞中HPV16/58病毒DNA整合与宫颈病变进展的关系。方法：收集2012年8月～2013年5月在广西医科大学附属肿瘤医院妇瘤科住院行HPV DNA分型检测,且组织病理结果诊断为宫颈癌患者的宫颈灌洗液共89例及宫颈脱落细胞140例,根据HPV分型结果将89例宫颈灌洗液分组为：①HPV16（＋）58例;②HPV58（＋）31例。应用酶联免疫法（Enzyme linked immunosorbent assay ,ELISA）法检测89例患者宫颈微环境中免疫因子IL-12、IL-4、IFN-γ的浓度;将140例宫颈脱落细胞根据HPV分型结果分组为：①HPV16（＋）106例;②HPV58（＋）34例。采用荧光定量PCR（ qRT-PCR）检测HPV16/58的E2和E6基因,根据E2/E6拷贝数比值判定HPV16/58 DNA的存在状态。结果：①HPV16（＋）组中IL-4浓度明显高于HPV58（＋）组（ P＜0.05）;IL-12、IFN-γ的浓度明显低于HPV58（＋）组（ P＜0.05）。②HPV16 DNA与HPV58 DNA的存在状态有着显著差异（ P＜0.05）,HPV16 DNA整合比率比HPV58 DNA整合比率明显增大。结论：HPV16和58型感染不但可以导致宫颈细胞外局部免疫微环境中的IL-12、IFN-γ的降低和（或） IL-4的升高,还可导致病毒在宫颈细胞内整合,通过宫颈细胞内外变化导致宫颈病变甚至宫颈癌的发生;HPV16较HPV58更容易造成宫颈组织发生癌变。     

妊娠与高危型人乳头瘤病毒感染易感性的相关分析

目的探讨妊娠对高危型人乳头瘤病毒感染率及宫颈病变的影响。方法采用第二代杂交捕获法(HC-Ⅱ)检测60例非孕妇女、60例妊娠妇女不同妊娠时期、产后3月HPV感染率,宫颈脱落细胞薄层液基细胞学检查(TCT)及阴道镜检查。结果妊娠晚期HPV感染率最高(46.7%),妊娠早中期感染率次之(21.7%),产后3个月下降(16.7%),非妊娠期感染率8%,随着妊娠进展,HPV感染率也在不断的增加,各期TCT检查结果比较差异无统计学意义(P>0.05)。结论妊娠对高危型HPV感染的易感性的升高有相关性,应加强孕前、孕期宫颈病变的筛查。     

妇科门诊患者HPV分型检测及结果分析

目的探讨人乳头瘤病毒（human papillomavirus,HPV）的感染在慢性宫颈炎、宫颈上皮内瘤样病变（CIN）及浸润性宫颈癌（ICC）中的表达,旨在提高宫颈上皮内瘤样病变及浸润性宫颈癌的诊断率。方法对就诊的有宫颈疾患的妇女794例,采用导流杂交HPV基因分型技术进行DNA检测。结果 HPV检测阳性113例,阳性率14.23%,其中单一型别HPV感染84例,占总数的74.33%,多型别感染的29例,占总数的25.67%,最常见的HPV基因型为52、16、58、18、53高危型感染率较低危型相比,上升趋势更为明显。结论在宫颈病变筛查中HPV检测可提高细胞学检测的有效性,是早期诊断CINⅢ及ICC的一个重要辅助方法。     

HPV感染和宫颈病变的相关性分析

目的研究北京地区女性HPV感染和宫颈病变关系。方法选择于2014年5月至2018年12月于民航总医院妇产科就诊行阴道镜并取活检的患者,按照宫颈活体病理结果分为无宫颈病变组,LSIL组,HSIL组,宫颈癌组,对其宫颈细胞学、HPV感染和病理结果进行相关性分析。结果共收集2634例患者,无病变组752例,LSIL组1348例,HSIL组497例,宫颈癌组37例。宫颈病变患者共1882例,占71.5%。宫颈鳞状上皮内瘤变及宫颈癌的的高发年龄为30-44岁。HSIL组、LSIL组和宫颈癌组最常见的感染型别均为HPV16型,LSIL组第二三位感染型别依次为HPV 52、HPV58,HSIL组第二三位感染型别依次为HPV 58、HPV52。第四位均为HPV18型;在宫颈癌组中HPV18感染居第二位,HPV52、HPV58、HPV33、HPV68并列位于第四位。结论符合入组条件者发生宫颈病变几率高,应及早行阴道镜检查,重视30-44岁女性的筛查。TCT的阳性结果比阴性结果更有意义,建议TCT与HPV联合筛查减少漏诊率(尤其是30-44岁女性)。除HPV16、18外,建议HPV52、58的感染及时转诊阴道镜检查。     

