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。     

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。     

人类乳头状瘤病毒分型检测在宫颈癌筛查中的临床研究

目的 探讨人类乳头状瘤病毒（human papillomavirus,HPV）基因分型检测在宫颈病变诊断中的临床应用价值.方法 选取2010年1月至2012年12月在北京大学第一医院妇产科就诊的1715例患者作为研究对象,所有患者均行宫颈脱落细胞学检查、HPV分型检测及阴道镜检查下行多点活检,并最终经组织病理学检查诊断为宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）.分析HPV分型检查在宫颈癌筛查诊断中临床应用价值.结果 1715例CIN患者HPV检出率排名前五位的依次是HPV16、58、52、33、31;CIN2＋（包括CIN2/CIN3/原位腺癌/宫颈癌,以下简称CIN2＋）患者中前五位依次是HPVI6、58、33、52、31;其中CIN2＋中细胞学未见上皮内病变细胞和恶性细胞（negative for intraepithelial lesion or malignancy,NILM）患者中,Logistic回归分析结果显示HPV16、33和18型阳性致CIN2＋风险性较大,回归系数OR分别为5.031（P=0.000）、2.375 （P=0.000）和1.598（P =0.027）.宫颈脱落细胞学为非典型鳞状上皮细胞（atypical squamous cells of undetermined significance,ASCUS）,伴随HPV16、58型阳性,发生CIN2＋风险性较大,回归系数OR分别为5.139（P=0.000）和2.096（P=0.025）.宫颈脱落细胞学为低度鳞状上皮内病变（low squamous intraepithelial lesion,LSIL）,伴随HPV16、33、52型CIN2＋风险性较大,回归系数OR分别为5.774（P =0.000）、3.368（P =0.000）和1.747（P=0.034）.结论 HPV分型检测在宫颈癌筛查中具有重要作用,是指导细胞学阴性、ASCUS和LSIL患者临床处理时的重要参考指标,尤其是当HPV16型阳性时.     

实时荧光定量PCR法检测人乳头状瘤病毒的实验研究

目的 通过研究病变宫颈中人乳头状瘤病毒(HPV)16/18型的表达,探讨HPV16/18型病毒感染与宫颈病变发生发展之间的关系.方法 结合病理切片诊断,以免疫组化作对照.运用实时荧光定量PCR技术检测病变宫颈中HPV16/18型DNA拷贝数,以及HPV16/18型E7基因mRNA表达量.结果 慢性宫颈炎患者中HPV16/18型感染率低(7.4%).宫颈管上皮内瘤样变(CIN)组HPV16型感染率较高为69.6%,宫颈癌患者巾为72.7%.HPV16型DNA的拷贝数在宫颈上皮内瘤样变患者中与病理分级没有明显的相关性.但在宫颈癌患者中,病毒DNA的拷贝数明显升高,二者差异明显.CIN轻度(I)、中度(Ⅱ)、高度(Ⅲ)组和宫颈癌患者中,HPV16 E7基冈的表达率分别为0、37.5%、42.9%、63.6%.统计学分析表明,HPV16 E7 mRNA的拷贝数与病情呈明显的正相关性.结论 感染者中主要以HPV16型为主,HPV18型较少.宫颈癌患者中HPV16 DNA拷贝数明显高于CIN Ⅱ、Ⅲ组,HPV16型E7 mRNA在宫颈癌中表达率及表达量明显增加并与宫颈癌变呈正相关.实时荧光定量PCR适合临床宫颈病变病毒的筛查与检测.     

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。     

不同年龄组宫颈病变21型别人乳头状瘤病毒DNA的观察分析

目的探讨不同年龄组不同类型宫颈病变中21型别HPV DNA的检测及意义。方法应用HybriM ax基因芯片导流杂交法检测71例宫颈病变中HPV DNA,年龄自20-64岁。宫颈病变分为鳞状上皮增生空变、尖锐湿疣、低级别C IN及高级别C IN。HPV DNA 21种型别被检测,其中高危15型,低危6型。结果71例宫颈病变中50例HPV DNA阳性（69%）;按年龄分类,HPV DNA检出的频次以20-25岁（81%）最高,31-40岁最低（56%）（P=0.286）。其中高危型及高低危混合型HPV感染62%,低危型感染7%。HPV感染率在鳞状上皮增生伴空泡变性中33%,尖锐湿疣92%,低级别C IN中89%,高级别C IN中100%（χ2=26.874,P=0.001）;其中高级别C IN中均为高危型HPV基因型阳性,阳性频次基因型依次为16、33、52、18;低度C IN病变HPV基因型依次为16、31、18、52、33、6、11等。单一型别感染率65%,多重型别感染率34%。结论HPV感染可发生于各年龄组,大多数HPV感染不引起宫颈病变,可自行清除。HPV感染与病变的类型明显相关,随着病变的加重,HPV阳性率增高,高危型HPV阳性率亦随之增高。宫颈高级别C IN HPV感染型别依次为16、33、52、18等;低级别依次为16、31、18、52等。     

