宫颈疾病筛查项目在妇科专项体检中的应用状况

 目的 调查宫颈疾病筛查项目在常规体检中的应用状况。方法 回顾分析2010年1月1日至2011年12月31日复旦大学附属妇产科医院体检中心所有参加体检的24 135例次资料,调查其宫颈疾病筛查项目状况,包括巴氏涂片检查(Papanicolaou smear,Pap)、液基细胞学检测(thinprep cytology test,TCT)、人乳头瘤病毒(human papillomavirus,HPV)检测及联合检测(HPV+Pap或HPV+TCT)的应用情况,同时计算HPV检测人群中病毒负荷量的分布情况。结果 行Pap检查者12 967例次(53.7%),TCT检测者9 516例次(39.4%),HPV检测者5 517例次(22.9%),联合检测共计5 461例次(22.7%)。宫颈异常阳性检出率TCT高于Pap (χ2=3.866,P=0.049)。分层分析表明,HPV+Pap或HPV+TCT的联合检测法均显著优于单纯Pap或TCT检测(χ2=419.954, P=0.000;χ2=588.001,P=0.000),提示HPV检测的重要性。结论 妇科专项体检中宫颈疾病筛查方法传统,HPV检测和联合检测应用率偏低,应引起重视。同时,对于HPV负荷量≤100 RLU/CO的高危人群宜跟踪随访,以早期发现病变、降低宫颈癌发病风险。     

Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results

CONTEXT: A Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results. OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing. DESIGN AND SETTING: Natural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996. PARTICIPANTS: From a cohort of 46009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified. MAIN OUTCOME MEASURES: Cervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology. RESULTS: Of 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1 % (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%). CONCLUSIONS: For women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.     

高危型人乳头瘤病毒检测在子宫颈病变筛查和处理中的意义及作用

人乳头瘤病毒(HPV)感染是子宫颈癌发生的必要因素,HPV检测可最大程度优化子宫颈筛查和子宫颈异常细胞学的临床处理。对于30岁以上妇女,如HPV检测为阴性且子宫颈细胞学检查正常,可安全地将子宫颈筛查间隔延长至3年。但是,由于HPV病毒感染在年轻妇女中常见且多为一过性感染,因此不建议将HPV检测作为年龄小于30岁妇女的子宫颈筛查内容。对于任何年龄妇女,建议将HPV检测作为未明确诊断的不典型鳞状上皮细胞患者的分流检测方法,同时对于不能除外高度鳞状上皮内病变的不典型鳞状上皮细胞、鳞状上皮内低度病变或不典型腺细胞而未发现中或重度不典型增生的患者,HPV也是随诊方法之一。对于治疗后患者,HPV检测也和阴道镜及子宫颈细胞学一样,可作为随诊方法。HPV检测的正确使用可促进异常子宫颈细胞学的处理。     

不典型鳞状细胞和低度鳞状上皮内病变中高危型人乳头瘤状病毒检测的作用

目的:探讨高危型人乳头瘤状病毒(human papillomavirus , HPV)检测对宫颈液基细胞学诊断为不能明确意义的不典型鳞状细胞(atypical squamous cells undetermined significance, ASC-US)和低度鳞状上皮内病变(low squamous intraepithelial lesion , LSIL)的分流管理作用.方法:对940例宫颈液基细胞学检查结果为ASC-US或LSIL的患者采用二代杂交捕获(hybird capture Ⅱ, HC-Ⅱ)方法检测高危型HPV DNA,并在阴道镜指导下进行宫颈活检.结果:940例中,ASC-US 497例,LSIL 443例.行宫颈活检病理诊断,慢性宫颈炎417例,宫颈湿疣315例,宫颈上皮内瘤变(cervical intraepithelial lesions, CIN)1级124例,CIN2 级65例,CIN3级或宫颈浸润癌19例.在宫颈细胞学异常的ASC-US和LSIL组中,高危型HPV阳性率分别是59.6%和84.9%.在ASC-US和LSIL组HPV阴性时CIN2级及其以上病变(CIN2级,CIN3级或宫颈浸润癌)检出率为0.5%和6.0%,HPV阳性时检出率是8.8%和14.1%,HPV阳性时CIN2级及其以上病变检出率高于HPV阴性患者,差异具有统计学意义.在ASC-US组中,高危型HPV检测对CIN2级及其以上病变的阴性预测值达99.5%;当高危型HPV DNA检测结果在1～9.99时,CIN2级及其以上病变仅占1.6%;在10以上时,CIN2级及其以上病变占10.7%.结论:宫颈细胞学为ASC-US的患者如果高危型HPV阳性,检出CIN2级及其以上病变的概率增加,并且高危型HPV检测的阴性预测值高,在ASC-US患者中,随着HPV载量增高,检出CIN2级及其以上病变的概率随之增高.高危型HPV检测和病毒载量有助于ASC-US的分流管理,而对LSIL无分流管理作用.     

Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance

CONTEXT: Every year approximately 2 million US women are diagnosed as having a cervical cytological result of atypical squamous cells of undetermined significance (ASC-US). OBJECTIVE: To determine the most efficient and cost-effective management strategy for women in the United States diagnosed as having ASC-US. DESIGN AND SETTING: Cost-effectiveness analysis of data from clinical trials, prospective studies, and other published literature. A computer-based model was used to compare 4 management strategies for a cytological result of ASC-US: immediate colposcopy; human papillomavirus (HPV) triage, which includes colposcopy if high-risk HPV types are detected; repeat cytology, which includes follow-up cytology at 6 and 12 months and referral for colposcopy if a repeat abnormal result occurs; and reclassifying ASC-US as normal in which a cytological result of ASC-US is ignored. Reflex HPV DNA testing uses either residual liquid-based cytological specimens or samples co-collected at the time of the initial screening for conventional cytology. Another method, referred to as the 2-visit HPV DNA triage, requires a woman with an ASC-US result to return within 1 month to provide another speciman sample. MAIN OUTCOME MEASURES: Years of life saved (YLS), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS: The least costly strategy for biennial screening was to reclassify ASC-US as normal, resulting in a reduction in total cancer incidence of 75% for conventional cytology and 84% for liquid-based cytology compared with no screening. The next least costly strategy was HPV DNA testing resulting in a reduction in total cancer incidence of 86% for conventional cytology and 90% for liquid-based cytology, followed by immediate colposcopy with a reduction of 87% and 91%, respectively. Compared with reflex HPV DNA testing, a strategy of repeat cervical cytology or delayed HPV testing costs more but is less effective. When all strategies were compared simultaneously, varying frequency and type of cytological test, biennial (vs every 3 years) liquid-based cytology with reflex HPV testing had a cost of $174 200 per YLS. In a similar comparison, liquid-based cytology with reflex HPV testing conducted every 3 years (vs every 5 years) had a cost of $59 600 per YLS and was more effective and less costly than a strategy of conventional cytology incorporating repeat cytology or immediate colposcopy conducted biennially. CONCLUSION: Reflex HPV DNA testing provides the same or greater life expectancy benefits and is more cost-effective than other management strategies for women diagnosed as having ASC-US.     

