免疫细胞及肿瘤标志物与高危型HPV感染宫颈癌患者HPV水平的相关性及与预后的关系

目的探讨免疫细胞及肿瘤标志物与有高危型人乳头瘤病毒(HPV)感染的宫颈癌患者HPV水平的相关性及与预后的关系。方法选取有HPV感染的72例宫颈癌患者(宫颈癌组)、83例宫颈上皮内瘤变(CIN)患者(CIN组)和50例慢性宫颈炎患者(慢性宫颈炎组)。比较不同宫颈疾病患者外周血免疫细胞(CD4^+、CD8^+、CD4^+/CD8^+、CD56^+、Treg)水平和肿瘤标志物(K-ras、Ki-67)的阳性表达情况,高危型HPV宫颈癌患者HPV水平与免疫细胞及肿瘤标志物的相关性,以及有无淋巴结转移的高危型HPV感染宫颈癌患者的免疫细胞水平及肿瘤标志物阳性表达情况,宫颈癌死亡患者与生存患者的免疫细胞水平及肿瘤标志物阳性表达情况。结果宫颈癌组患者的CD4^+、CD56^+、CD4^+/CD8^+水平均低于CIN组患者和慢性宫颈炎组患者(P﹤0.05),CD8^+、Treg的水平均高于CIN组患者和慢性宫颈炎组患者(P﹤0.05);3组患者的K-ras、Ki-67的阳性表达率比较,差异均有统计学意义(P﹤0.05);宫颈癌组患者的CD8^+、Treg水平及K-ras、Ki-67阳性表达情况与HPV-DNA水平呈正相关(r=0.546、0.402、0.645、0.713,P﹤0.05),而CD4^+、CD56^+水平与HPV-DNA水平呈负相关(r=-0.478、-0.463,P﹤0.05);宫颈癌组有淋巴结转移的患者CD4^+、CD56^+、CD4^+/CD8^+水平均明显低于无淋巴结转移的患者(P﹤0.01),而CD8^+、Treg的水平及K-ras(+++)、Ki-67(+++)的比例均高于无淋巴结转移的患者(P﹤0.05);宫颈癌组死亡患者的CD4^+、CD4^+/CD8^+、CD56^+水平均明显低于生存患者(P﹤0.01),而CD8^+、Treg的水平及K-ras(+++)、Ki-67(+++)的比例均明显高于生存患者(P﹤0.01)。结论与有高危型HPV感染的CIN患者和慢性宫颈炎患者比较,有高危型HPV感染的宫颈癌患者的免疫功能降低,而其肿瘤标志物K-ras、Ki-67表达升高,免疫细胞和肿瘤标志物的检测有助于高危型HPV感染宫颈癌患者的早期预防、诊断及预后评估。     

珠海地区妇女宫颈上皮内瘤变与高危型人乳头瘤病毒亚型关系的初步研究

目的探讨珠海地区妇女宫颈上皮内瘤变与高危型人乳头瘤病毒亚型的关系。方法采用杂交捕获二代（HC-Ⅱ）方法定量检测珠海地区宫颈疾病患者HPV-DNA的含量,全部269例患者阴道镜下多点取活组织病理检查,根据病理学诊断结果分组。结果珠海地区高危型HPV在慢性宫颈炎、C INⅠ、C INⅡ及C INⅢ的感染率分别为13.5%、48.2%、73.8%及93.7%,HPV16在四组中感染率依次为3.6%、13.4%、47.6%及65.6%,宫颈病变存在多重HPV感染。结论珠海地区宫颈上皮内瘤变患者感染HPV16、18、31、58及35型较多见,多重HPV感染可能促进宫颈上皮内瘤变的发生。     

不同人乳头瘤状病毒亚型感染与宫颈癌及宫颈上皮内瘤变严重程度的关系分析

目的 探讨不同人乳头瘤病毒(HPV)亚型感染与宫颈癌及宫颈上皮内瘤变严重程度的关系.方法 选取2018年6月至2020年12月间宝鸡市中医医院收治的287例行宫颈组织学检查的宫颈疾病患者,均行HPV检测,比较宫颈癌或宫颈高级别病变患者不同HPV亚型感染率,通过Logistic回归方法分析宫颈癌、宫颈高级别病变与不同HP...     

