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。      

宫颈癌早期筛查方法研究进展

宫颈癌是严重威胁妇女健康的恶性肿瘤之一。近年来宫颈癌发病率逐年增加,且宫颈癌患者日益年轻化,因此,寻找宫颈癌的早期筛查方法尤为重要。本文主要就目前比较常用的方法和近年出现的新方法加以介绍,包括宫颈细胞涂片形态检测、人乳头瘤病毒检测、阴道镜检测、分子细胞遗传学检测、宫颈癌筛查系统。     

液基细胞学筛查宫颈癌的研究

目的 评价ThinPrep液基细胞学在宫颈癌高发区筛查的准确性。方法 1997年例受检者同时做宫颈脱落细胞液基标本采集和阴道镜活检,用液基标本做薄片细胞学诊断和肿瘤相关人乳头瘤病毒（human papilloma virus,HPV)检测。细胞学诊断采用TBS分级系统,阳性诊断包括意义不明的不典型鳞状细胞（ASCUS）以上病变,诊断结果与阴道活检诊断和肿瘤相关HPV DNA阳性检出率对照。所有检查均双盲进行。结果 ThinPrep液基细胞学检出100％（12／12）的鳞状细胞癌（SCC）;93．2％（69／74）的鳞状上皮内高度病变（HSIL）,其中CIN396．8％（30／31）,CIN90．7％（39／43）;72．4％（92／127）的鳞状上皮内低度病变（LSIL）。SCC和CIN3的分级准确率分别达100％和87．1％。HPVDNA阳性检出率与细胞学分级密切相关,且在细胞学与组织学相同级别基本一致。结论 宫颈液基标本收集方法有利于细胞学和肿瘤相关HPV DNA双重检查。ThinPrep液基细胞学检查敏感性高,尤其是对鳞状上皮内高度病变。     

高危型人乳头瘤病毒在女性感染者中的分布特征及其用于筛查宫颈癌的价值分析

目的分析人乳头瘤病毒在女性感染者中的分布特征,评估HPV-DNA分型检测用于筛查宫颈癌的临床价值。方法选择行宫颈癌筛查的患者2560例。采集患者宫颈细胞进行HPV-DNA检测,对HPV-DNA高危型阳性患者行液基细胞学(TCT)检测,TCT阳性者行阴道镜取活检病理检测。结果 2560例妇女中共检测出HPV-DNA阳性者711例(27.8%),其中高危型265例(10.4%),低危型446例(17.4%)。不同分级宫颈病变中HPV类型感染分布差异有统计学意义(P<0.05)。HPV-DNA高危型感染以30岁以下和50岁以上的人群感染率较高,各年龄段患者HPV-DNA高危型感染率差异无统计学意义(χ~2=5.673,P=0.339)。HPV-DNA高危型感染者中病理诊断为宫颈癌患者10例(3.8%),低危型感染者中病理诊断为宫颈癌者2例(0.4%),二者差异有统计学意义(P<0.05)。TCT联合HPV-DNA分型检测的敏感度高于二者单独检测,特异度和假阳性率低于HPV-DNA分型检测,假阴性率低于二者单独检测,差异均有统计学意义(P<0.05)。结论高危型HPV检测用于筛查宫颈癌敏感性和特异性高,可作为辅助宫颈细胞学检测的手段,临床应用价值较高。     

高危型人乳头瘤病毒检测用于宫颈癌筛查相关心理问题的研究进展

高危型人乳头瘤病毒（high-risk human papillomavirus，HRHPV）检测是当今世界宫颈癌筛查的主要方式之一，其对宫颈高级别病变及宫颈癌的检测敏感度优于传统细胞学筛查。随着hrHPV筛查阳性的人数增多，人群的心理健康问题也日益受到关注。由于hrHPV同时具备性传播感染和宫颈癌致病因素的属性，在信息不对等时，可能使患者表现出过于焦虑、羞愧而拒绝配合检查；这种表现多为短期影响，且可以通过改进沟通方式或取样技术而改善。本文就国内外相关研究进展作一综述。     

筛查——宫颈癌的防治“捷径”

