机会性筛查人群中高危型人乳头瘤病毒与宫颈病变相关性的分析

目的 研究第二代杂交捕获法(HC2)高危型人乳头瘤病毒(HR-HPV)检测阳性样品中HPV与宫颈病变的相关性.方法 随机抽取HC2阳性患者602名(344名行细胞学检查),采用PCR-反向点杂交(RDB)法对HPV分型并分析HPV型别与细胞学的相关性.结果 602例患者PCR阳性率94.5%;HPV分型检出率依次为HPV16、52、58、56、39等;HC2检测谱外单独感染24例;HPV16、HPV16/18与ASCUS、LSIL、HSIL有明显相关性.结论 机会性筛查人群中最常见HPV型别依次为HPV16、52、58;HC2检测的假阳性率为4.0%;HPV16与宫颈病变程度相关.     

机会性筛查人群中高危型人乳头瘤病毒与宫颈病变相关性的分析

目的研究第二代杂交捕获法（HC2）高危型人乳头瘤病毒（HR—HPV）检测阳性样品中HPV与宫颈病变的相关性。方法随机抽取HC2阳性患者602名（344名行细胞学检查）,采用PCR一反向点杂交（RDB）法对HPV分型并分析HPV型别与细胞学的相关性。结果602例患者PCR阳性率94．5％;HPV分型检出率依次为HPVl6、52、58、56、39等;HC2检测谱外单独感染24例;HPVl6、HPVl6／18与ASCUS、LSIL、HSIL有明显相关性。结论机会性筛查人群中最常见HPV型别依次为HPVl6、52、58;HC2检测的假阳性率为4．0％;HPVl6与宫颈病变程度相关。     

宫颈细胞学筛查及高危型HPV检测与宫颈组织学改变的相关性研究

目的 探讨宫颈细胞学及高危型HPV检测结果与宫颈组织病变的相关性,提高宫颈病变早期诊断的敏感度和特异度.方法 将254例不孕患者宫颈细胞学及高危型HPV检测结果分为四组,A组:宫颈细胞学阳性、高危型HPV阳性:B组:宫颈细胞学阳性、高危型HPV阴性;C组:宫颈细胞学阴性、高危型HPV阳性;D组:宫颈细胞学阴性、高危型HPV阴性,回顾分析此四组检测数据与宫颈组织病理之间的关系;并分别回顾分析宫颈细胞学阳性及高危型HPV阳性与宫颈组织病理之间的关系,比较其敏感度和特异度.结果 A组宫颈CINⅡ级及以上的发现率显著高于B组(P＜0.01),A组、B组和C组的CIN Ⅰ级发现率无差异(P＞0.05);单一宫颈细胞学检测CINⅡ级及以上阳性的敏感度100.0％、特异度46.74％,串行高危型HPV检测后其敏感度97.22％、特异度87.16％.结论 不孕症患者乃至日常体检宫颈筛查仍首选宫颈细胞学检查,宫颈细胞学串行高危型HPV检查明显降低了宫颈病变的误诊率.     

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。     

人乳头瘤病毒检测在宫颈病变中的应用价值

Objective To detect the human papillomavirus(HPV) infectious condition in women with abnormal cytology and evaluate its values in the screening of high grade cervical intraepithelial lesion.Method 1O1 patients who underwent thinprep cell test(TCT) with abnormal cervical cytology were selected to undergo HPV test, all subjects also received tissue biopsy at the same time. Results ( 1 )Among the 101 patients,the incidence rates of high risk HPV infection of those with ASCUS, LSIL, HSIL and squamous cell carcinoma were 84. 2% ,88.6% , 100. 0% and 2/2 respectively. (2)Among the patients with abnormal cytology,the number of patients with pathologically confirmed results of CIN Ⅰ and CIN Ⅱ or worse were 20 and 81, the incidence rates of high risk HPV infection of those with CIN Ⅰ and CIN Ⅱ or worse were 60.0% and 97.5% respectively. (3) In the ASCUS group, the incidence rates of CIN Ⅱ or worse with high risk HPV infection were 87.5% and the incidence rates of CIN Ⅱ or worse without high risk HPV infection were 16.7%. (4)The prevalence of high risk HPV types from highest to lowest order were follow: HPV16 (39. 6% ) ,58( 17. 8% ) ,52 ( 16. 8% ), 18 ( 9. 9% ) ,33 ( 9.9% ). Conclusions The infection rate of high risk HPV was positively correlated with the levels of cervical lesions. HPV test is a good triage approach for the patients with ASCUS. HPV16,58,52,18,33 are the most common in the patients of cervical lesions.     

