300例妇科宫颈病变患者石蜡切片HPV基因分型结果分析

探讨女性生殖道感染人乳头瘤病毒(HPV)和不同宫颈病变的关系及HPV检测在宫颈癌防治方面的应用价值.对阴道镜活检病理诊断的300例不同的宫颈病变患者进行HPV-DNA检测(同时检测5种低危型和18种高危型HPV亚型).结果显示,慢性宫颈炎组HPV阳性87例,阴性48例,阳性率64.5%;子宫颈上皮内瘤变(CIN)组(C...     

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。     

P16和FHIT基因联合高危HPV检测在宫颈癌诊断中的研究

目的探讨P16、脆性组氨酸三联体（FHIT）基因启动子异常甲基化及高危HPVDNA与宫颈病变恶性程度的相关性及三者联合检测的的临床意义。方法采用巢式甲基化特异性PCR方法检测26例宫颈癌及35例宫颈上皮内瘤变患者（CIN）P16、FHIT的甲基化状态，同时测定其高危HPVDNA并与43例无上皮内瘤变患者作对照，分析三者联合检测的临床诊断价值。结果宫颈癌患者P16、FHIT基因启动子异常甲基化及高危HPV阳性率分别为23．7％、65．4％、88．4％。CIN患者P16、FHIT基因启动子异常甲基化及高危HPV阳性率分别为5．7％、11．4％、42．8％。健康对照者标本中P16、FHIT基因无异常甲基化。高危HPV阳性率为13．9％。结论P16、FHIT基因启动子异常甲基化及高危HPV与宫颈病变恶性程度相关，联合检测P16、FHIT启动子异常甲基化及高危HPV可提高宫颈癌诊断的敏感性和特异性，对于宫颈癌的早期诊断具有重要意义。     

宫颈上皮内瘤样病变患者高危型HPV感染基因分型分析

目的了解宫颈上皮内瘤变患者的高危型HPV的感染及其分型和不同程度宫颈病变的主要感染型别情况。方法应用型特异PCR检测宫颈癌前病变的患者的主要高危型HPV-16、18、33、58的感染及其分型情况的相关性研究。结果在本研究宫颈上皮内瘤变患者98例中,4种高危型HPV的总阳性例数为73例,HPV总的感染率为74.5%,存在多重感染。其中HPV-16、18、33、58的总感染率分别为53.1%、38.7%、17.3%和30.6%。CIN的Ⅰ/Ⅱ/Ⅲ3组患者的4种高危型HPV的感染率分别为42.9%、61.1%和93.2%。结论主要高危型HPV在宫颈上皮内瘤变患者中感染的主要型别依次为HPV16、HPV18、HPV58、HPV33,主要为HPV16和HPV18型;不同程度CIN的高危型HPV的总感染率不同,随病变程度的加重而增加。     

北京市北苑地区女性HPV感染现状及基因型分布研究

目的 调查我院辖区范围内即北京市北苑地区成年女性人乳头状瘤病毒(HPV)感染现状及亚型分布情况.方法 采用核酸分子快速导流杂交基因芯片分型技术对本院辖区范围内(北苑地区)来我院妇科门诊就诊的14582例女性患者采集宫颈脱落细胞标本进行HPV及21种亚型检测.结果 ①HPV感染阳性检出2419例,感染阳性率16.59％(2419/14582),在HPV感染阳性人群中,以单一高危型HPV感染为主,单一感染HPV阳性1951例,占HPV阳性感染人群80.65％(1951/2419);多重感染以二重感染为主,多重感染HPV阳性468例,二重感染HPV阳性361例,占HPV阳性感染人群14.92％(361/2419),以高危型感染以为主.②各HPV基因亚型检出总和为3035项次,高危型HPV感染占91.73％(2784/3035),排在前五位由高到低依次是HPV16(17.36％,527/3035)、HPV52(11.89％,361/3035)、HPV58(11.80％,358/3035)、HPV53(8.27％,251/3035)、CP8304(7.05％,214/3035),以HPV16型为主;低危型HPV感染占8.27％(251/3035),由高到低依次是HPVl1 (3.95％,120/3035)、HPV6(3.57％,108/3035)、HPV44(0.43％,13/3035)、HPV42 (0.16％,5/3035)、HPV43 (0.16％,5/3035),以HPV11为主.③按年龄段划分,≤20岁年龄组阳性率最高,阳性率31.30％ (36/115);其次是≥61岁年龄组,阳性率21.05％ (64/304).结论 本院辖区范围内(北苑地区)成年女性HPV感染阳性率16.59 ％(2419/14582),以单一高危型HPV感染为主,高危型HPV16、HPV52、HPV58、HPV53、CP8304是本院辖区范围内成年女性HPV感染的主要亚型.     