应用表面等离子共振生物传感器分型检测HPV及其应用评价

目的评价表面等离子共振(SPR)生物传感器分型检测女性生殖道人类乳头瘤病毒(HPV)的临床应用价值。方法采集女性宫颈脱落细胞504例,按病理学结果分为炎症组、宫颈上皮内瘤变(CIN)Ⅰ组、CINⅠ-Ⅱ组、CINⅡ组、CINⅢ组、宫颈癌组。应用SPR生物传感器对各组进行检测,一次性分型检测16种HPV高危型和8种低危型,同时采用克隆测序作平行对照,结合病理诊断结果,对SPR生物传感器进行应用评价。结果SPR生物传感器和克隆测序结果的一致率为0.994,Kappa指数为0.987,(P=0.0000.05)。SPR生物传感器测得各病理组别HPV阳性率、高危型阳性率及多重感染率依次为总体(64.7%、62.1%、15.5%),炎症(41.9%、36.6%、11.8%),CINⅠ(44.6%、41.2%、13.5%),CINⅠ-Ⅱ(51.9%、48.1%、11.1%),CINⅡ(74.2%、74.2%、9.7%),CINⅢ(94.3%、93.5%、23.6%)及宫颈癌组(98.2%、98.2%、16.4%)。24种HPV基因型检出21种,阳性率依次为:16、58、33、52、66、11、18、53、6、31、45、39、81、59、70、68、51、54、56、35、40。SPR生物传感器检测HPV DNA诊断CIN III和宫颈癌的灵敏度为95.5%、特异度为52.1%、阳性预测值为52.1%、阴性预测值为95.5%。结论随宫颈病变严重程度的增高,HPV感染率和高危型感染率呈升高趋势,多重感染率无明显升高趋势;SPR生物传感器检测HPV DNA与克隆测序一致性良好,可以实现HPV分型检测,其诊断CINⅢ和宫颈癌具有较高的灵敏度和阴性预测值,在宫颈病变的临床诊断和流行病学调查中具有重要意义。     

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。     

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。     

宫颈瘤变程度与其相对应的HPV基因型分布规律的研究

目的研究不同级别宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）与人乳头瘤病毒（Human papil-lomavirus,HPV）基因型分布之间的关系。方法收集321例经组织病理学诊断确定为CIN2及以上（CIN2＋）病人的宫颈分泌物标本,其中CIN2 67例,CIN3/ACIS 247例,浸润性宫颈癌7例。采用深圳亚能生物技术有限公司的人乳头瘤病毒（HPV）基因分型检测试剂盒对所选标本进行HPV检测及基因分型。结果在所有321例标本中,HPV阳性300例,阳性率93.5%,两型及两型以上感染138例,占比43.0%。HPV16最常见,检出率为41.1%（132/321）,其次为HPV31,33,52,18和51。HPV16和33的单型感染在CIN3＋中比CIN2更常见,具有统计学差异（P〈0.05）。在包含有HPV16或HPV33的多型感染中,含有HPV16或HPV33的多型感染在CIN3＋中比CIN2更常见,具有统计学意义（P〈0.05）。结论 HPV16和HPV33比其他型别HPV具有更强的潜在致癌性。     

聚合酶链反应酶谱分型检测宫颈癌中人乳头瘤病毒 …

目的 探讨人乳头瘤病毒（ＨＰＶ）和单纯疱疹病毒（ＨＳＶ）等对宫颈癌的病因学作用。方法 应用聚合酶链反应（ＰＣＲ）－核酸内切酶分型检测宫颈癌活检组织中ＨＰＶ－ＤＮＡ和ＨＳＶ－ＤＮＡ基因,以正常宫颈组织作对照。结果 在宫颈癌活检细胞中ＨＰＶ－１６,１８型和ＨＳＶ－２型阳性率分别为３８．９％和３４．６％,与正常妇女宫颈组织阳性率均为３．２％比较,差异均有非常显著意义（Ｐ〈０．００１）。结论 ＨＰＶ－１６     

Detection of human papillomavirus genotypes with liquid bead microarray in cervical lesions of northern Chinese patients