人乳头瘤病毒检测在宫颈病变中的应用价值

Objective To detect the human papillomavirus(HPV) infectious condition in women with abnormal cytology and evaluate its values in the screening of high grade cervical intraepithelial lesion.Method 1O1 patients who underwent thinprep cell test(TCT) with abnormal cervical cytology were selected to undergo HPV test, all subjects also received tissue biopsy at the same time. Results ( 1 )Among the 101 patients,the incidence rates of high risk HPV infection of those with ASCUS, LSIL, HSIL and squamous cell carcinoma were 84. 2% ,88.6% , 100. 0% and 2/2 respectively. (2)Among the patients with abnormal cytology,the number of patients with pathologically confirmed results of CIN Ⅰ and CIN Ⅱ or worse were 20 and 81, the incidence rates of high risk HPV infection of those with CIN Ⅰ and CIN Ⅱ or worse were 60.0% and 97.5% respectively. (3) In the ASCUS group, the incidence rates of CIN Ⅱ or worse with high risk HPV infection were 87.5% and the incidence rates of CIN Ⅱ or worse without high risk HPV infection were 16.7%. (4)The prevalence of high risk HPV types from highest to lowest order were follow: HPV16 (39. 6% ) ,58( 17. 8% ) ,52 ( 16. 8% ), 18 ( 9. 9% ) ,33 ( 9.9% ). Conclusions The infection rate of high risk HPV was positively correlated with the levels of cervical lesions. HPV test is a good triage approach for the patients with ASCUS. HPV16,58,52,18,33 are the most common in the patients of cervical lesions.     

高危型人乳头状瘤病毒和宫颈细胞学联合检测在诊断宫颈病变中的临床价值

目的 探讨高危型人乳头状瘤病毒(hish-risk human papillomavirus,HR-HPV)和宫颈细胞学联合检测在诊断宫颈病变中的临床价值.方法 对2004年10月至2006年12月北京大学第一医院就诊的患者进行HR-HPV检测和宫颈细胞学检查,对一项或两项结果异常者均行阴道镜下宫颈活检,并以宫颈活检结果为金标准,比较HR-HPV检测、宫颈细胞学检查、HR-HPV和宫颈细胞学联合检测对宫颈病变的诊断价值.结果 HR-HPV检测、宫颈细胞学检查及HR-HPV检测联合宫颈细胞学检查对诊断宫颈病变有不同价值.HR-HPV检测筛查CINⅡ、CINⅢ的敏感度、特异度、阳性预测值和阴性预测值分别为94.83%、31.06%、55.22%、87.02%,宫颈细胞学筛查CINⅡ、CINⅢ的敏感度、特异度、阳性预测值和阴性预测值分别为92.10%、31.06%、54.50%、81.43%,HR-HPV和宫颈细胞学联合检测筛查CINⅡ、CINⅢ的敏感度、特异度、阳性预测值和阴性预测值分别为99.65%、18.55%、61.46%、97.62%.结论 采用HR-HPV和宫颈细胞学联合检测可提高宫颈病变的检出率,并可指导临床医生对宫颈病变的治疗.     

人乳头瘤病毒16型内变异株与宫颈病变

目的 研究患宫颈上皮内瘤变（Cervical intraepithelial neoplasia,CIN）的汉族妇女中人乳头瘤病毒（Human papillomavirus,HPV）16型内变异株的类型及其在临床上的意义.方法 随机收集中日友好医院妇科门诊就诊的77例感染HPV16的汉族患者的宫颈脱落细胞DNA,用PCR法扩增HPV16型包含E6和E7基因的DNA片段并测序.通过对测序得到的E6基因序列与GenBank下载的参考株的比对,研究77例汉族患者中HPV16变异株的类型并探讨其与CIN的关系.结果 纳入研究的77例患者中,最小年龄21岁,最大年龄56岁,平均年龄36.39±6.86岁.其中,CIN Ⅱ级以下病变16例（占比20.8%）,CIN Ⅱ级及以上病变61例（占比79.2%）.HPV16型内变异株只有亚洲株和欧洲株两种,亚洲株38例,欧洲株39例.经χ^2检验,χ^2=0.0034,P〉0.05,尚不支持亚洲株与欧洲株的致癌作用不同.结论 虽然本研究未发现HPV16型亚洲株与欧洲株的致癌作用不同,但本研究发现77例汉族患者感染的HPV16型内变异株以亚洲株和欧洲株为主,故我们有理由推测,HPV16型内变异株在我国汉族妇女中的分布以亚洲株和欧洲株为主,而其他变异株,特别是高致癌的亚美株并不常见.     