TCT查验子宫颈涂片中HPV感染的研究

目的评价液基薄层细胞检测技术(TCT)检测宫颈涂片中人乳头状瘤病毒(human papilloma virus,HPV)感染的敏感性与准确性。方法对1030例外阴尖锐湿疣患者的子宫颈涂片,采用TCT检测技术进行细胞病理学诊断,其诊断标准依据The Bethesda System(TBS)分类法。同期行阴道镜指引下的子宫颈活组织检查和聚合酶链反应(PCR)技术检测宫颈拭子中的HPVDNA。结果应用PCR检测1030例宫颈拭子HPVDNA,阳性者37例(35.92%)。宫颈活组织学检查结果为ASCUS57例(5.53%);上皮内病变CIN11例,占总数的1%;占HPV( )百分率为29.73;占57例为非典型麟状细胞阳性的19.3。结论TCT作为一种细胞病理学检测技术,用于诊断宫颈HPV感染或亚临床感染,有临床应用价值。     

基于数学模型的高危HPV E6/E7 mRNA定量分析在宫颈病变筛查中的作用

目的:研究高危人乳头瘤病毒(HPV)E6/E7 mRNA定量分析在宫颈病变筛查中的作用。方法:采用原位杂交技术对440例不同宫颈病变[炎症、低级别上皮内瘤变(CIN)、高级别CIN、浸润性鳞癌]患者行高危HPV E6/E7 mRNA拷贝数进行定量检测,建立数学模型对检测结果进行分析。结果:4组之间HPV E6/E7 mRNA阳性率不全相等,具有统计学差异(P0.005 0);炎症组与其他3组宫颈病变之间高危HPV E6/E7 mRNA阳性率均有统计学差异(P0.008 3)。拷贝数大小与病变程度呈正相关,可知当mRNA小于500时,炎症的可能性比较高;500~10 000时,很可能是CIN(包括低级别和高级别);大于10 000时,很可能是高级别CIN和癌症。结论:高危HPV E6/E7 mRNA拷贝数大小与宫颈病变程度正相关,其定量检测可作为宫颈病变联合筛查的一种有效补充工具。     

Prevalence of human papillomavirus types in cervical lesions from women in rural Western India

Cervical cancer is the most common cancer among women in many areas of India which contributes for a fifth of the global burden of disease. Persistent infection with one of the high-risk human papillomaviruses (HPV) has been established as the cause for cervical cancer and the documentation of the prevalence of HPV types in cervical cancer in different regions of India is useful for a prevention program combining both screening and vaccination. In this study, the HPV type distribution and the frequency of p16(INK4a) immunoexpression have been determined in 125 cases of inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 74 cases of grade 2, 72 cases of grade 3, and 113 cervical cancer cases diagnosed among women from rural Solapur and Osmanabad districts, Maharashtra. The overall prevalence of high-risk HPV was 37.6% in inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 63.5% in grade 2, 97.2% in grade 3 and 92% in cervical cancer cases. HPV 16 and HPV 18 were detected in 80.6% of grade 3 cervical intraepithelial neoplasia and 86.5% of cervical cancer cases. 94.7% of the cervical cancer and 84.4% of the high grade lesions with a strong and full thickness staining for p16(INK4a) were positive for HPV infection; p16(INK4a) immunoexpression increased with worsening grade of cervical intraepithelial neoplasia. The HPV genotyping data showing a high HPV 16 and 18 prevalence in cancer specimens indicate that prophylactic HPV 16/18 vaccination would have a significant impact on the prevention of cervical cancer in India.     

Human papillomavirus is a necessary cause of invasive cervical cancer worldwide

A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalysed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalysed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0·001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99·7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening. Copyright © 1999 John Wiley & Sons, Ltd.     