134例宫颈上皮内瘤变患者HPV分型检测结果分析

目的探讨宫颈上皮内瘤变(CIN)中不同类型人乳头瘤病毒(HPV)的感染及分型情况。方法回顾性研究北京军区总医院妇科门诊134例已经确诊的CIN患者,采用凯普的核酸分子快速导流杂交基因芯片技术对HPV进行分型。结果 1.各级别CIN以HPV高危亚型单一或者多重感染为主;2.在HPV阳性的101例患者中,单一感染者73例(72.28%),双重感染者24例(23.76%),三重感染者3例(2.97%),四重感染者1例(0.99%);3.HPV-16、58感染率最高,分别为30.83%,24.06%。结论 HPV感染以高危型和多重感染为主;随CIN级别的增高,HPV阳性率也是增高的;HPV-16亚型的感染率最高。     

人乳头瘤病毒检测在宫颈病变中的应用价值

目的了解宫颈细胞学异常患者中人乳头瘤“毒（HPV）的感染状况,评估HPV检测在宫颈病变筛查中的价值。方法随机选取宫颈薄层液基细胞学检测异常的101例患者进行了HPV检测,同时行组织病理学检查。结果（1）101例宫颈细胞学异常患者中,细胞学为ASCUS、LSIL、HSIL、鳞状细胞癌时高危型HPV阳性率分别为84．2％、88．6％、100．0％和2／2;（2）10l例细胞学异常患者中20例为CINI,81例为CINⅡ及以上级别,高危型HPV阳性率存CINI、CINⅡ及以上级别分别为60％、97．5％;（3）ASCUS组中,高危型HPV阳性患者中CINⅡ及以上病变的发生率为87．5％,HPV阴性患者中CINⅡ及以上病变的发生率为16．7％;（4）高危型HPV型别分布由高到低分别为HPVl6型39．6％（40／101）,HPV58型17．8％（18／101）,HPV52型16．8％（17／101）,HPVl8型9．9％（10／101）以及HPV33型9．9％（10／101）。结论高危型HPV感染率与宫颈病变级别呈正相关;HPV检测可作为ASCUS患者的有效分流手段。宫颈病变患者中高危型HPV感染以16、58、52、18、33型为主。     

宫颈癌及其前期病变HPV感染与基因型分布

目的了解宫颈癌及宫颈上皮内瘤变CIN患者的HPV的感染和其基因分型及主要感染型别情况。方法应用型特异PCR检测宫颈癌及其前病变的患者的HPV感染及其主要基因分型情况的分析。结果在本研究宫颈癌及宫颈上皮内瘤变患者中,宫颈癌的HPV感染率为91．0％,CINⅠ／Ⅱ／Ⅲ的HPV感染率为73．3％,主要高危型HPV基因型别依次为HPV16、HPV18、HPV58、HPV33。结论在宫颈上皮内瘤变患者中感染主要高危型HPV基因型别依次为HPV16、HPV18、HPV58、HPV33、HPV16在宫颈癌和CIN中的构成比随着宫颈病变的增加而明显增加。     

高危HPV感染与宫颈病变的相关性分析

目的研究高危型人乳头瘤病毒(high-risk human papilloma virus,HR-HPV)感染与宫颈病变的相关性,为患者早期防治以及临床及时诊断提供有效依据。方法从2018年4月-2019年3月本院就诊患者中共检出946例高危型HPV感染患者,回顾性分析其中121例患者 HR-HPV与宫颈病变的关系。结果 121例研究对象中,分别有高危HPV16、高危HPV18、其他13种高危型HPV单一感染或多重感染,其中感染所占比例依次为:19.01%、8.26%和72.73%;宫颈CIN病变的发生与感染HPV的基因型有关,其中HPV16型、HPV18型感染导致宫颈CIN病变的发生率与其他13种HPV型别比较,差异有统计学意义(P0.05);宫颈活检结果中慢性宫颈炎所占比例为75.21%(91/121),鳞状上皮乳头瘤样增生占15.70%(19/121),CIN Ⅰ占4.96%(6/121),CIN Ⅱ 0.83%(1/121),CIN Ⅲ占3.31%(4/121)。结论 HR-HPV感染与宫颈病变关系密切,应加强对女性 HPV 感染的检测和筛查。     