HPV DNA检测在宫颈细胞学不典型腺细胞中的作用

目的 探讨高危型人乳头瘤病毒检测(HPV DNA test)和组织病理学诊断在宫颈细胞学的结果为不典型腺上皮细胞(AGC)中的关系及临床意义.方法 选择2007年1月至2009年12月北京朝阳医院阴道镜门诊就诊的97例宫颈细胞学AGC患者,分析其宫颈活检、分段诊刮、宫颈LEEP术的组织病理结果及HR HPV DNA检测的结果.结果 (1)65例(67.01%)病理异常:2例腺癌;63例(96.92%)宫颈鳞状上皮内瘤变(CIN)中40例LSIL、17例HSIL、6例鳞癌.(2)97例行HRHPV检测,其中阳性39例.在高度病变17例及宫颈癌8例中,HR-HPV检测阳性24例,其敏感性96%,特异性92.86%,阳性预测值96%,阴性预测值92.86%.(3)97例中6例行子宫全切,手术后病理检查无异常发现.1例CIN1者失访,90/91例完成随访,随访率98.9%.第1次随访6例HRHPV检测阳性及3例细胞学异常者,于第2次随访时细胞学及HR HPV检测均阴性.结论 细胞学AGC的患者给予HR HPV检测以及立即的阴道镜检查,对正确诊断、及时治疗和因其较高的阴性预测值而对临床减少过度治疗、随访管理有重要的作用.

Abstract：

Objective To evaluate the potential link between high-risk human papilloma virus (HPV) DNA testing and histological diagnosis in women referred for atypical glandular cells ( AGC) at Pap smear. Methods All cervical cytological examinations with the diagnosis of AGC between January 2007 and Dec 2009 were identified by means of a computerized database in 97 patients. The histopathological results of cervix were analyzed by colposcopic biopsy, dilatation and curettage ( D&C), cervical loop electrosurgical excision procedure(LEEP) and high-risk human papilloma virus DNA testing. Results ( 1 ) All patient were monitored by colposcopy, histopathology and HPV DNA test. Sixty-four patients had pathologic lesions. (2)In predicting the presence of high-grade of cervical intraepithelial neoplasia, the sensitivity of human papilloma virus was 96%, specificity 92. 86%, positive predictive value 96% and negative predictive value 92. 86%. (3)98. 9% of the AGC patients received colposcopic, cytological examinations and HPV test at follow-ups: 3 cases of PAP smear and 6 cases of HPV testing were abnormal at the first follow-up, and 100% negative for cytological examination and HPV test at the second follow-up visit. Conclusion HPV DNA test and colposcopic examination are effective in the initial evaluation and subsequent follow-ups of cytological atypical glandular cells.     

Benefits and costs of using HPV testing to screen for cervical cancer

CONTEXT: Despite quality assurance standards, Papanicolaou (Pap) test characteristics remain less than optimal. OBJECTIVE: To compare the societal costs and benefits of human papillomavirus (HPV) testing, Pap testing, and their combination to screen for cervical cancer. DESIGN, SETTING, AND POPULATION: A simulation model of neoplasia natural history was used to estimate the societal costs and quality-adjusted life expectancy associated with 18 different general population screening strategies: Pap plus HPV testing, Pap testing alone, and HPV testing alone every 2 or 3 years among hypothetical longitudinal cohorts of US women beginning at age 20 years and continuing to 65 years, 75 years, or death. MAIN OUTCOME MEASURE: Discounted costs per quality-adjusted life-year (QALY) saved of each screening strategy. RESULTS: Maximal savings in lives were achieved by screening every 2 years until death with combined HPV and Pap testing at an incremental cost of $76 183 per QALY compared with Pap testing alone every 2 years. Stopping biennial screening with HPV and Pap testing at age 75 years captures 97.8% of the benefits of lifetime screening at a cost of $70 347 per QALY. Combined biennial HPV and Pap testing to age 65 years captures 86.6% of the benefits achievable by continuing to screen until age 75 years. Human papillomavirus screening alone was equally effective as Pap testing alone at any given screening interval or age of screening cessation but was more costly and therefore was dominated. In sensitivity analyses, HPV testing would be more effective and less costly than Pap testing at a cost threshold of $5 for an HPV test. CONCLUSIONS: Screening with HPV plus Pap tests every 2 years appears to save additional years of life at reasonable costs compared with Pap testing alone. Applying age limits to screening is a viable option to maintain benefits while reducing costs.     

