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目的:评价高危型人乳头瘤病毒(highriskhumanpapillomavirus,hrHPV )载量和分型检测在中国农村地区妇女人群中预测宫颈鳞状上皮高级别病变发生的价值。方法:2012年5 月至2015年5 月以农村妇女人群为基础选取江西省兴国县、靖安县和玉山县2 257 例,年龄35~64岁纳入本前瞻性队列研究。同时采用HC- 2(hybridcapture-2)和导流杂交技术(HybriMax )两种方法分别检测hrHPV 载量和亚型,两种方法中任一亚型阳性者行阴道镜及活检检查,并将HC- 2 检测阳性结果中病毒载量< 10.0 RLU/CO认定为低病毒载量,病毒载量≥ 10.0 RLU/CO为高病毒载量。对hrHPV 结果阴性或病理诊断为CIN 1 的2 211 例妇女行24个月无干预随访。根据随访分别评价hrHPV 载量和HybriMax 分型两种检测方法预测宫颈鳞状上皮高级别病变(CINgrade2 orworse,CIN 2 +)的效果。结果:纳入基线、随访数据完整的女性共1 636 例。2 年内采用HC- 2 检测的132 例基线高病毒载量妇女中CIN 2 +的发生率为3.03%(4/ 132),其相对危险度(RR)值为42.24(95%CI 为4.76~375.2);采用HybriMax 分型检测的159 例基线分型HPV 16或18型阳性妇女中CIN 2 + 的发生率为2.51%(4/ 159),RR值为33.06(95%CI 为3.72~293.9)。 对2 年内HC- 2 检测中高病毒载量例数和HybriMax 分型检测中HPV 16/ 18型别阳性例数进行比较,CIN 2 + 的发病率差异无统计学意义(P > 0.05)。 结论:HPV高载量和HPV 16/ 18型别阳性妇女人群进展为CIN 2 + 的风险均较高。在不具有持续监测hrHPV 条件的农村地区,HC- 2 检测的病毒载量≥ 10.0 RLU/CO阈值设定,与HybriMax 分型检测HPV 16/ 18型别均对hrHPV 初筛有分流作用,并对CIN 2+ 发生有预测作用。 相似文献
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摘 要:[目的] 评估HPV16/18 DNA分型检测对宫颈未明确意义的非典型鳞状细胞(atypical squamous cells of undetermined significance,ASC-US)女性癌前病变风险预测的分层作用。[方法] 在山西省宫颈癌筛查方法研究Ⅰ队列基础上开展,该队列所有随访对象均接受了hrHPV DNA检测(hybird capture 2,HC2)、液基细胞学检查和醋酸染色肉眼观察,任一结果阳性者转诊阴道镜,必要时取活检;同时对HC2阳性者进行HPV型别检测(LiPA)。以2005年和2014年随访时检出416例ASC-US女性为研究对象计算hrHPV DNA阴性组、hrHPV DNA阳性组、HPV16/18阳性组和其他hrHPV型别阳性组的中度及以上宫颈上皮内瘤样病变(cervical intraepithelial neoplasia grade 2 or worse,CIN2+)检出率,以及HPV16/18筛查CIN2+的临床效果。以2005年随访发现的253例ASC-US为研究对象,计算以上各组的5年CIN2+累计发病风险和相对危险度。[结果] ASC-US且hrHPV阳性者中HPV16/18阳性占27.4%,其CIN2+检出率(9.7%)高于其他hrHPV型别阳性者(3.8%),但差异无统计学意义(OR= 2.7,95%CI:0.4~17.3),hrHPV阴性者中无CIN2+检出。基线hrHPV阴性组CIN2+ 5年累积发病风险为1.9%,与之相比,其他hrHPV型别阳性组、hrHPV阳性组、HPV16/18阳性组的5年发病风险逐渐增加,分别为5.3%(RR=2.7,95%CI:0.3~23.0)、8.5%(RR=4.5,95%CI:1.1~17.8)和11.8%(RR=6.2,95%CI:1.1~33.9)。与hrHPV DNA检测相比,HPV 16/18检测筛查CIN2+的灵敏度下降,特异度升高[相对灵敏度0.6(95%CI:0.3~1.2),相对特异度1.3(95%CI:1.2~1.4)]。[结论] 在ASC-US人群中利用HPV16/18分型检测筛查CIN2+,在获得较高特异度的同时会损失灵敏度;HPV16/18能有效区分ASC-US且hrHPV阳性人群的即时和长期发病风险,可用于ASC-US人群的临床分流管理。 相似文献
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目的:研究高危型人乳头状瘤病毒感染及病毒载量与宫颈病变的关系。方法:对774例研究对象采用第二代杂交捕获试验(HC—Ⅱ)进行宫颈脱落细胞的HPV-DNA定量检测。分析不同程度宫颈病变的HPV感染情况,并根据HPV病毒载量将所有检测对象分为四组,阴性(RLU/CO〈1.0)、低载量(1.0≤RLU/CO〈10)、中载量(10≤RLU/CO〈100)、高载量(RLU/CO≥100),采用非条件多项式logistic回归分析病毒载量与宫颈病变级别的关系。结果:在检测的774例研究对象中,对照组、宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅰ、CINⅡ、CINⅢ和浸润性宫颈癌患者的HPV感染率分别为21.29%、82.35%、80.00%、90.16%和86.67%。对照组高危型HPV感染率明显低于CIN和浸润性宫颈癌患者,差异有统计学意义,P〈0.01;HPV阳性者患CIN的风险是阴性者的24.96倍(95%CI:13.20~47.18),患浸润性宫颈癌的风险是HPV阴性者的24.03倍(95%CI:12.01~48.09)。在不同级别宫颈病变中,CINI组的低病毒载量患者占11.67%,高载量占41.18%,OR值为23.84(95%CI:5.96~95.33),P〈0.001;而在CINⅢ组中62.30%的患者呈高病毒载量,OR值达64.70(95%CI:25.98~161.20),P〈0.001。结论:高危型HPV感染与CIN和浸润性宫颈癌的发生密切相关;宫颈高危型HPV病毒载量是影响宫颈病变严重程度的危险因素。 相似文献
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[目的]比较cobas 4800检测和careHPV人乳头瘤病毒(human papillomavirus,HPV)检测方法用于宫颈癌筛查的有效性和一致性。[方法]本研究纳入856名研究对象,采用cobas4800和careHPV检测方法对宫颈脱落细胞标本进行HPV DNA检测。以病理组织学为金标准,评估careHPV和cobas 4800检出宫颈上皮内瘤变2(cervical intraepithelial neoplasia grade 2,CIN2)及以上病人的有效性和准确性。采用McNemar检验对两种检测方法进行一致性检验。[结果]最终853例妇女的有效检测结果纳入统计分析。careHPV和cobas 4800检出HPV DNA阳性率分别是37.1%(316/853)和39.3%(335/853)。cobas 4800检测和careHPV检出HPV DNA一致率为83.2%(710/853),Kappa=0.65(95%CI:0.59-0.70)。careHPV和cobas 4800检出CIN2+的敏感度和特异性分别为94.4%(95%CI:81.3%-99.2%)和65.5%(95%CI:62.1%-68.7%),94.4%(95%CI:81.3%-99.2%)和63.2%(95%CI:59.7%-66.5%)。在最后纳入统计分析的853名妇女中HPV16和HPV 18的感染率分别为13.1%和2.6%,而在36例CIN2+的病人中,HPV16和HPV18的感染率分别为77.8%和2.8%。[结论]careHPV和cobas4800作为初筛方法检出CIN2+的一致性较好,然而两种方法又有其不同的优势,应该根据当地的经济水平来选择用于筛查的HPV DNA检测方法。 相似文献