HIV合并HPV阳性标本中HPV的型别检测

目的探讨深圳地区人类免疫缺陷病毒（HIV）阳性人群中人乳头瘤病毒（HPV）感染分型情况,为HIV阳性人群中HPV感染的防治提供依据。方法运用荧光PCR方法和反向斑点杂交技术对HPV阳性患者进行HPV分型检测。结果在HIV感染者中。利用反向点杂交分型方法对40例HPV阳性标本进行HPV基因分型。其中单型感染有18例（45．0％）,混合感染有19例（47．5％）,共检出16种HPV型别,其中包括11种高危型（16、18、31、33、35、45、52、56、58、68、73型）和5种低危型（6、11、42、44、54型）。在16种型别中,感染率最高的为16型（25．0％）,其次为52型（17．5％）、58型（15．0％）。结论感染HIV人群中生殖器部位HPV的感染率较高,在HIV阳性人群中检出性病相关的高危HPV16／52／58亚型．对HIV阳性人群中HPV感染的防治有重要指导意义。     

Distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia and invasive cervical cancer in Canada

Infection with high‐risk human papillomavirus (HPV) causes cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC). The distribution of HPV types in cervical diseases has been previously described in small studies for Canadian women. The prevalence of 36 HPV genotypes in 873 women with CIN and 252 women with ICC was assessed on cervical exfoliated cells analyzed with the Linear Array (Roche Molecular System). HPV16 was the most common genotype in CIN and ICC. The seven most frequent genotypes in order of decreasing frequency were HPV16, 51, 52, 31, 39, 18, and 56 in women with CIN1, HPV16, 52, 31, 18, 51, 39, and 33 in women with CIN2, HPV16, 31, 18, 52, 39, 33, and 58 in women with CIN3, and HPV16, 18, 45, 33, 31, 39, and 53 in women with ICC. HPV18 was detected more frequently in adenocarcinoma than squamous cell carcinoma (P = 0.013). Adjustment for multiple type infections resulted in a lower percentage attribution in CIN of HPV types other than 16 or 18. The proportion of samples containing at least one oncogenic type was greater in CIN2 (98.4%) or CIN3 (100%) than in CIN1 (80.1%; P < 0.001 for each comparison). Multiple type infections were demonstrated in 51 (20.2%) of 252 ICC in contrast to 146 (61.3%) of 238 women with CIN3 (P < 0.001). Adjusting for multiple HPV types, HPV16 accounted for 52.1% and HPV18 for 18.1% of ICCs, for a total of 70.2%. Current HPV vaccines should protect against HPV types responsible for 70% of ICCs in Canadian women. J. Med. Virol. 83:1034–1041, 2011. © 2011 Wiley‐Liss, Inc.     

Transition of high-grade cervical intraepithelial neoplasia to micro-invasive carcinoma is characterized by integration of HPV 16/18 and numerical chromosome abnormalities

Cervical intraepithelial neoplasia (CIN I, II, and III) and cases of CIN III associated with micro-invasive cervical carcinoma (CIN III & mCA) were analysed for evidence of episomal or integrated human papillomavirus (HPV) 16/18 DNA by fluorescence in situ hybridization (FISH). In parallel, numerical aberrations of chromosomes 1, 17, and X were determined in these lesions as indicators of genomic instability. HPV 16/18 DNA was present in 2 of 12 CIN I, 19 of 23 CIN II/III, and 10 of 12 CIN III & mCA. None of the CIN I and only two of the 19 HPV 16/18-positive solitary CIN II/III showed an integrated HPV pattern. However, all ten cases of HPV-positive CIN III & mCA showed this pattern. Transition of CIN II/III to CIN III & mCA therefore correlates strongly with viral integration (p<0.001). Chromosomal aberrations were detected in 23 of 31 HPV 16/18-positive lesions (14 solitary CIN I-III and nine CIN III & mCA) and 5 of 16 HPV-negative lesions. Nine of 21 HPV 16/18-positive solitary CIN I-III showed tetrasomy for all chromosomes tested, while trisomies for a single chromosome were seen in a further five of these HPV-positive lesions. In eight of ten HPV-positive CIN III & mCA, predominantly aneusomies and/or polysomies were detected. A significant correlation (p<0.02) was found between the chromosome copy number and the physical status of HPV, indicating that in its episomal form HPV induces genomic changes such as tetrasomies and single trisomies, while HPV integration correlates with aneusomies and polysomies, predominantly detected in CIN III & mCA. These data indicate that integration of HPV 16/18 DNA is a pivotal step in the transition of CIN to micro-invasive carcinoma.     