北京地区已婚妇女宫颈病变相关因素分析

目的 掌握北京地区已婚妇女宫颈病变(CIN)的发病特点及相关影响因素.方法 采用横断面调杏方法,于2007年3月至2008年9月对北京地区12个区县共137个社区内随机抽取25～54岁已婚育龄妇女6339例,进行问卷调查,妇科检查,宫颈涂片液基细胞学检测、宫颈分泌物高危型人乳头瘤病毒(HR-HPV)检测,并对宫颈细胞学异常者行阴道镜检查及活检.结果 (1)6339例调查对象,宫颈病变患者374例,患病率为5.9%;(2)在细胞学阳性的调查者中,随着细胞学异常级别的升高,宫颈病变发生率也升高;(3)30～34岁是北京地区宫颈病变的发病高峰年龄,尤其是高度病变的发病高峰;(4)HR-HPV感染率9.9%,细胞学检查阳性者HR-HPV感染率为41.2%,明显高于细胞学阴性者的感染率6.6%;(5)HR-HPV感染率随宫颈病变级别升高而提高,HR-HPV负荷量也呈逐渐增高趋势.结论 30～34岁为北京地区已婚妇女宫颈病变的高发年龄,HR-HPV感染是其患病的独立风险因素.宫颈细胞学检查可以早期提示宫颈病变的发生.应通过对已婚妇女的联合筛查及时发现宫颈病变,及时治疗,阻断宫颈癌的发生.     

宫颈液基薄层脱落细胞联合HPV及p16检测在宫颈癌早期筛查中的临床意义

目的：探讨薄层液基脱落细胞检查（TCT）、高危型乳头状瘤病毒（HPV）DNA检测及脱落细胞p16蛋白免疫细胞化学检测在宫颈癌早期筛查中的应用价值。方法对TCT、HC2- HPV- DNA检测至少一项异常的815例患者,利用剩余细胞学标本进行p16免疫组化检测,同时行阴道镜及病理组织学检查进行对照。结果 HC2- HPV- DNA的阳性率和宫颈脱落细胞中p16表达阳性率随着宫颈病变严重程度的增加而明显升高（P＜0.01）。HC2- HPV- DNA＋TCT检测提高了宫颈癌及癌前病变的检出率,p16免疫细胞化学检查则提高了检测的特异度。结论在TCT和HC2- HPV- DNA检测的基础上,联合应用脱落细胞p16免疫细胞化学染色,可提高宫颈癌早期筛查的准确性。     

液基细胞学联合高危型HPV-DNA检测筛查宫颈病变的意义

目的:探讨液基细胞学(TCT)联合高危型HPV-DNA检测在宫颈病变筛查的价值。方法:采用TCT和高危型HPV-DNA筛查宫颈病变,并在TCT基础上对ASC进行高危型HPV-DNA检测,以病理诊断为金标准,比较单独TCT检测与联合检测对诊断宫颈病变的符合率。结果:联合检测能降低假阴性率,提高敏感度和阳性预测值。结论:TCT联合HPV-DNA检测能提高宫颈病变的检出率。     

五种检测方法在宫颈癌及其前期病变筛查中的准确性评估

目的 比较5种现行的筛查方法在宫颈癌高发地区的应用,从而评价出最佳宫颈癌筛查方案,进而在浙江省范围内推广.方法 在浙江省丽水市某社区内计划选取1005名年龄在25～65岁、有性生活的女性进行宫颈癌筛查,筛查手段选择巴氏涂片、液基细胞学、HPV-DNA检测法、肉眼观察辅以醋酸白染色(VIA)和肉眼观察辅以Lugol's碘染色(VILI)5种.所有筛查者均接受阴道镜检查,以病理组织学结果为金标准,阴道镜检查无异常作为阴性结果.结果 巴氏涂片对宫颈上皮内高度病变的敏感度、特异度、阳性预测值、阴性预测值分别如下:25%,90%,26.7%,98.6%;液基细胞学的上述指标分别为81.3%,97.3%,35.1%,99.6%;VIA上述指标为:68.9%,82.8%,7.1%,99.3%;VILI上述指标分别为:81.3%,84.6%,9.1%,99.6%;HPV-DNA检测法上述指标为:87.5%,77.3%,6.8%,99.7%.结论 液基细胞学的诊断价值好于其余4种方法,可作为宫颈癌筛查的首选方法;肉眼观察由于其简单易行,价格低廉,可适用于经济欠发达地区的普通人群的筛查.