一般来说,宫颈癌病例均与人乳头瘤病毒（HPV）感染相关。但不是所有感染了HPV的妇女都会患上宫颈癌,通常情况下,这类感染可能无需治疗便自行消失,但持续感染高危类型的HPV达12个月以上则会增加患宫颈癌的风险。     

宫颈癌的基因治疗

宫颈癌是最常见的妇女恶性肿瘤之一,人乳头瘤病毒(human papilloma virus,HPV)持续感染是宫颈癌发生的重要因素.传统治疗手段包括手术、放射治疗和化疗,但是对于晚期宫颈癌和放化疗不敏感的患者,治疗效果仍不理想.近年来,多个实验室从基因水平对宫颈癌治疗进行了大量研究和探索,本文对宫颈癌基因治疗的主要进展及其与传统治疗联合应用的相关文献进行综述.     

Detection of High-Risk Human Papillomaviruses in the Prevention of Cervical Cancer in India

Human papillomaviruses (HPVs) are small, non-enveloped, double-stranded DNA viruses that infect epithelial tissues. Specific genotypes of human papillomavirus are the single most common etiological agents of cervical intraepithelial lesions and cervical cancer. Cervical cancer usually arises at squamous metaplastic epithelium of transformation zone (TZ) of the cervix featuring infection with one or more oncogenic or high-risk HPV (HRHPV) types. A hospital- based study in a rural set up was carried out to understand the association of HR-HPV with squamous intraepithelial lesions (SILs) and cervical cancer. In the present study, HR-HPV was detected in 65.7% of low-grade squamous intraepithelial lesions (LSILs), 84.6% of high grade squamous intraepithelial lesions (HSILs) and 94% of cervical cancer as compared to 10.7% of controls. The association of HPV infection with SIL and cervical cancer was analyzed with Chi square test (p<0.001). The significant association found confirmed that detection of HR-HPV is a suitable candidate for early identification of cervical precancerous lesions and in the prevention of cervical cancer in India.     

Exploring the Causes of the Low Incidence of Cervical Cancer in Western Asia

Anecdotal epidemiologic observations can provide valuable tools to study various biologic elements in complexdiseases such as cancer. Although cervical cancer is one of the most frequent malignancy affecting women in the world,it displays wide geographical variations remnant of socioeconomic, ethnic and genetic predisposing factors. The observedlow incidence of cervical cancer in western Asia has triggered scientists to try to delineate the causes of this reducedoccurrence. Although this region including Saudi Arabia is known for being conservative societies with low incidence ofsexually transmitted infections including human papillomavirus (HPV) and associated cervical cancer, scientificresearch points out multifaceted biological explanations including host genetic variations. Researchers observed thata protective genetic variant TP53 codon 72 proline allele was more commonly found in this population and appear tobe over-transmitted compared to others known for their high rate of cervical cancer. Thus, the combination of relativelow rate of HPV infection, over-transmission of protective genetic variant along with societal variables are the rationalebehind the low incidence of cervical cancer in women in the region of western Asia. The influence of the geneticmakeup of the patients has impact on personalized preventive medicine to gauge the risk of developing cervical cancer.     

江西地区妇女宫颈癌患者人乳头瘤病毒(HPV)感染各亚型分布特点

目的分析江西地区妇女宫颈癌患者人乳头瘤状病毒(human papillomavirus,HPV)感染分布情况及主要型别,为江西地区临床防治宫颈癌、研制适合该地区的预防性HPV疫苗提供理论依据。方法收集经病理确诊的941例宫颈癌患者治疗前宫颈脱落细胞,采用人乳头瘤病毒核酸扩增分型检测试剂盒方法,进行HPV分型检测。结果 941例宫颈癌患者中有780例HPV阳性,阳性率为82.9%,其中,单纯感染率为67.5%,混合感染率为15.4%,单纯高危感染率为66.6%。HPV16感染率最高为54.8%,宫颈癌中其他高危型的感染率从高到低依次为HPV58、18、52、31、33、39、53、45、51、68、59、66、56、35,未发现单纯HPV56感染。低危HPV型中HPV81型感染率最高为1.7%,其他低危型感染率从高到低依次为HPV44、6、42、11,未检测出低危型HPV43,且低危型HPV44仅存在于混合感染中。随着年龄增加,高危HPV16感染率呈逐渐下降趋势,差异有统计学意义(P=0.001,<0.05)。年龄≤50岁,HPV16感染率为59.5%,高于年龄>50岁HPV16感染率(50.7%),差异有统计学意义(P=0.007,<0.05)。年龄≤50岁HPV58感染率为6.7%,低于年龄>50岁HPV58感染率(11.7%),差异有统计学意义(P=0.019,<0.05)。而HPV亚型18、52、31分布均无差异。结论江西地区妇女宫颈癌患者中以HPV16、58、18、52感染为主要型别,HPV16感染是年轻宫颈癌的主要致病因素。混合感染并不增加宫颈癌的发生率。     