广东妇女人乳头瘤病毒感染及宫颈细胞学的对照研究

目的探讨人乳头瘤病毒(HPV)与宫颈癌的相关性及HPV检测在宫颈癌筛查中的应用。方法用第二代杂交捕获法(HCⅡ)检测2636名妇女宫颈刷出物中13种高危型HPV,其中454例同时做宫颈脱落细胞液基薄层细胞学检测(TCT)。细胞学诊断采用Bethesda分级系统(TBS)。结果2636名妇女高危型HPV感染率为26.5%,其中20岁以下(含20岁)年龄组的高危型HPV感染率最高(59.4%),41～50岁年龄组最低(21.0%)。新会地区HPV感染率显著低于东莞、深圳和广州(P<0.01)。16例宫颈癌患者HPV感染率为93.8%,显著高于健康体检者(19.2%)和宫颈炎患者(30.8%,P<0.001)。454例同时做TCT检查的妇女中,鳞状细胞癌(SCC)、高度鳞状上皮内瘤变(HSIL)、低度鳞状上皮内瘤变(LSIL)、不典型鳞状细胞(ASC)的高危型HPV检出率分别为100%(2/2)、100%(12/12)、88.9%(16/18)和37.8%(28/74)。HPV阳性检出率随病变的严重程度而显著增加。结论高危型HPV是宫颈病变的重要病因学因素,可能诱发宫颈癌,HPV检测是筛查宫颈癌的一种有效辅助方法;HPV感染率的年龄和地区性差异可能和受检者不同生活方式有关。     

年轻女性宫颈人乳头瘤病毒感染亚型与宫颈病变的调查

目的：探讨年轻女性（年龄25~35岁）人乳头瘤病毒（HPV）感染亚型与宫颈病变的特点。方法采集1273例患者宫颈上皮细胞标本,采用PCR-反向点杂交法对其进行21种HPV分型的检测。结果1273例年轻女性患者,HPV阳性有130例,检出率为10.2%;单一型感染为115例,包括高危型感染105例,感染率为91.3%,低危型感染10例,感染率为8.7%;最常见高危型是HPV16,共35例,其次为HPV58,共17例;HPV16感染导致宫颈高级别上皮内瘤变10例,低级别上皮内瘤变11例;高危HPV阳性患者,宫颈活检证实为鳞状细胞癌的病例2例,均是HPV16感染。结论年轻女性HPV阳性检出率较高,以单一型感染和高危型感染为主,高危型HPV感染与宫颈高级别上皮内瘤变和宫颈癌的发生密切相关,其中HPV16亚型是导致年轻女性宫颈癌的主要原因。     

人乳头状瘤病毒检测在宫颈癌和宫颈癌前病变筛查中的应用

目的探讨人乳头状瘤病毒(HPV)检测在宫颈癌及宫颈癌前病变筛查中的应用效果。方法选择2014年8月至2015年8月间在海口市中医院检验科行宫颈癌病变检查的220例患者进行宫颈癌筛查,采用二代杂交捕获技术(HC-2)检测HPV感染情况。结果病理检查结果显示,220例患者中,宫颈癌80例(36.4%),宫颈上皮内瘤变(CIN)Ⅰ级40例(18.2%),CINⅡ级~CINⅢ级80例(36.4%)和慢性宫颈炎20例(9.1%)。宫颈癌、CINⅠ级、CINⅡ级~Ⅲ级和慢性宫颈炎患者HPV阳性率分别为100.0%(80/80)、75.0%(30/40)、95.0%(76/80)和30.0%(6/20)。宫颈癌患者HPV DNA水平显著高于CINⅡ~Ⅲ级、CINⅠ级和宫颈炎患者,差异有统计学意义(P<0.05)。CINⅡ~Ⅲ级和CINⅠ级患者HPV DNA水平显著高于宫颈炎患者,差异有统计学意义(P<0.05)。结论HPV检测可作为预测CIN和宫颈癌的重要指标,值得临床推广应用。     