Abstract：

Objective To evaluate five screening methods of cervical cancer so as to popularize an effective screening strategy for cervical cancer in Zhejiang province. Methods A total of 1005 women aged 25 -65 years old were selected from Lishui where cervical cancer was highly prevalent. And 859 subjects were ultimately enrolled between June 2009 and December 2009. Each subject was subjected to five screening methods, including Pap smear, liquid-based cytology (LBC), human papillomavirus DNA with a second-generation hybridization assay( HC2 ), visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI). CIN (cervical intraepithelial neoplasia) 2 + on biopsy was used as the reference standard for disease positivity. Negative colposcopy was accepted as a negative outcome. Results The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV)were 25%, 90%, 26.7% and 98.6% for Pap smear; 81.3%, 97.3%, 35. 1% and 99.6% for LBC;68.9%, 82. 8%, 7. 1% and 99. 3% for VIA; 81.3%, 84. 6%, 9. 1% and 99.3% for VILI; 87. 5%,77.3% and 6. 8% for HPV-DNA test respectively. Conclusions LBC is associated with a better profile of sensitivity, specificity and predictive value for five screening methods. It has the potential of optimizing the effectiveness of primary cervical cancer screening. Due to a low cost and an easy operation, VIA screening is an effective method of screening cervical cancer in the underdeveloped areas.     

Human papillomavirus screening and cervical cancer prevention

Infection with one of several types of human papillomavirus (HPV) appears to be a necessary first step in the development of invasive cervical cancer. We cannot currently treat HPV infections; thus, the role of HPV testing is to identify women with precancerous lesions that can be removed and, in so doing, prevent progression to invasive carcinoma. Although HPV testing may help to identify women at risk of cervical cancer who might be missed by other screening tests, it is inherently nonspecific at identifying those who would otherwise develop cervical cancer. In order to avoid overtreatment of women with minor lesions with little potential for progression, HPV testing needs to be repeated or combined with Pap smears. Protocols for HPV screening have yet to be properly evaluated. Here we consider several possible applications of HPV testing in the prevention of cervical cancer. The most immediate role is as a secondary test in women with minor cytological abnormalities. Appropriate use of HPV testing as a primary screening tool depends on the setting. In a developed country without an organized screening program, HPV testing might be used in addition to Pap smears in women age 35 and over to increase sensitivity. Within an organized screening program, HPV testing might be used in combination with Pap testing, but with extended screening intervals so as to obtain the maximum advantage to women without unduly increasing costs. Where resources are strictly limited, an attractive option would be to perform visual inspection of the cervix after application of dilute acetic acid using a low threshold for referral, and to test for HPV only on those with abnormal looking lesions.     

宫颈脱落细胞学阴性生殖道高危型人乳头瘤病毒阳性患者的临床病理特征

目的 探讨宫颈脱落细胞学阴性（pap smear negative,Pap-）、人乳头瘤病毒阳性（high risk human papilloma virus positive,HPV+）女性的临床病理特征。方法 纳入1 128例Pap-/HPV+女性,阴道镜下可疑部位活检。分析Pap-/HPV+状态下HPV的流行病学特征及宫颈病变的临床病理特征。结果 Pap-/HPV+女性HPV的流行特征,HPV-16所占比例较高（χ²=16.81,P=0.000）,患者年龄偏大（χ²=20.72,P=0.000）,单一病毒感染比例较高（χ²=8.93,P=0.01）。506例患者接受阴道镜下活检,高度鳞状上皮病变（high grade squamous intraepithelial lesion,HSIL）病例254例（50.19%）,其中7例宫颈浸润癌。HSIL的发生率与年龄有关,年轻患者HSIL比例更高,与年龄呈负相关（r=-0.254,P=0.000）。各HPV亚型发生HSIL的比例不同,HPV-16型发生HSIL的比例最高（64.7%）。与对照组比较,Pap-/HPV+女性感染HPV-16、18、31、33、52、58型显著增加HSIL病变的危险。结论 Pap-/HPV+女性HPV的流行病学特征不同,具有宫颈高级别病变的危险。     