Application of Human Papillomavirus in Screening for Cervical Cancer and Precancerous Lesions

Cervical cancer is a commonly-encountered malignant tumor in women. Cervical screening is particularlyimportant due to early symptoms being deficient in specificity. The main purpose of the study is to assess theapplication value of cervical thinprep cytologic test (TCT) and human papillomavirus (HPV) detection in screeningfor cervical cancer and precancerous lesions. In the study, cervical TCT and HPV detection were simultaneouslyperformed on 12,500 patients selected in a gynecological clinic. Three hundred patients with positive resultsdemonstrated by cervical TCT and/or HPV detection underwent cervical tissue biopsy under colposcopy, andpathological results were considered as the gold standard. The results revealed that 200 out of 12,500 patientswere abnormal by TCT, in which 30 cases pertained to equivocal atypical squamous cells (ASCUS), 80 casesto low squamous intraepithelial lesion (LSIL), 70 cases to high squamous intraepithelial lesion (HSIL) and 20cases to squamous cell carcinoma (SCC). With increasing pathological grade of cervical biopsy, however, TCTpositive rates did not rise. Two hundred and eighty out of 12,500 patients were detected as positive for HPVinfection, in which 50 cases were chronic cervicitis and squamous metaplasia, 70 cases cervical intraepithelialneoplasia (CIN) Ⅰ, 60 cases CIN Ⅱ, 70 cases CIN Ⅲ and 30 cases invasive cervical carcinoma. Two hundred andthirty patients with high-risk HPV infection were detected. With increase in pathological grade, the positive rateof high-risk HPV also rose. The detection rates of HPV detection to CIN Ⅲ and invasive cervical carcinoma aswell as the total detection rate of lesions were significantly higher than that of TCT. Hence, HPV detection is abetter method for screening of cervical cancer at present.     

微小 RNA 在宫颈癌的早期筛查中的应用及预后价值研究

目的：研究微小RNA在宫颈癌的早期筛查中的应用及预后价值。方法采用实时定量PCR（定量PCR）测定宫颈癌肿瘤组织中miRNA的表达水平（miR-21,miR-27a,miR-34a,miR-155,miR-196a,miR-203）。结果 miR-27a在宫颈上皮内瘤变（CIN2-3）中的表达水平显著高于CIN1（P＝0．023）,而在鳞状细胞癌（SCC）中的表达水平高于CIN2-3（P＝0．033）。此外,miR-34a在CIN2-3中的表达水平显著低于CIN1（P＝0．041）,在SCC中的表达水平低于CIN2-3（P＝0．021）。与CIN1比较,CIN2-3的miR-27a表达水平上调（P＝0．028）而miR-34a表达水平下调,HPV16阳性与宫颈癌显著相关（CIN2-3／CIN1：P＝0．027;SCC／CIN2-3：P＝0．036）。 miR-34a的表达水平与吸烟状况和HPV16相关。结论检测miRNA表达水平有助于评估不同宫颈癌变和预测HPV感染结果。     