潮州地区高危型人乳头瘤病毒载量与宫颈病变的关系

目的探讨高危型人乳头瘤病毒(high risk human papillomavirus,HR-HPV)载量与宫颈病变级别之间的关系。方法采用RT-PCR对农村35～60岁女性进行HR-HPV DNA定量检测并记录CT值,2 731例阳性者再进行核酸分子快速导流杂交分型技术(HybriMax)和液基薄层细胞学(thinprep liquid-based cytologic test,LCT)检查;对低级别鳞状上皮内病变(low grade squa-mous intraepithelial lesion,LSIL)及以上病变行阴道镜下组织病理学活检。根据LCT及病理活检结果按病变级别分成5组:无上皮内瘤变或恶性病变(non-squamous intraepithelial lesion or neoplasia,NILM)、未明确诊断意义的不典型鳞状上皮细胞(atypi-cal squamous cells of undetermined significance,ASCUS)、LSIL、高级别鳞状上皮内病变(high grade squamous intraepithelial lesion,HSIL)和鳞状细胞癌(squamous cell cacinoma,SCC)。在同级别宫颈病变中,按照HPV感染的类型分为4组:HPV52、HPV16、HPV58和多重HPV感染。采用方差分析的方法对各组平均CT值进行统计分析。结果随宫颈病变级别的升高,CT均值降低,5组CT均值间差异均具有显著性(P<0.05)。在同级别宫颈病变中,NILM组HPV58和多重HPV差异有显著性(P<0.05),ASCUS组HPV16和多重HPV差异有显著性,其余病变级别各HPV感染组间差异均无显著性(P>0.05)。结论 HR-HPV载量与宫颈病变级别呈正相关,高HR-HPV载量是影响宫颈病变级别的危险因素。     

人乳头瘤病毒分型与宫颈病变关系的研究

目的探讨不同砸别人乳头瘤病毒（Human papilloma virus,HPV）感染与宫颈疾病发生发展的关系。方法应用核酸分子快速杂交基因分型技术,对375例宫颈病变患者（宫颈炎182例、CINI81例、CINⅡ68例、CINⅢ69例、宫颈癌15例）进行HPV感染基因型分型测定,同时进行宫颈细胞学检查。结果375例标本中HPV阳性检出率为35．2％,HPV在各类宫颈病变组的阳性枪出率分别为宫颈炎18．6％,CINI32．1％,CINⅡ57．3％,CINⅢ68．9％,宫颈癌86．7％,宫颈炎组和宫颈癌病变组HPV之间结果差异有统计学意义（x^2=105．0,P〈0．05）。HPV多重感染率为32．6％,其中最常见HPV感染亚型为HPV16。结论宫颈病变严重程度与感染HPV亚型的致病能力密切相关。HPV核酸分型检测对宫颈疾病诊断和治疗具有重要意义。     

Detection of high risk human papillomavirus in routine cervical smears: strategy for screening.

AIM: To develop a methodology for direct detection of high risk human papillomavirus (HPV) infection in routine cervical smears by non-isotopic in situ hybridisation (NISH) which can be compared with cytopathological assessment of the same cells. METHODS: The methodology was established using cultured cells and routine cervical smears hybridised with digoxigenin labelled probes for HPV, 16, 18, 31, and 33. The technique was applied to the analysis of 53 patients from a sexually transmitted disease clinic. RESULTS: The optimal sensitivity achieved for single HPV detection in cultured cells was 1-2 copies of HPV 16 per cell and that for detection of a cocktail of HPV types in routine cervical smears was 2.5-12 copies per cell. Of parallel smears taken from patients with a normal Papinacolau-stained smear 33.3% (24) contained a HPV 16, 18, 31, and 33 signal indicating an occult HPV infection. The prevalence of these HPV types was similar in women in whom a cytopathological diagnosis of wart virus infection was made (64.7%, 17) and in patients with mild dyskaryosis (75%, 12). CONCLUSIONS: The methodology evolved localises HPV sequences directly to epithelial cell nuclei, which can be morphologically assessed by haematoxylin counterstaining. Sample contamination with exogenous viral sequences can be distinguished from true infection. In this study, a HPV signal was not found in morphologically normal epithelial cells. The methods described will permit the detection of HPV sequences in routinely collected cervical smears and the evaluation of the natural history and potential clinical relevance of HPV infection without changes in clinical practice.     