高危型人乳头瘤病毒检测在子宫颈细胞学异常者中的应用价值

目的了解子宫颈细胞学异常者中高危型人乳头瘤病毒(HPV)的感染状况,评估高危型HPV检测对细胞学异常者子宫颈高度病变的筛查效力。方法采用第二代杂交捕获实验(hc2)检测949例子宫颈超柏氏薄层液基细胞学(LCT)异常者[2001年伯塞斯达系统诊断≥未明确诊断意义的不典型鳞状细胞(ASC-US)]的高危型HPV感染状况,所有患者均同时进行组织病理学检查。结果在949例LCT异常者中,不典型鳞状上皮细胞(ASC)者432例,鳞状上皮内低度病变(LSIL)者310例,鳞状上皮内高度病变(HSIL)者207例,其高危型HPV感染阳性率分别为40.3%、44.8%和89.4%;病理学诊断无上皮内病变或恶性病变(NILM)者335例,子宫颈上皮内瘤变1、2、3级(CIN1、CIN2、CIN3)者分别为388、118和101例,子宫颈鳞状细胞癌(SCC)者7例,其高危型HPV感染阳性率分别为17.3%、66.2%、92.4%、97.0%和100%;在ASC-US组中,子宫颈高度病变在高危型HPV阳性组和阴性组的发生率分别为10.2%和0.8%,差异有显著性(P<0.01);在对子宫颈高度病变的筛查中,细胞学[≥不能除外HSIL的ASC(ASC-H)]和细胞学(≥ASC-H)联合高危型HPV检测的敏感性分别为0.925和0.991,特异性分别为0.510和0.748,两组相比差异有显著性(P<0.01);细胞学(≥LSIL)和细胞学(≥LSIL)联合高危型HPV检测的敏感性分别为0.898和0.982,特异性分别为0.567和0.779,差异有显著性(P<0.01)。结论随着子宫颈病变级别及组织病理学级别的升高,高危型HPV感染的阳性率呈上升趋势,对子宫颈细胞学异常者进行高危型HPV检测可提高筛查子宫颈高度病变的效力。     

人乳头瘤病毒检测在宫颈癌筛查中的作用

目的探讨人乳头瘤病毒(HPV)在宫颈癌筛查中的作用。方法用薄层液基细胞涂片法进行宫颈细胞学检查,对细胞学异常患者采用第二代杂交捕获试验检测高危型HPV DNA。 HPVDNA检测阳性和细胞学检测结果为非典型鳞状细胞或低度鳞状上皮内病变(LISL)以上患者,均行阴道镜下活组织病理检查。分析HPV感染与宫颈上皮内瘤变的关系。结果HPV DNA检出率随宫颈病变程度加重呈上升趋势。非典型鳞状细胞者中HPV检测阳性为31.4％,HPV阳性的非典型鳞状细胞患者中51.1％为宫颈上皮内瘤变或更严重病变。结论HPV DNA检测在宫颈癌筛查中可作为细胞学的辅助手段提高诊断准确性,减少细胞学结果为轻度异常患者不必要的阴道镜检查。高危型HPV检测可指导早期HPV感染者的治疗及用于惠者的追踪随访。     