宫颈癌患者人乳头瘤病毒感染分布特点

目的:探讨人乳头瘤病毒(HPV)各亚型在广西沿海地区宫颈癌患者中的分布情况,HPV感染与宫颈癌患者的年龄、临床分期、病理类型、分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发的关系。方法:通过凯普导流杂交HPV DNA检测法,对76例宫颈癌患者宫颈脱落细胞进行21种HPV亚型的检测。结果:宫颈癌HPV总阳性率为90.8%。宫颈癌患者HPV阳性各亚型出现的频率排序为:HPV16(56.5%),HPV18、33、58各(7.2%),HPV52、53各(5.8%),HPV31(4.3%),HPV45(2.9%),HPV35、51、56、66、68各(1.4%)。HPV6(5.8%),HPV11、44、43各(1.4%)均合并在高危感染中。HPV感染与临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发关联无显著性(P>0.05),与年龄密切相关,鳞癌HPV阳性率明显高于腺癌及其它癌,差异有统计学意义(P<0.05)。结论:广西沿海地区妇女宫颈癌患者中以HPV16、18、33、58感染为主要型别。HPV感染与宫颈癌的临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发无明显相关性,与发病年龄、病理类型有关。     

高龄妇女宫颈疾病与人乳头瘤病毒感染相关性

[目的]探讨高龄妇女子宫颈疾病的人乳头瘤病毒(HPV)感染状况、类型,尤其是在宫颈癌前期病变及宫颈癌中的特点.[方法]应用PCR法检测267例高龄宫颈癌、宫颈上皮内瘤变(CIN)患者及正常妇女HPV感染率并分型,比较各型HPV在宫颈疾病中的感染情况.[结果]高龄妇女CIN和宫颈癌患者HPV感染率较对照组明显升高(46.15%,89.83%,3.45%),但低于常龄者;高龄宫颈癌和CIN患者HPV感染以16、18型为主,CIN者感染率分别为33%和8%,浸润癌分别为45%和15%,31,33,52,58型也呈较高值.[结论]①高龄妇女HPV感染率低于常龄者,多种类型的HPV感染并不呈持续状态.②高龄宫颈癌患者的非HPV感染因素较育龄妇女比例增高.③高龄妇女HPV感染类型呈现明显的多样性,可能与不同类型HPV生存特性相关.     

人乳头瘤病毒与人类宫颈癌

鉴于人乳头瘤病毒（HPV）与人类宫颈上皮内瘤样病变以至宫颈癌的发病有密切的关系，为此作者复习相关文献，就HPV的结构、女性生殖道HPV感染的流行病学、HPV感染与宫颈癌的关系等方面加以扼要的综述。     

高危型人乳头瘤病毒对宫颈癌及癌前病变诊断价值的探讨

为了探讨高危型人乳头瘤病毒(HPV)检测在宫颈癌及癌前病变中的诊断价值,采用第2代杂交捕获(HC-2)技术对325例妇科疾病患者[慢性宫颈炎56例,宫烦上皮内瘤变(CIN)Ⅰ41例,CIN Ⅱ 33例,CIN Ⅲ 91例,宫颈癌104例]进行HPV DNA阳性率和含量浏定.慢性宫颈炎、CIN Ⅰ级、CIN Ⅱ～Ⅲ级和宫颈癌患者HPV阳性感染率分别为35.7%,61.0%,91.0%和100.0%o;宫颈癌前病变(CIN I～Ⅲ)和宫颈癌的HPV DNA含量均明显高于慢性宫颈炎,差异有统计学意义,P＜0. 05;宫颐癌的HPV DNA含量明显高于宫颈癌前病变(CINⅠ～Ⅲ),差异有统计学意义,P＜0.05.初步研究结果提示,HPV DNA阳性感染率随宫颈病变程度的加重而升高;高危型HPV在慢性宫颈炎、CIN和宫颈癌中的病毒含量随宫颈病变程度的加重呈上升趋势.高危型HPV可以作为宫颈癌及癌前病变的重要检测指标.     