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目的 探讨女性宫颈高危型人乳头瘤病毒(hrHPV)感染现状并分析hrHPV病毒载量与宫颈病变之间剂量—效应关系。方法 对26294份宫颈细胞学送检标本采用杂交捕获第二代方法(HC-Ⅱ)检测HPV-DNA含量,病毒载量以相对光单位(RLU)与界值点(Cutoff)比值衡量。以RLU/CO≥1.0为阳性。宫颈病变按组织学活检以CIN2及以上级别病变为病例。假设检验采用χ2检验;用Mantel趋势分析分析剂量—效应关系。结果 26294例受检对象总体阳性检出率为26.74%,年龄分布在15~84岁之间,平均年龄为(33.54±8.43)岁。hrHPV病毒载量与宫颈病变存在剂量—效应关系(χtrend=8.000,P<0.001)。结论 广东省女性hrHPV感染阳性检出率较高;hrHPV病毒载量与宫颈病变之间存在剂量—效应关系。 相似文献
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Snijders PJ Hogewoning CJ Hesselink AT Berkhof J Voorhorst FJ Bleeker MC Meijer CJ 《International journal of cancer. Journal international du cancer》2006,119(5):1102-1107
An increased high-risk human papillomavirus (hrHPV) viral load in cervical scrapings has been proposed as a determinant for high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (> or =CIN 2), but data so far for HPV types different from HPV 16 are limited and inconsistent. In addition, a viral load threshold to distinguish hrHPV positive women without > or =CIN 2 still has not been defined. Here, we used baseline cervical scrapings of women with normal cytology participating in a large population-based cervical screening trial (i.e. POBASCAM) who were GP5+/6+-PCR positive for 4 common hrHPV types, i.e. HPV 16, 18, 31 or 33, as a reference to arbitrarily define various viral load thresholds (i.e. 25th, 33rd, 50th, 67th and 75th percentiles of the lowest viral load values) for distinguishing women having single infections with these types without high-grade CIN. Viral load assessment was performed by real time type-specific PCR. The viral load threshold values were subsequently validated on abnormal cervical scrapes of 162 women with underlying, histologically confirmed CIN lesions containing 1 of these 4 hrHPV types. All 59 women with CIN 3 had viral load levels that were higher than those of 33% of the women with normal cytology containing the respective hrHPV type detectable by GP5+/6+-PCR (i.e. higher than the 33rd percentile of viral load). By using this 33rd percentile viral load cut-off, sensitivity for CIN 3 of 100% (95% CI 93.9-100) was obtained. Hence, application of this viral load threshold would increase the specificity of HPV testing for HPV 16, 18, 31 and 33-associated prevalent CIN 3 without the cost of a marked reduction in sensitivity. In practice, on the basis of viral load analysis, a less aggressive management can be foreseen for 33% of the women with normal cytology participating in a population-based screening program who are GP5+/6+-PCR positive for HPV 16, 18, 31 or 33. 相似文献
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Annemiek Leeman Marta del Pino Lorena Marimon Aureli Torné Jaume Ordi Bram ter Harmsel Chris J.L.M. Meijer David Jenkins Folkert J. Van Kemenade Wim G.V. Quint 《International journal of cancer. Journal international du cancer》2019,144(1):160-168