应用基因芯片技术检测高危型人乳头瘤病毒在宫颈癌筛查中的评价

目的 评价人乳头瘤病毒（HPV）分型基因芯片检测技术在子宫颈癌筛查中的临床价值。方法 2004年11月至2004年12月，在深圳南山区华侨城社区内15～59岁有性生活妇女中进行以人群为基础的横断面调查研究。对所有筛查妇女宫颈脱落细胞采用第二代杂交捕获技术（HC2）和基因芯片技术进行高危型HPV的检测，同时以液基细胞薄层涂片技术（1ET）行宫颈细胞学检查。对HPV阳性并且LCT≥未明确诊断意义的不典型鳞状上皮细胞（ASCUS）或HPV阴性但LCT≥低度鳞状上皮内瘤样病变（LSIL）的妇女行阴道镜下活组织病理学检查，以病理结果作为验证两种HPV检测的参考标准。结果 共取组织标本122例。病理学结果证实该人群中无宫颈癌病例，子宫颈上皮内瘤样病变（CIN）Ⅲ级3例，CINⅡ级11例，CINⅠ级36例，慢性宫颈炎和鳞状上皮化生69例，正常宫颈3例。人群的HPV总检出率在HC2法为14．0％，基因芯片法为9．8％，HC2法HPV检出率明显高于基因芯片法（P〈0．001），二者一致性一般（Kappa=0．498）；随子宫颈病变级别升高，两种检测方法HPV阳性率均呈趋势性增加（P〈0．001和P〈0．005）。HC2法检测高危HPV对高度宫颈上皮内瘤样病变HSIL的灵敏度、特异度、准确性、阳性预测值、阴性预测值、阳性似然比和阴性似然比分别为100％、87．1％、87．3％、8．8％、100％、7．7和0．000；HPV分型基因芯片法以上各指标分别为78．6％、91．1％、90．9％、9．9％、99．7％、8．8和0．235。结论 第二代杂交捕获技术（HC2）高危型HPV检测仍是目前宫颈癌筛查较好的方法，基因芯片HPV分型检测除灵敏度尚需提高外，其余各指标均可与HC2法相媲美。     

第二代杂交捕获法和聚合酶链反应检测人乳头瘤病毒的比较

目的:比较两种常用的人乳头瘤病毒(HPV)的检测方法。方法:第二代杂交捕获法(HCⅡ)和聚合酶链反应(PCR)检测妇女宫颈分泌物中的高危型HPV。结果:103例宫颈病变患者中,PCR和HCⅡ检测HPV的阳性率分别为41.7％和39.9％。两种检验方法具有相关性(P<0.05)。结论:PCR和HCⅡ具有较好的一致性。     

重度宫颈上皮内瘤变进行环状电切手术治疗后病灶残余和 复发的高危因素

目的 探讨预测重度宫颈上皮内瘤变（CIN2及CIN3）进行环状电切手术（LEEP）治疗后残余病灶和疾病复发的高危因素,以及术后及早发现病变的时间点。方法 回顾性分析我院进行LEEP治疗的CIN2及CIN3共428例患者资料,治疗后用脱落细胞学和人乳头瘤病毒(HPV)杂交捕获二代（HC2）随访,以阴道镜活检为金标准判定残余和复发,据此评定其余指标的诊断价值。以logistic回归分析危险因素,κ检验验证3月和6月指标的一致性。结果 428例患者中CIN2有296例,CIN3有132例,治疗前HPV HC2 阳性率为86.7%（371/428）, 随访中26例（6.1%）有残余或者复发, LEEP切缘受累特别是锥顶阳性是疾病持续或复发的高危因素〔比值比=9.364,95%可信区间（\CI）:0.712~46.108,\P=0.001〕。其他因素如年龄（截断值40岁）、HPV负荷量(截断值100 RLU)、HPV类型（16/18 vs.其他类型）均与疾病复发无关。有残余病灶或复发的26例患者术后3月HPV HC2检测均为阳性, HPV HC2在术后3和6个月对于残余病灶的检测敏感性均为100%,均高于细胞学检测（\P\P\CI, 0.469~0.892)〕和细胞学检测结果〔κ值为0.79 (95%\CI: 0.592~0.873)〕都显示出较好的一致性。结论 LEEP手术后切缘受累特别是锥顶阳性是病灶残余或复发的危险因素。术后3月HPV检测可提供关于病灶残余或复发的及时信息。     