Occurrences of human papilloma virus DNA in cervical carcinomas

Out of 16 cases involving a cervical carcinoma that were investigated by Southern blot hybridization, found were human papilloma virus (HPV) types 16 and 18 DNA sequences in 8 (50%) and in one (6.3%), respectively. Six out of the 8 HPV 16-positive specimens were from squamous cell carcinomas, one was from an adenocarcinoma, and the remaining specimen was from an argyrophil small cell carcinoma. In 7 out of 9 HPV-positive specimens, the viral sequences were integrated in the tumor cell genome, whereas in the remaining two they were not integrated and remained circular and/or oligomeric in form.     

Genotypes of human papilloma virus in Sudanese women with cervical pathology

Background  

Knowledge of the distribution of human papillomavirus (HPV) genotypes among women with cervical lesion and in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. There is no published data concerning HPV and cervical abnormalities in Sudan. This study aimed to define the prevalence of HPV and its subtypes in the cervical smears of women presenting with gynecological complains at Omdurman Military Hospital, Sudan.     

High-risk human papilloma virus and cervical abnormalities in HIV-infected women with normal cervical cytology

Background

The prevalence of High-Risk Human papilloma virus (HR-HPV), a necessary cause of invasive cervical cancer (ICC) is relatively high in HIV infected women. Gaps exist in our knowledge of the optimal approaches for managing women who have HR-HPV with normal cervical cytology (NCC) particularly in settings of HIV infection.

Methods

Between May 2012 and June 2013 we conducted a colposcopic assessment of HIV-infected women with prior (NCC) and known HR-HPV status to compare cervical abnormalities in women with and without HR-HPV. Colposcopic examinations were done at the Operation Stop Cervical Cancer (OSCC) unit of the Jos University Teaching Hospital (JUTH), Jos, Nigeria. Abnormal colposcopic finding (ACF) was defined as areas of aceto-white epithelium involving the squamo-coulumnar junction, areas of punctation, mosaic pattern or atypical vessels. We compared proportions of ACF as well as histologic grades of cervical intra-epithelial neoplasia (CIN) in women with or without HR-HPV. Statistical analysis was done on STATA.

Results

We conducted colposcopic examinations in 78 out of 89 (86.5%) eligible women. The mean age of the cohort was 32.4 years (SD ±4.6) with a median 32 years (IQR 29–36). After a mean follow up time of 20.1 months from the initial cervical pap cytology and HR-HPV testing, we found 12 of 78 (15.4%) women with ACF. The odds for an ACF was statistically higher [OR = 4.0 (95% CI: 1.1-14.7)] in women with HR-HPV compared to those without. Of the twelve women with ACF, subsequent histologic examination of colposcopically directed cervical biopsies confirmed CIN 1 in 4 cases (33.3%), CIN 2 in 1 case (8.3%), CIN 3 in 2 cases (16.7%), carcinoma-in-situ (CIS) in 2 cases (16.7%), and normal cervix in 3 (25.0%). Overall, the proportion of women detected with any grade of CIN was 11.5% (9/78) and 6.4% (5/78) were CIN 2 or greater lesion (CIN2+).

Conclusion

HIV-infected women with NCC and HR-HPV had a four-fold higher likelihood for an ACF. The practice of early colposcopic examination of HIV-infected women with prior NCC and HR-HPV may increase early detection of higher grade CIN and CIS cancer stages in our setting.