Cervical screening aims to identify women with high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 2-3 (HSIL/CIN2-3) or invasive cervical cancer (ICC). Identification of women with severe premalignant lesions or ICC (CIN3+) could ensure their rapid treatment and prevent overtreatment. We investigated high-risk human papillomavirus (hrHPV) detection with genotyping and methylation of FAM19A4/miR124-2 for detection of CIN3+ in 538 women attending colposcopy for abnormal cytology. All women had an additional cytology with hrHPV testing (GP5+/6+-PCR-EIA+), genotyping (HPV16/18, HPV16/18/31/45), and methylation analysis (FAM19A4/miR124-2) and at least one biopsy. CIN3+ detection was studied overall and in women <30 (n = 171) and ≥30 years (n = 367). Positivity for both rather than just one methylation markers increased in CIN3, and all ICC was positive for both. Overall sensitivity and specificity for CIN3+ were, respectively, 90.3% (95%CI 81.3–95.2) and 31.8% (95%CI 27.7–36.1) for hrHPV, 77.8% (95%CI 66.9–85.8) and 69.3% (95%CI 65.0–73.3) for methylation biomarkers and 93.1% (95%CI 84.8–97.0) and 49.4% (95%CI 44.8–53.9) for combined HPV16/18 and/or methylation positivity. For CIN3, hrHPV was found in 90.9% (95%CI 81.6–95.8), methylation positivity in 75.8% (95%CI 64.2–84.5) and HPV16/18 and/or methylation positivity in 92.4% (95%CI 83.5–96.7). In women aged ≥30, the sensitivity of combined HPV16/18 and methylation was increased (98.2%, 95%CI 90.6–99.7) with a specificity of 46.3% (95%CI 40.8–51.9). Combination of HPV16/18 and methylation analysis was very sensitive and offered improved specificity for CIN3+, opening the possibility of rapid treatment for these women and follow-up for women with potentially regressive, less advanced, HSIL/CIN2 lesions. 相似文献
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Bulk S Bulkmans NW Berkhof J Rozendaal L Boeke AJ Verheijen RH Snijders PJ Meijer CJ 《International journal of cancer. Journal international du cancer》2007,121(2):361-367
Adding a test for high-risk human papillomavirus (hrHPV) to cytological screening enhances the detection of high-grade cervical intraepithelial neoplasia (>or=CIN2), but data are required that enable long-term evaluation of screening. We investigated the >or=CIN2 risk for women participating in population-based screening as a function of hrHPV and cytology testing results at baseline and at 6 months. We included 2,193 women aged 30-60 years participating in a population-based screening trial who received colposcopy or a repeat testing advice at baseline. The main endpoint was histologically confirmed >or=CIN2 diagnosed within 36 months. hrHPV testing was more sensitive than cytology for >or=CIN2 (relative sensitivity 1.4, 95%CI: 1.3-1.5; absolute sensitivity 94.1 and 68.0%, respectively). The 18-month >or=CIN2 risks in women with a hrHPV-positive smear and in women with abnormal cytology were similar (relative risk 0.9, 95%CI: 0.8-1.1). Women with HPV16 and/or HPV18 had a higher >or=CIN2 risk than other hrHPV-positive women irrespective of the cytological grade. Repeat testing showed that both cytological regression and viral clearance were strongly associated