Human papillomavirus (HPV) is the main cause of cervical cancer. Blending multiplex polymerase chain reaction (PCR) amplification and multiplex hybridization to liquid bead microarray (LBMA), we detected and identified 25 common HPV genotypes using type-specific primers for HPV E6 and E7 genes in cervical lesions of northern Chinese patients. Of the 511 cervical samples, 349 (68.3%) were found to be HPV positive by HPV-LBMA. The distribution was 22 HPV positive of 100 in the control group (22%), 41 of 80 with chronic cervicitis (51%), 80 of 99 with cervical intraepithelial neoplasia (CIN) I (81%), 46 of 56 with CIN II (82%), 67 of 74 with CIN III (90%), and 93 of 102 with invasive cervical carcinoma (91%). HPV-16 was the most frequent genotype in the CIN and cervical cancer groups. The most common genotypes were HPV-16 (28%), HPV-58 (14%), HPV-52 (14%), HPV-18 (8%), and HPV-33 (7%) in the CIN group, and HPV-16 (63%), HPV-52 (9%), HPV-18 (7%), HPV-58 (7%), and HPV-33 (5%) in the cervical cancer group. HPV-LBMA found multiple genotypes in 1 of 22 control (4%), 64 of 193 CIN (33%), and 22 of 93 cervical cancer (24%). The HPV-LBMA results were compatible with those of PCR and DNA sequencing. HPV-LBMA is a simple, high-throughput method that provides useful information on viral genotype and multiple HPV infections in cervical lesions. In northern China, the most common high-risk HPV genotypes seem to be HPV types 16, 58, 52, 18, and 33. Genetic information on HPV in cervical specimens could provide particular benefits in the management of cervical lesions.     

High prevalence of human papillomavirus type 58 in Chinese women with cervical cancer and precancerous lesions.

The prevalence of human papillomavirus (HPV) among 332 Hong Kong Chinese women with abnormal Papanicolaou smears were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The overall HPV positive rate was 44.3% with 18.6% (16/86) for normal/inflamed cervices, 36.4% (32/88) for condyloma, 64.7% (33/51) for cervical intraepithelial neoplasia grade 1 (CIN 1), 37.9% (11/29) for CIN 2, 68.3 (41/60) for CIN 3, and 77.8% (14/18) for carcinoma. Double HPV infection was detected in 17 of the 147 positive samples, with a significantly higher proportion in patients with normal or inflamed cervices than those with CIN or carcinoma (31.3% vs 10.5%, P =.029). The six most commonly identified genotypes were HPV 16 (33.3%), HPV 58 (23.8%), HPV 11, 18, 31 (8.8% each), and HPV 33 (6.8%). The worldwide uncommon genotype HPV 58 was found to be the second most common genotype detected in patients with cervical carcinoma (6 of 18 patients). HPV 58 infection showed a significant association with CIN/carcinoma (odds ratio [OR] = 3.98; 95% confidence interval [CI] = 1.22-14.35) and a significant trend of increase in prevalence with increasing severity of cervical lesion (chi(2) = 5.84; P =.016). Among Hong Kong Chinese women with abnormal cervical cytology, the detection of HPV 58 carried a positive predictive value of 68.6% for a cervical lesion of CIN 1 or higher severity. The high prevalence of HPV 58 among Chinese women, particularly in patients with carcinoma, has an implication on the design of HPV detection methods and the development of vaccines.     

Association of HPV infection with prognosis after neoadjuvant chemotherapy in advanced uterine cervical cancer

Whether the human papillomavirus (HPV) status of the tumor affects the sensitivity to neoadjuvant chemotherapy, and the prognosis in advanced uterine cervical cancer (FIGO stage III or higher) remains unknown. We examined the HPV status of 43 patients who had received CDDP therapy by balloon-occluded arterial infusion (BOAI), as neoadjuvant chemotherapy for advanced uterine cervical cancer (squamous cell carcinoma) stage III or higher. DNA was extracted from formalin-fixed, paraffin-embedded tumor samples obtained by punch biopsy before the neoadjuvant chemotherapy. The detection of HPV and its typing were analyzed by a polymerase chain reaction (PCR)-based assay using consensus primers for the L1 consensus regions. HPV DNA was detected in all 43 patients (100%): 29 cases with HPV 16 (67.4%), 5 cases with HPV 33 (11.6%), 4 cases with HPV 31 (9.3%), 3 cases with HPV 35 (7.0%), 1 case with HPV 18 (2.3%) and 1 case with HPV 58 (2.3%). The HPV types were divided into 3 groups, HPV 16, HPV 33 and other HPV types (HPV 18, 31, 35, 58), and comparisons and examinations were performed among the 3 groups. Although the rates of tumor reduction and operation accomplishment after 3 courses of BOAI showed no significant differences among the 3 groups, there were significant differences in the survival rates. The survival rate of advanced uterine cervical cancer patients with HPV 33 infection was the highest, followed by that of patients with HPV 16 infection. The survival rates of patients with the other types of HPV infection were the worst among the 3 groups and significantly lower than those of patients with HPV 16 or HPV 33 infection. The differences in the curative effect after BOAI may depend on the different characters of the HPV types.     