     

cobas 4800 HPV检测在宫颈癌筛查中的应用价值

  目的  评价cobas 4800 HPV检测技术在宫颈癌及癌前病变筛查中的可行性及应用价值。  方法  对河南省新密市856例年龄 > 21岁有性生活的妇女进行宫颈癌筛查。每位妇女均接受了cobas 4800 HPV检测、高危型HPV第二代杂交捕获试验(hy brid capture 2 technology, HC2)检测、ThinPrep液基细胞学和阴道镜检查。阴道镜下在可见病变处直接取活检; 任意筛查结果阳性但无可见病变时, 于宫颈外口鳞柱交界处行四象限随机活检和宫颈管搔刮术(endocervical curettage, ECC)。  结果  cobas 4800HPV检测与HC2检测对宫颈上皮内瘤变(cervical intraepithelial neoplasia, CIN)2级以上(CIN2、CIN3及宫颈癌)患者的灵敏度均为94.4%(34/36), 特异度分别为63.2%(516/817)和63.9%(522/817);一致率为83.4%(711/853), 两者具有高度一致性(Kappa=0.65)。cobas 4800 HPV检测对于液基细胞学检查漏诊的患者具有100%检出率。cobas 4800 HPV16及18分型检测对于CIN2以上患者的阳性预测值21.9%为HC2检测10.3%的2.13倍。妇女感染HPV16及18型患CIN2以上病变的年龄比感染其他类型平均小5.4岁。  结论  cobas 4800 HPV检测与HC2检测具有相似的准确性和良好的一致性, 比ThinPrep液基细胞学检查更为灵敏, 并且能鉴别HPV16及18两种高风险类型HPV感染, 利于医生更有针对性地随访宫颈病变中的高危病例。      

Prevalence of cervical human papilloma virus infection among married women in Vietnam, 2011

The burden of cervical cancer is increasing in Vietnam in the recent years, infection with high risk HPV being the cause. This study aimed to examine the prevalence of HPV and the distribution of HPV specific types among the general population in 5 big cities in Vietnam. Totals of 1500 women in round 1 and 3000 in round 2 were interviewed and underwent gynecological examination. HPV infection status, and HPV genotyping test were performed for all participants. Results indicated that the prevalence of HPV infection in 5 cities ranged from 6.1% to 10.2% with Can Tho having highest prevalence. The most common HPV types in all 5 cities were HPV 16, 18 and 58. Most of the positive cases were infected with high risk HPV, especially in Hanoi and Can Tho where more than 90% positive cases were high risk HPV. Furthermore, in Can Tho more than 60% of women were infected with multiple HPV types. The information from this study can be used to provide updated data for planning preventive activities for cervical cancer in the studied cities.     

宫颈脱落细胞检查联合人乳头瘤病毒检测对诊断宫颈癌的临床意义

目的探讨宫颈脱落液基细胞学检查(TCT)联合人乳头瘤病毒检测(HPV-DNA)诊断宫颈癌的临床意义。方法选取2012年5月至2015年5月间海南省文昌市人民医院收治的100例宫颈癌患者,分别单独行TCT检测、单独HPV-DNA检测、HPV-DNA+TCT检测,比较3种检测方法的诊断结果。结果 HPV-DNA+TCT检测宫颈癌的阳性率为81.0%,显著高于单独TCT检测的51.0%和单独HPV-DNA检测的55.0%,差异有统计学意义(P<0.05);单独TCT与单独HPV-DNA检测的阳性率间差异无统计学意义(P>0.05)。结论 TCT和HPV-DNA联合诊断宫颈癌阳性符合率较高,具有显著的临床应用价值。     

Presence of human papilloma virus types 16 and 18 in genital warts and cervical neoplasias