with a decrease in >or=CIN2 risk. Notably, women who had a double negative repeat test at 6 months had a >or=CIN2 risk of only 0.2% (95%CI: 0.0-1.1) and hrHPV-negative women with baseline borderline or mild dyskaryosis and normal cytology at 6 months had a >or=CIN2 risk of 0% (95%CI: 0.0-0.8). Using hrHPV and/or cytology testing, risk of >or=CIN2 can be assessed more accurately by repeat testing than single visit testing. Hence, when hrHPV testing is implemented, patient management with repeat testing is a promising strategy to control the number of referrals for colposcopy. 相似文献
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Long‐term risk of cervical intraepithelial neoplasia grade 3 or worse according to high‐risk human papillomavirus genotype and semi‐quantitative viral load among 33,288 women with normal cervical cytology 下载免费PDF全文
Louise T. Thomsen Kirsten Frederiksen Christian Munk Jette Junge Thomas Iftner Susanne K. Kjaer 《International journal of cancer. Journal international du cancer》2015,137(1):193-203
In this prospective cohort study, we estimated the long‐term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high‐risk human papillomavirus (hrHPV) genotype and semi‐quantitative viral load at baseline among 33,288 women aged 14–90 years with normal baseline cytology. During 2002–2005, residual liquid‐based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV‐tested with Hybrid Capture 2 (HC2) and genotyped with INNO‐LiPA. Semi‐quantitative viral load was measured by HC2 relative light units in women with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8‐year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0–25.6%). The corresponding risks for HPV18, HPV31, HPV33, and other hrHPV types, respectively, were 12.8% (95% CI: 7.6–18.0%), 11.3% (95% CI: 7.7–14.9%), 12.9% (95% CI: 7.0–18.8%) and 3.9% (95% CI: 2.7–5.2%). Similar absolute risk estimates were observed in women aged <30 years. Higher HPV16‐viral load was associated with increased risk of CIN3+ (hazard ratio = 1.34, 95% CI: 1.10–1.64, per 10‐fold increase in viral load). A similar trend, although statistically nonsignificant, was found for viral load of HPV18. The 8‐year absolute risk of CIN3+ in women with HPV16‐viral load ≥100.0 pg/ml was 30.2% (95% CI: 21.9–38.6%). Our results support that hrHPV genotyping during cervical cancer screening may help identify women at highest risk of CIN3+. 相似文献
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Comparing the performance of FAM19A4 methylation analysis,cytology and HPV16/18 genotyping for the detection of cervical (pre)cancer in high‐risk HPV‐positive women of a gynecologic outpatient population (COMETH study) 下载免费PDF全文
Johannes Berkhof Peter J.F. Snijders Maaike G. Dijkstra Margot H. Uijterwaal Renske D.M. Steenbergen Folkert J. van Kemenade Lawrence Rozendaal Theo J.M. Helmerhorst Rene H.M. Verheijen W. Abraham Ter Harmsel W. Marchien Van Baal Peppino G.C.M. Graziosi Wim G.V. Quint Daniëlle A.M. Heideman Chris J.L.M. Meijer 《International journal of cancer. Journal international du cancer》2016,138(4):992-1002