A pilot study on the distribution of human papillomavirus genotypes and HPV-16 variants in cervical neoplastic lesions from Ecuadorian women

Human papillomaviruses (HPVs) are the cause of cervical intraepithelial neoplasia and invasive carcinomas of the uterine cervix. The distribution of specific HPV genotypes varies greatly across populations and HPV surveys have been performed in different geographical regions in order to apply appropriate vaccine strategies. The aim of this study was to determine the spectrum of HPV genotypes and HPV-16 variants among women with cervical lesions living in Ecuador. A total of 71 cases have been analyzed, including 32 chronic cervicitis, 29 cervical intraepithelial neoplasia grade 1, and 10 cervical intraepithelial neoplasia grade 2-3. HPV sequences were detected by broad spectrum consensus-primer-pairs MY09/MY11 and GP5+/GP6+-based polymerase chain reaction and characterized by nucleotide sequence analysis. Overall, 31 (43.7%) cases were HPV positive with prevalence rates of 37.5%, 44.8%, and 60% in patients with chronic cervicitis, cervical intraepithelial neoplasia grade 1 and cervical intraepithelial neoplasia grade 2-3, respectively. Among the positive cases, the most common genotypes were HPV 16 (64.5%) and HPV 81 (29%) followed by HPV 31, 53, 56, and 58, in descending order of prevalence. Seventeen (85%) HPV-16 isolates were classified as European and three (15%) as African-1 variant on the basis of nucleotide signature present within the MY09/MY11 L1 sequence. The results suggest that HPV 16 has a very high prevalence among women with cervical lesions in Ecuador; therefore, an effective HPV-16 based vaccine should prevent the development of cervical cancer in a large proportion of Ecuadorian women.     

嘉兴地区女性感染人乳头瘤病毒基因亚型分析

目的:了解嘉兴地区妇女宫颈感染人乳头瘤病毒(human papilloma virus,HPV)基因型的分布情况,为嘉兴地区HPV亚型流行病学研究提供依据。方法:取妇女宫颈的脱落细胞,利用导流杂交基因芯片技术,对标本进行HPV分型检测,包括13种高危型、5种低危型和3种中国人群常见亚型。结果:933例标本经HPV分型检测,筛查出398例阳性,感染率42.66%。其中高危型327例,感染率35.05%;低危型272例,感染率29.15%:中国人群常见亚型26例,感染率2.78%。结论:嘉兴地区HPV感染率较高,HPV6、11、16、58是嘉兴地区HPV感染的主要亚型。了解HPV亚型的分布特点对流行病学的调查,降低HPV相关肿瘤的发生和特异性疫苗的研制都有重要意义。     

厦门地区女性人乳头瘤病毒感染状况调查

目的 对厦门地区妇女宫颈人类乳头瘤病毒（human papilloma virus,HPV）亚型进行筛查,以探讨其分布规律.方法 采用凯普医用核酸分子快速杂交仪,对7683名2013年1月-2013年12月到厦门市174医院妇科门诊或病房就诊的女性进行生殖道21种HPV感染基因亚型筛查.结果 7683例样本中,HPV感染者1421例,阳性率18.50％.感染人群主要集中在30～39岁.其中高危型HPV阳性率为16.01％,低危型HPV阳性率为2.49％.单一基因型别者1148例,阳性率为14.94％;双重感染者220例阳性率为2.86％;三重以上感染者53例,阳性率为0.70％;HPV感染阳性率居前6位的基因型分别为HPV-52（3.64％）、HPV-16 （3.33％）、HPV-58（2.98％）、HPV-53（2.16％）、HPV-CP8304（1.91％）和HPV-18（1.09％）.结论 厦门地区妇女HPV感染率高,且以高危型单一基因亚型感染为主;感染基因型别主要以HPV-52、16、58、53、CP8304和18为主,具有一定的地域差异性;52及58型感染率高,对于疫苗的研制和开发有参考意义.     