宫颈癌高发区新疆维吾尔族妇女宫颈癌组织中HPV DNA的测定

目的 研究我国宫颈癌高发区新疆维吾尔自治区维族妇女宫颈癌发病与人类乳头状瘤病毒（HPV）的关系。方法 对75例新疆维吾尔族宫颈癌患者癌组织及20例正常宫颈组织,采用PCR（聚合酶链反应）技术检测HPV－C（总的HPV）、HPV16、HPV18及HPV6／11。结果 HPV－C、HPV16、HPV18及HPV6／11在宫颈癌患者及正常宫颈组织中的检出率分别为86．7％、72．0％、12．0％、0及20．0％、10．0％、0、10．0％。HPV16在HPV阳性患者中所占的比例为83．1％,宫颈癌患者中HPV－C、HPV16检出率明显高于正常对照组,鳞癌HPV16阳性率明显高于腺癌,而腺癌HPV18检出率明显高于鳞癌（P＜0．05）。HPV总感染率及HPV16阳性率,在不同临床分期及不同病理分级宫颈癌组织间无显著性差异。结论 HPV感染与我国宫颈癌高发区新疆维吾尔族妇女宫颈癌发病有密切相关,其中HPV16感染在其发病中起主要作用,但HPV感染对宫颈癌的进展影响不大。     

Incidence trends of invasive cervical cancer in the United States by combined race and ethnicity

Objective  To better understand national patterns of invasive cervical cancer (ICC) incidence by race and ethnicity in order to develop appropriate ICC prevention policies. Methods  Age-adjusted and age-specific ICC incidence rates were calculated by combined race/ethnicity, making distinct the Hispanic/all races category from three other Non-Hispanic (White, Black and other) racial categories. Results  There was a significant downward trend in ICC incidence during both time periods for every combination of race/ethnicity (p-value <0.05) except Hispanic/all races during 1995–1999. Non-Hispanic/Black and Hispanic/all races women had significantly higher incidence rates of ICC compared to Non-Hispanic/White women. ICC incidence peaked much earlier for Non-Hispanic/White women (35–44 years of age) compared to any other racial/ethnic group. Non-Hispanic (White, Black and other) women had lower rates of adenocarcinoma and squamous cell carcinoma compared to Hispanic/all races women. Non-Hispanic/Black and Hispanic/all races women were more likely to be diagnosed at late stage or unstaged at diagnosis than Non-Hispanic/White women. Conclusion  Although ICC incidence decreased significantly over the last 10 years, Black or Hispanic US populations continue to have the highest ICC incidence compared to Non-Hispanic/Whites, highlighting the need for improved health literacy and social support to ensure their equal access to ICC screening and HPV prevention including HPV vaccination.     

Human papillomavirus vaccine and cervical cancer prevention

Cervical cancer is one of the most common types of cancer in women worldwide, with the highest rates observed in underdeveloped countries. In the last decades, its incidence has decreased after the implementation of screening programs, mainly in developed countries. Iinfection with high-risk oncogenic HPV is associated with precancerous lesions and cervical cancer. Advances in the understanding of the role of HPV in the etiology of high-grade cervical lesions (CIN 2/3) and cervical cancer have led to the development, evaluation and recomendation of two prophylactic HPV vaccines. This review article provides a summary of the studies related with their development and efficacy.     

Cervical carcinoma in Southern Mexico: Human papillomavirus and cofactors

Background: This study was conducted to determine human papillomavirus (HPV) types in women with cervical cancer (CC) and normal cervical cytology in the Southern region of Mexico, and to know the contribution of HPV types and cofactors in cervical cancer etiology. Methods: A case-control study was performed in 133 women with CC and 256 controls. HPV detection was done by MY09/11 and GP5+/GP6+ PCR systems and typing by restriction fragment length polymorphism or DNA sequencing. Results: HPV was found in 100% of CC and 35.5% of controls. The genotype distribution in CC was: HPV 16 (66.8%), 18 (9%), 31 (7.5%), 45 (4.5%), 58 (3.7%), 69 (3%), 52 (1.6%), 6, 11, 33, 56, and 67 (0.8% each). Among controls, HPV 33 followed by HPV 16 were the most frequent. Cervical cancer was associated with HPV 16 (OR = 573.5), HPV 18 (OR = 804.4), and undetermined risk HPV (types 67 and 69) (OR = 434.3). Age at first intercourse <16 years (OR = 9.6) and ≥3 births (OR = 16) were significant risk factors for CC. Conclusions: HPV 16, by far, is the most frequent type in CC, HPV 16 and 18 are responsible for 75.8% of the CC cases and high-risk HPV for 94.7%, which is useful data to take into account in vaccination programs. HPV 33 is the most frequent type in controls and high-risk HPV are more common than low-risk HPV.