Human papillomavirus infection and invasive cervical neoplasia: a study of prevalence and morphology

The prevalence of human papillomavirus (HPV) DNA sequences in 45 cervical cancer biopsies was examined with the hot-start polymerase chain reaction (PCR), employing HPV consensus primers from the L1 region. The cases comprised 38 squamous cell carcinomas, three adenosquamous carcinomas, and four adenocarcinomas. PCR products were typed with single-strand conformation polymorphism (SSCP) and the HPV types detected were correlated with tumour type. Forty-three biopsies were HPV-positive, HPV16 being the most prevalent type. HPV18/33/45/58 were also detected, but no low-risk or multiple types. Keratinizing squamous cell carcinoma was invariably associated with HPV16 and adenosquamous carcinoma and adenocarcinoma with HPVs 18/45. Non-keratinizing squamous cell carcinomas harboured all five detected types. Our data corroborate the view that malignant cervical tumours are almost invariably associated with high-risk HPV and that certain malignant cervical tumour phenotypes correlate with specific HPV types. © 1997 John Wiley & Sons, Ltd.     

Prevalence and distribution of cervical human papillomavirus genotypes in women with cytological results from Sichuan province,China

The epidemiologic characteristics of human papillomavirus (HPV) genotypes vary by age, ethnicity, and geographic location, and the available data on HPV epidemiological characteristics with cytology results in Sichuan province are limited. Our research was conducted from June 2016 to July 2017. A total of 10 953 women getting HPV testing were enrolled. Liquid-based cytological and histological results were collected. The overall HPV infection rate was 24.1% in Sichuan province. The prevalence of high-risk HPV (hrHPV) was 19.9%. For hrHPV genotypes, HPV52 (15.5%) was the most prevalent genotype, followed by HPV16 (13.8%), HPV58 (13.3%), HPV51 (8.6%), HPV39 (8.1%), and HPV68 (7.8%). Among all HPV-positive women with a cytology or histology result, HPV16-positive women have the highest cervical intraepithelial neoplasia 1 (CIN1)+ prevalence (11.1%), followed by HPV18 and HPV33; HPV16-positive women also have the highest CIN2+ prevalence (9.3%), followed by HPV58 and HPV18. To date, this is the largest study done in the Sichuan province for HPV prevalence and subtype distribution with normal and abnormal cytological results. The age-specific prevalence in patients at gynecology clinics and other clinics is different. Besides, patients at the same age also have a different hrHPV prevalence and lrHPV prevalence. Our result revealed that in every 10 HPV16-positive women, there is approximately one women with CIN2, CIN3, or cervical cancer. A higher oncogenic potential of HPV58 than that of HPV52 was observed.     

Real-time Taqman PCR targeting 14 human papilloma virus types

BACKGROUND: Subtyping of human papilloma virus (HPV) may enhance the precision of vaginal cytological assessments and will be important for investigating the effect of the recently introduced vaccine against types 16 and 18. OBJECTIVES AND STUDY DESIGN: To evaluate an in-house real-time PCR targeting HPV types 16-18-31-33-35-39-45-51-52-56-58-59-6-11, by analysing 107 liquid-based cytology specimens representing various degrees of dysplasia. RESULTS: In all, 71 samples were HPV positive, with multiple types present in 37 (52%). Comparison with Roche Linear Array on a subset of 24 of these 71 samples showed a good agreement. One or several types were detected in 17/17 (100%) samples with cervical intraepithelial neoplasia grade 2-3 (CIN 2-3), 16/19 (84%) with CIN 1, 32/43 (74%) with Atypical Squamous Cells of Undetermined Significance (ASCUS), and in 6/28 (21%) with benign cytology. Estimates of mean viral load were lower in CIN 1-3 than in ASCUS ( approximately 4000 vs. approximately 25,000 copies/1000 cells), and clearly lower in samples with benign cytology ( approximately 50 copies/1000 cells). CONCLUSION: The HPV rates in groups with different degrees of dysplasia agrees with previous reports and support a strong link between types 16/18 and severe dysplasia. The high rate of multiple type infection might influence the outcome of HPV vaccination. The possible importance of viral load should be further studied.     

Detection of human papillomavirus DNA sequences by in situ DNA-DNA hybridisation in cervical intraepithelial neoplasia and invasive carcinoma: a retrospective study.