Detection and genotyping of human papillomavirus in cervical samples from Italian patients

Human papillomaviruses (HPVs) are etiological agents of cervical cancer. In order to assess the epidemiological incidence and frequency of different HPV types, we applied a polymerase chain reaction (PCR)-direct sequencing approach based on the use of MY09/MY11 primers as compared to Hybrid Capture assay. Cervical samples were taken from 1,500 women, both with normal and abnormal cytological smears, and we found an incidence of 6.6% of HPV infection in Brescia. Overall, 97 samples tested HPV-positive, yielding 18 HPV types. The four most frequent HPV types were: HPV 16, -31, -6, and -58. This approach could be used in ordinary laboratory settings for quick and reliable typing of known and novel HPVs from clinical specimens and it could also be applied to anti-cancer vaccine development.     

Association between high risk human papillomavirus infection and co-infection with Candida spp. and Trichomonas vaginalis in women with cervical premalignant and malignant lesions

BackgroundHuman papillomavirus (HPV) is the necessary cause of cervical cancer. Cervico-vaginal infection with pathogens like Chlamydia is a likely cofactor. The interactions between HPV, Trichomonas vaginalis (TV) and Candida spp. are less understood, though inflammation induced by these pathogens has been demonstrated to facilitate oncogenesis.ObjectiveOur study aimed to evaluate the association between Candida spp. and TV co-infection with HPV in cervical oncogenesis.Study designWomen with normal cervix who were high-risk HPV-negative (N = 104) and HPV-positive (N = 105); women with CIN 1 (N = 106) and CIN 2/CIN 3 (N = 62) were recruited from a community based cervical cancer screening program. Cervical cancer patients (N = 106) were recruited from a tertiary care oncology clinic. High-risk HPV was detected by Hybrid Capture II technique; Candida spp. and TV were detected by culturing the high vaginal swabs followed by microscopic examination in all. The disease status was established by histopathology in all the women.ResultHPV-positive women had significantly higher risk of having precursor lesions (of any grade) and cancer compared to HPV-negative women. Candida spp. or TV infection did not alter the risk of low grade or high grade lesions among HPV- positive women. HPV positive women co-infected with TV had higher risk of cervical cancer but not those co-infected with Candida spp.ConclusionThe higher risk of cancer observed in the women co-infected with HPV and TV without any enhanced risk of CIN 3 suggests secondary infection of the malignant growth by TV rather than any causal role. Co-infection with Candida spp. and/or TV infection did not increase the carcinogenic effect of HPV on cervix.     

DNA倍体定量分析联合HR-HPV检测在宫颈病变中的应用价值

目的：探讨DNA倍体定量分析联合高危型人乳头瘤病毒(high risk human papillomavirus,HR-HPV)检测技术在宫颈病变诊断中的应用价值。方法：对94例具有明确病理诊断结果的宫颈病变患者行DNA倍体定量和HR-HPV检测数据分析,分别计算单独和联合检测DNA异倍体、HR-HPV感染预测高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)及以上病变的灵敏度、特异度、阳性预测值、阴性预测值和诊断符合率,绘制相应的ROC曲线;分析DNA倍体定量的结果与HR-HPV检测的结果有无相关关系;比较DNA异倍体阳性的不同宫颈病变组织中>5c和>9c细胞的个数。结果：单独和联合检测DNA异倍体、HR-HPV感染预测HSIL及以上病变的灵敏度、特异度、阳性预测值、阴性预测值、诊断符合率分别为98.03%,94.11%,92.15%、41.86%,53.48%,72.09%、66.66%,70.58%,79.66%、94.73%,88.46%,88.57%、72.34%,75.53%,82.97%。从ROC曲线下面积可以直观地看出联合检测DNA异倍体和HR-HPV感染预测HSIL及以上病变的诊断价值最高。DNA异倍体阳性和阴性、HR-HPV阳性和阴性的不同宫颈病变发生率比较,差异均有统计学意义(P<0.01)。DNA倍体分析结果与HR-HPV检测结果呈正相关趋势(rn=0.281,P<0.01)。DNA异倍体阳性的不同宫颈病变组织每1000个被测细胞中出现>5c的细胞个数,在慢性宫颈炎、低度鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)、HSIL和宫颈癌中分别为0.31±0.14、0.40±0.16、2.08±0.68、2.37±0.81;慢性宫颈炎、LSIL患者分别与HSIL、宫颈癌患者比较,差异均有统计学意义(P<0.01)。慢性宫颈炎、LSIL患者中未见>9c细胞,HSIL、宫颈癌患者中>9c细胞个数分别为1.31±0.65、1.64±0.75,差异无统计学意义(P>0.05)。结论：DNA倍体定量分析联合HR-HPV检测在宫颈病变,特别是宫颈HSIL及以上病变的筛查中具有较高的诊断价值。>9c异倍体细胞的检出很大可能提示宫颈HSIL及以上病变的存在。     