Typing of human papillomavirus in women with cervical lesions: Prevalence and distribution of different genotypes

Human papillomavirus (HPV) are distributed widely and persistent infection with high‐risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim of this study was to evaluate the distribution of different HR‐HPV genotypes in 199 women with cervical pre‐invasive lesions undergoing conservative treatment. A Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in cervical samples. It was observed that the most prevalent HPV genotypes were HPV 16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the patients. Stratifying the different HPV genotypes according to the severity of the cervical lesion, a strong association between the increasing severity of the histological diagnosis and the detection of more carcinogenic HR‐HPV type was found, and in all but one cervical intraepithelial neoplasia of grade 3 the presence of at least one HR‐HPV could be detected, with more than 70% of cervical intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple infections, comprising between 2 and 6 HPV types, were found in 43% of patients; however, the presence of more than 1 HR‐HPV type was not associated with an increased risk of high grade lesions. In conclusion, this data show that HPV 16, 51, 31, 52, and 18 were the prevalent types found in patients with cervical lesion undergoing conservative treatment, with a high prevalence of HPV 16 in cervical intraepithelial neoplasia of grade 3 patients. No association between multiple infection and severity of the lesion could be found. J. Med. Virol. 81:271–277, 2009. © 2008 Wiley‐Liss, Inc.     

Distribution of HPV genotypes in Shanghai women

Objective: To study the Distribution of HPV genotypes in Shanghai women. Design: Cohort study. Setting: Shanghai First Maternity and Infant Hospital affiliated with Tongji University. Population: Patients those attended in the cervical disease diagnosis and treatment center of Shanghai First Maternity and Infant Hospital between January 2011 and December 2014. Methods: HPV GenoArray test kit (HybriBio Ltd) was used to perform HPV genotyping and was also used in DNA amplification and HybriBio’s proprietary flow-through hybridization technique. Results: In this study, total patients analyzed were 4585. Among 4585 sample the HPV positive patients were 1460 i.e. 31.84% in total. On the basis of pathological report normal were 1358, with inflammation 2441, with low grade lesion were 399, high grade lesion were 353, CIN were 19 and cervical carcinoma were 15. Among normal HPV positive were 215 (15.8%), among inflammation HPV positive were 735 (30.11%). HPV positive in low grade lesion were 353 i.e. 59.77%. In high grade lesion 211 were HPV positive among 272 (68.17%). The percentage of HPV positive was 73.68% i.e. 14 out of 19 patient in cervical carcinoma in situ. 13 patient out of 15 i.e. 86.67% of Cervical carcinoma were HPV positive. Among all percentage of HPV positive was high among cervical carcinoma then cervical carcinoma in situ then high grade lesion in decreasing fashion to low grade lesion and in normal. Highest prevalence i.e. 22.67% is of HPV 52 subtype and HPV 16 has second highest prevalence with 17.67% among HPV positive cases. Sensitivity of TCT detection is 71.6%. Specificity of TCT detection is 79.6%. Sensitivity of HPV-DNA detection is 65.2%. Specificity of HPV-DNA detection is 78.2%. Conclusion: HPV is one of major health concern in shanghai having high prevalence rate in comparison to other part of china and other part of world. This has implications for the future cervical cancer burden and the priority to be given to prevent cervical cancer in Shanghai, especially, given the promising efficacy of prophylactic vaccines against HPV52, 16 and 58. This study also shows high sensitivity and specificity of TCT and HPV-DNA detection.     

太原地区404例女性HPV感染状况及基因分型统计分析

目的探讨太原地区女性人乳头瘤病毒(HPV)感染情况以及基因分型分布及特点。方法采用人乳头瘤病毒基因分型检测试剂盒(PCR技术及导流杂交技术)对太原地区404例女性进行21种HPV亚型分析。结果 404例检测者共检测到HPV阳性患者213例,阳性率为52.7%。21种HPV亚型(除HPV 42、43型外)均有检出,其中检出率较高的高危型有HPV 16(34.4%),HPV 58(13.4%),HPV 53(8.7%);检出率最高的低危型是HPV 6(2.2%)。阳性检出者中单一亚型感染占59.6%,多种亚型感染占40.4%;在多重感染中,伴随着合并感染的亚型数增加,比例逐渐下降。结论利用PCR技术和杂交技术检测女性HPV感染情况,对宫颈癌的早期诊断、预防及疗效观察具有重要的应用价值。     

子宫颈癌预防研究的里程碑

子宫颈癌是常见的妇科恶性肿瘤,其发病率在女性恶性肿瘤中居第二位。据2002年数据统计,全球估计有49万的子宫颈癌新发病例,27万多妇女死于该病。半个多世纪以来,人类试图努力用巴氏涂片来消灭子宫颈癌。子宫颈癌的病因学研究在80年代取得的显著进展,明确了人乳头瘤病毒与子宫颈癌病因学联系。而HPV预防性疫苗研制的成功则是子宫颈癌预防研究的里程碑。