Human papillomavirus (HPV) infection of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma was investigated using in situ DNA-DNA hybridisation on histological sections of formalin fixed, paraffin embedded tissue to assess the technique's sensitivity and to assess retrospectively the association between HPV16 and invasive cervical carcinoma. HPV DNA was detected in 16 of 33 biopsy specimens of CIN. Cells containing viral DNA were more numerous than those positive for viral structural proteins. HPV DNA was also present in less differentiated cells deeper in the epithelium. The detection rate in CIN was lower than that reported for other hybridisation techniques such as Southern blotting. In a retrospective study of biopsy specimens of invasive squamous carcinoma of the cervix HPV16 DNA, the virus most commonly associated with cervical malignant disease, was found in 20 of 25 cases, including those dating from as far back as 1932. The level of sensitivity was similar to that reported for other hybridisation techniques. DNA positive cells were focally distributed in the invasive tumours, and most tumour cells were negative for viral DNA, a result consistent with the low copy number found in malignant cells. It is concluded that HPV16 is not a new virus but that its prevalence is a result of changes in sexual behaviour and that in situ hybridisation is useful in the localisation of HPV DNA replication in CIN and invasive carcinoma.     

The prevalence of VAIN,CIN, and related HPV genotypes in Japanese women with abnormal cytology

Vaginal intraepithelial neoplasia (VAIN) is often found by chance. We investigated the prevalence of VAIN and related human papillomavirus (HPV) types in comparison with cervical intraepithelial neoplasia (CIN). This study enrolled 648 women who were referred to the outpatient clinic of Kanazawa Medical University Hospital for abnormal cytology from January 2009 to January 2019. HPV genotypes were determined using Genosearch-31 + 4, which can detect 35 different HPV types. Colposcopy was performed at the first visit by an experienced gynecological oncologist. Among 611 subjects with squamous cell lesions, 107 (17.5%) VAIN cases were identified, and 67 (11.0%) women had both VAIN and CIN. Ultimately, 72 VAIN1, 15 VAIN2/3, 203 CIN1, 249 CIN2/3, 32 cervical squamous cell carcinomas (SCC), and one vaginal SCC (Vag-SCC) were identified. The prevalences of VAIN1, VAIN2/3, and Vag-SCC were 35.5%, 6.0%, and 3.1% of equivalent cervical lesions, respectively. The VAIN patients were older than the CIN patients (P = .002). About half of the VAIN cases were diagnosed during the follow-up. Multiple HPV infections were found in 42.9% of the VAIN and CIN patients. HPV52, 16, 51, 53, and 56 were the most common types in VAIN, whereas HPV16, 52, 58, 51, and 31 predominated in CIN. HPV18 was rare in VAIN, HPV58 was more common in CIN than in VAIN, and HPV53 and HPV73 were more common in VAIN. In conclusion, VAIN1 was identified more frequently than we expected. Various HPV types were identified in the vagina, which is likely a reservoir for HPV.     

The relationship between the cervical and anal HPV infection in women with cervical intraepithelial neoplasia

BackgroundMore than 90% of cases of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) is established as possible risk factor.ObjectivesTo demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer.Study designA total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy-confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Cobas and Lynear array HPV test.ResultsCervical, anal, and concurrent cervical and anal HPV infections were detected in 82.6%, 48.3% and 42.4% of women in the study group, and in 28.0%, 26.0% and 8.0% of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections of the cervix and anus occurred 5.3-fold more often in the study group than in the control group. Any contact with the anus was the only significant risk factor for development of concurrent HPV infection.ConclusionsConcurrent anal and cervical HR HPV infection was found in nearly half of women with CIN 2+. The dominant genotype found in both anatomical locations was HPV 16. Any frequency and any type of contact with the anus were shown as the most important risk factor for concurrent HPV infection.     

Outcome in mild and moderate cervical dysplasias related to the presence of specific human papillomavirus types

In situ hybridization with biotinylated DNA viral probes (ISH-B) for human papillomavirus (HPV) types 6/11, 16, 18, 31, and 33 was used to study the outcome in 32 cases of mild and 21 cases of moderate cervical dysplasia with koilocytotic change that were followed for an average of 27 mo. The rates of regression, persistence, and progression for cervical intraepithelial neoplasia (CIN) I and CIN II were 50%, 41%, and 9%, and 43%, 48%, and 9%, respectively. While progression of HPV 16 CIN I and II lesions was observed, regression occurred in 80% (four of five) and 43% (three of seven) of CIN I and II HPV 16-positive lesions, respectively. Regression was also seen in lesions that contained HPV 31 or HPV 33. All of the HPV 18 lesions persisted. The findings are compared with those of previous studies. Since some of the assumed more aggressive viral types can regress when followed by cytologic and biopsy examinations, caution must be exercised when attempting to predict the clinical outcome based solely on the specific viral type present in a given CIN lesion.