HPV高危型别检测联合细胞学检查对宫颈病变筛查的研究

目的 研究人乳头瘤病毒HPV高危型别检测联合液基薄层细胞学检查（TCT）及阴道镜检查对宫颈癌及癌前病变筛查的诊断价值。方法 对1375例宫颈组织细胞样本进行HPV高危型别检测,对其中阳性样本进行TCT检查,有宫颈上皮内瘤变者（CIN）行阴道镜下活检病理组织学确诊。HPV高危型别检测采用双色荧光定量PCR方法进行8种高危型HPV DNA（主要高危型：HPV16,18,45,31）和次要高危型（HPV33,52,58,67）分型及病毒载量检测。结果 1375例样本高危型HPV DNA检测结果为阳性256例,阳性率为18.62％;TCT结果为WNL的样本高危型HPV的感染率为16.41％ （42/256）;TCT结果为ASCUS以上的样本高危型HPV的感染率为83.59％（ 214/256）。HPV各型别的病毒载量在TCT结果为WNL、ASCUS及LSIL/HSIL/SCC之间差异无统计学意义（P＞0.5）。TCT与阴道镜的阳性符合率分别为WNL-正常或炎症92.86％（ 39/42）,LISL-CIN I 81.36％（48/59）,HSIL-CIN Ⅱ＆Ⅲ 85.19％ （23/27）,SCC-宫颈癌9/10。结论 HPV高危型别检测联合TCT技术及阴道镜检查能显著提高宫颈病变的阳性检出率,可作为宫颈癌及宫颈上皮内瘤变（ CIN）筛查的可靠早期诊断方法,具有重要临床应用价值。     

Practice patterns in cervical cancer screening and human papillomavirus testing

The use of human papillomavirus DNA testing plus Papanicolaou (Pap) testing (cotesting) for cervical cancer screening in women 30 years and older has been recommended since 2006. However, few studies have detailed the adoption of such cotesting in clinical practice. We examined the trends in monthly percentage of Pap tests ordered as cotests in our laboratory over a 2.5-year period and used joinpoint regression to identify periods in which there was a change in the average monthly proportion of cotests. Cotesting of patients 30 years and older increased from 15.9% in January 2008 to 39.4% in June 2010. In patients aged 18 to 29 years, cotesting initially increased, but showed a downward trend in the last 14 months of the study, ending at 7.7% in June 2010. Our study highlights increased adoption of age-appropriate cotesting as well as the persistence of age-inappropriate cotesting.     

Preferential sites for the integration and disruption of human papillomavirus 16 in cervical lesions

BackgroundPersistent infection with high-risk human papillomavirus (HPV) is necessary to cause cervical cancer, and integrating viral DNA into the host genome may contribute to the process of carcinogenesis. The underlying mechanisms are still unclear.ObjectiveIn this study, we aimed to investigate the distribution of HPV 16 integration in the host genome and disrupted sites in the viral genome.Study designThe physical status of HPV 16 genomes in 46 cervical precancerous and cancerous lesions was determined via ligation-mediated chain reaction (DIPS) using 15 previously published primer sets and 12 newly designed primer sets.ResultsA total of 60 viral-cellular junctions were identified in 31 of 46 specimens, and over 80% of the integration sites in the human genome were located in regions of repetitive elements. The proportion of LSIL-, HSIL-, and SCC-containing integration sites near cancer-relevant genes was 10%, 18.8%, and 33.3%, respectively. The frequency of viral gene disruption was significantly higher (P < 0.05) in the L2 gene than in other regions of the viral genome.ConclusionThere are sites of preferential HPV 16 integration. The integration sites tend to be located in repetitive regions of the host genome, and some sites are found near cancer-relevant genes. In addition, the HPV 16 genome is more likely to be disrupted in the L2 gene locus.