Certain types of human papilloma viruses (HPV) are associated with human genital proliferative diseases, and among them HPV16 and HPV18 seem to play an important role in the occurrence of cervical cancer. We used restriction enzyme analysis and molecular hybridization, in order to investigate the type of viral infection and the physical state of viral DNA in gynecological benign, pre-malignant and malignant lesions. HPV6/11 specific sequences could only be detected as episomes and this in benign lesions classified as condylomata acuminata. On the other hand, HPV16 and HPV18 sequences were detected in non-malignant lesions such as flat condylomata (7 out of 14 cases), pre-malignant lesions including cervical intra-epithelial neoplasias (10 out of 20 cases), and most frequently in cervical invasive cancers (21 out of 27 cases). In a large number of virus-positive cases, HPV16 and HPV18 could only be discerned in forms consistent with the existence of episomes and/or randomly integrated head-to-tail oligomers. However, some invasive carcinomas and cervical intra-epithelial neoplasias contained, in addition, clonal outgrowths with detectable virus-cellular junction fragments of the integrated viral genomes. In the light of these data, monitoring the type of viral infection proves to be an important adjunct to histological analysis when assessing those patients affected by condyloma or cervical intra-epithelial neoplasia who are at risk for developing invasive carcinoma.     

液基细胞学联合HPV分型检测在妊娠合并宫颈上皮内瘤变患者的应用

  目的  应用液基细胞学联合HPV分型方法检测妊娠合并宫颈上皮内瘤变(Cervical intraepithelial neoplasia, CIN), 初步了解此类患者中TCT及HPV感染情况与妊娠宫颈病变的关系。  方法  对象为2006年1月至2012年1月确诊为妊娠合并宫颈上皮内瘤变的72例患者, 初次孕期保健均进行细胞学、HPV检测, 对这些临床资料进行回顾性分析研究。  结果  妊娠合并CIN发生率为2.1%。72例患者中全部产前行宫颈TCT检测, HSIL为32例, LSIL为40例, 56例于产前保健时检测HPV, 其中48例(85.7%)为阳性结果, 32例为HPV16型单独或混合感染。72例孕期保健时行阴道镜活检病理诊断CINⅠ16例、CINⅡ16例、CINⅢ40例。  结论  液基细胞学联合HPV分型检测在妊娠合并宫颈上皮内瘤变患者的应用是安全而且有效的。在妊娠期CIN患者中HPV感染率高, 且HPV16型与CIN高等级病变关系密切。      

Nitrative and oxidative DNA damage in cervical intraepithelial neoplasia associated with human papilloma virus infection

Recently, it was proposed that inflammation plays an integral role in the development of human papilloma virus (HPV)-induced cervical cancer. The present study sought to examine if 8-nitroguanine, a mutagenic nitrative DNA lesion formed during inflammation, contributes to cervical carcinogenesis. We obtained biopsy specimens from 30 patients with cervical intraepithelial neoplasia (CIN)1 (n = 9), CIN2 (n = 10), CIN3 (n = 6) and condyloma acuminatum (n = 5). We used immunohistochemistry to detect the formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion, and compared it with the expression of the cyclin-dependent kinase inhibitor p16, which is considered to be a biomarker for cervical neoplasia. Double immunofluorescence labeling revealed that 8-nitroguanine and 8-oxodG were colocalized in cervical epithelial cells. Samples from CIN2-3 patients, most of whom were infected with high-risk HPV subtypes, exhibited significantly more intense staining for 8-nitroguanine than those with condyloma acuminatum. 8-Nitroguanine and 8-oxodG immunoreactivities correlated significantly with the CIN grade. We observed the expression of inducible nitric oxide synthase in epithelial and inflammatory cells from CIN lesions. Proliferating cell nuclear antigen was expressed specifically in dysplastic epithelial cells, but not in those of condyloma acuminatum. There were no statistically significant differences in p16 expression between CIN and condyloma acuminatum samples. These results suggest that high-risk HPV types promote inducible nitric oxide synthase-dependent DNA damage, which leads to dysplastic changes and carcinogenesis; in contrast, p16 appears to be merely a marker of HPV infection. Thus, 8-nitroguanine is a more suitable and promising biomarker for evaluating the risk of inflammation-mediated cervical carcinogenesis than p16.