Clinical efficacy of human papillomavirus DNA detection in urine from patients with various cervical lesions

A considerable number of adult Korean women avoid a Pap smear due to fear and discomfort of the pelvic examination. A reliable but noninvasive and comfortable screening method would considerably increase the participation rate. To evaluate the clinical efficacy of urine-based human papillomavirus (HPV) detection by oligonucleotide microarray, the results of HPV test from matched cervical swab specimens were compared. HPV DNA was detected in 70 of 100 cervical samples. HPV 16 was the most prevalent type (38/70), followed by types 18, 58, 52, 33, 35, 31, and 51. HPV DNA was identified in 47 of 90 urine samples. HPV 16 was the most prevalent type (30/45), followed by types 18, 52, 35, 51, 58, 33, and 56. The HPV detection rates of the cervical swabs increased in accordance with the severity of the cytologic and histologic diagnosis. The type specific agreement of HPV DNA tests between cervical swabs and urine was good in HPV 16 (kappa index=0.64 [95% CI: 0.50-0.79]), 18, 52, and 58 and fair in HPV 33 and 35. We propose that a urine HPV test is a valuable adjunctive method for a conventional Pap smear and can be used in population screening for cervical cancer in countries where it is difficult to obtain colposcopic specimens for cultural or religious reasons.     

High prevalence of intermediate-risk human papillomavirus infection in uterine cervices of Kenyan women infected with human immunodeficiency virus

The aim of this study was to investigate an association between certain human papillomavirus (HPV) types and human immunodeficiency virus (HIV) infections. Sexually active females (n = 487; 19-61 years old) were enrolled in the study. Subjects underwent Pap testing and evaluations of HIV and HPV infection status on uterine cervical cell samples. HPV genotyping was performed using a Kurabo GeneSQUARE DNA microarray test. Overall, 23 HPV genotypes were detected, and the most prevalent HPV genotype was HPV-52, followed by HPV-39, -54, -45, -56, -53, -31, -42, -16, -68, and -51. HPV-30, -53, -54, -61, and -66, which are associated with abnormal cytology, are categorized as intermediate-risk in this study. Detection of both high- and intermediate-risk HPV types was significantly associated with cervical abnormality and HIV infection. Multivariate analysis revealed that some high-risk HPV types (HPV-31, -45, -51, -56, and -59) and most intermediate-risk HPV types were associated with HIV infection, while the high-risk types (HPV-16, -18, -33, -35, -39, -52, -58, and -68) were not. The oncogenic effect of the most malignant HPV types (e.g., HPV-16 and -18) appear to be lower, while that of intermediate-risk types are greater, in areas with a high prevalence of HIV infection.     

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.     

Genotype spectrum of cervical human papillomavirus infection among sexually transmitted disease clinic patients in Hong Kong

Previous studies have suggested that a few uncommon human papillomavirus (HPV) genotypes are prevalent in Chinese cervical cancer patients. To elucidate the genotype spectrum of HPVs circulating among Hong Kong Chinese, a cross-sectional study was conducted on 553 women who attended a public sexually transmitted disease clinic. HPV DNA was detected from cervical samples using the polymerase chain reaction, followed by genotype identification based on restriction fragment length polymorphism and direct sequencing. The prevalence of HPV was 30.6% for all types combined, 14.8% for high-risk types, 10.8% for low-risk types, and 7.1% for unknown-risk types. Among the HPV-positive women, 89.9% had single type infections; whereas the other 10.1% harboured more than one HPV type. HPV11 was the most prevalent genotype, detected in 5.1% of subjects; followed by HPV16 (4.9%), HPV58 (4.3%), HPV6 (3.3%), and HPV53 and CP8304 (2.2% each). Other less common genotypes found were HPV18, 33, 39, 61, LVX160, MM4, MM7 (range: 0.7-1.6%); HPV26, 45, 54, 56, 59, and LVX100 (range: 0.4-0.5%); HPV35, 40, 52, 55, 68, MM8, and MM9 (0.2% each). This study shows that HPV58 is the second most common high-risk HPV genotype circulating among Chinese female sexually transmitted disease clinic patients in Hong Kong. This together with previous reports of the high prevalence of HPV58 among Chinese cervical cancer patients accentuate the importance of developing vaccines targeting at this otherwise uncommon genotype.