不同检测策略在成都双流地区宫颈癌筛查中的价值研究

目的 评估高危HPV(high-risk HPV, hr-HPV)检测和宫颈细胞学(thinprep cytology test, TCT)的不同组合策略在成都双流地区宫颈癌筛查,特别是在高级别宫颈上皮内病变筛查中的临床价值。方法 本项目为基于人群的随机临床试验。纳入符合要求的35～65岁的女性。第一年基线筛查中受试者按1∶2随机分配进行细胞学或hr-HPV检测,其中hrHPV检测呈阳性者被随机分流行细胞学或阴道镜检查。24个月后召回所有受试者,对其均进行细胞学和hr-HPV联合筛查。以上述基线筛查结果阴性且进入第三年随访并完成随访的女性为研究对象。基于上述检查结果,提取相关数据,模拟4种不同的筛查方案：(1)TCT和hr-HPV联合筛查,任一阳性则转诊阴道镜检查;(2)TCT和hr-HPV联合筛查,同时阳性则转诊阴道镜检查;(3)TCT初筛阳性者进行hr-HPV分流,hr-HPV阳性者转诊阴道镜;(4)hr-HPV初筛阳性者进行TCT分流,TCT阳性者转诊阴道镜。以组织学病检出宫颈高级别鳞状上皮内病变(HSIL⁺)为终点事件,计算不同筛查方案的敏感性、特异性、阳...     

Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity,specificity, and frequency of referral

Context  Human papillomavirus (HPV) DNA testing of women having Papanicolaou (Pap) smears showing atypical squamous cells of undetermined significance (ASCUS) has clinical usefulness. Whether HPV DNA testing alone is useful in primary screening remains to be determined. Objective  To determine the accuracy of HPV DNA testing for detecting cervical intraepithelial neoplasia (CIN) grade 3 or cancer (the criterion standard). Design, Setting, and Participants  Between December 1997 and October 2000, 4075 women who attended Planned Parenthood clinics in Washington State were screened simultaneously using thin-layer Pap and HPV DNA testing by a polymerase chain reaction (PCR)–based method and by a liquid-based RNA-DNA hybridization capture with signal amplification assay (signal amplification). Women who were positive for high-risk HPV types, or had Pap results of ASCUS or higher, were considered to have positive screening test results and were referred for colposcopy and biopsy. Additionally, a random sample of women with negative screening test results was referred for colposcopy. Based on individual and combined thin-layer Pap, HPV PCR, and HPV signal amplification test results from the screening and the colposcopy visits, 7 colposcopy triage strategies were defined and evaluated. Main Outcome Measure  Sensitivity and specificity for detecting cervical lesions graded CIN 3 or higher for each of the 7 triage strategies. Results  The estimated prevalence of CIN 3 or higher was 3.2%. The sensitivity (95% confidence interval) of thin-layer Pap (with a result of ASCUS) for identifying women with CIN 3 or higher was only 61.3% (48.5%-70.9%) compared with 88.2% (78.9%-93.8%) for HPV testing by PCR and 90.8% (83.1%-95.8%) by signal amplification. Differences in specificities were also observed: 82.4% (81.8%-83.1%) for thin-layer Pap (with a result of ASCUS), 78.8% (77.9%-79.7%) for PCR, and 72.6% (69.4%-75.0%) for signal amplification. Compared with referral for colposcopy of all women with ASCUS or higher, signal amplification testing of women with ASCUS and referral of those with a positive result was about as sensitive (61.3% vs 60.3%, respectively) and significantly more specific (82.4% vs 88.9%, respectively). The strategy requiring repeat positive PCR tests on 2 visits had a sensitivity of 84.2% (75.3%-91.0%) and a specificity of 86.2% (85.1%-87.3%). All tests were more specific and less sensitive in older (30 years) vs younger women. Conclusions  Testing for HPV has higher sensitivity but lower specificity than thin-layer Pap screening. In some settings, particularly where screening intervals are long or haphazard, screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women.