Recently, DNA methylation analysis of FAM19A4 in cervical scrapes has been shown to adequately detect high‐grade cervical intraepithelial neoplasia and cervical cancer (≥CIN3) in high‐risk HPV (hrHPV)‐positive women. Here, we compared the clinical performance of FAM19A4 methylation analysis to cytology and HPV16/18 genotyping, separately and in combination, for ≥CIN3 detection in hrHPV‐positive women participating in a prospective observational multi‐center cohort study. The study population comprised hrHPV‐positive women aged 18–66 years, visiting a gynecological outpatient clinic. From these women, cervical scrapes and colposcopy‐directed biopsies (for histological confirmation) were obtained. Cervical scrapes were analyzed for FAM19A4 gene promoter methylation, cytology and HPV16/18 genotyping. Methylation analysis was performed by quantitative methylation‐specific PCR (qMSP). Sensitivities and specificities for ≥CIN3 were compared between tests. Stratified analyses were performed for variables that potentially influence marker performance. Of all 508 hrHPV‐positive women, the sensitivities for ≥CIN3 of cytology, FAM19A4 methylation analysis, and cytology combined with HPV16/18 genotyping were 85.6, 75.6 and 92.2%, respectively, with corresponding specificities of 49.8, 71.1 and 29.4%, respectively. Both sensitivity and specificity of FAM19A4 methylation analysis were associated with age (p ≤ 0.001 each). In women ≥30 years (n = 287), ≥CIN3 sensitivity of FAM19A4 methylation analysis was 88.3% (95%CI: 80.2–96.5) which was noninferior to that of cytology [85.5% (95%CI: 76.0–94.0)], at a significantly higher specificity [62.1% (95%CI: 55.8–68.4) compared to 47.6% (95%CI: 41.1–54.1)]. In conclusion, among hrHPV‐positive women from an outpatient population aged ≥30 years, methylation analysis of FAM19A4 is an attractive marker for the identification of women with ≥CIN3. 相似文献
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Bulkmans NW Bleeker MC Berkhof J Voorhorst FJ Snijders PJ Meijer CJ 《International journal of cancer. Journal international du cancer》2005,117(2):177-181
High-risk human papillomavirus (hrHPV) types are causally related to cervical cancer and its high-grade precursor lesions. The risk posed by the different hrHPV types for the development of cervical intraepithelial neoplasia grade 2 or worse (> or =CIN2) needs to be established. Here, we present the hrHPV type-distribution in relation to cytology and histology for women participating in a cervical screening program. From 44,102 women who participated in a population-based cervical screening program in the Netherlands, 2,154 hrHPV GP5+/6+ PCR positive women were recruited to determine the distribution of 14 hrHPV types by reverse line blotting of GP5+/6+ PCR products. For each HPV type, associations with cytology and histologically confirmed > or =CIN2 were measured by odds ratios. HPV types 16 and 33 were more prevalent in women, amongst those containing a single hrHPV type, with moderate dyskaryosis or worse (>BMD) than in women with normal cytology, but only in case of underlying > or =CIN2 (OR 4.10, 95%CI 2.98-5.64 and OR 2.68, 95%CI 1.39-5.15, respectively). Similar results were obtained for women with double infections (OR 3.29, 95% CI 1.61-6.75 and OR 4.37, 95% CI 1.17-16.34). Coexisting types did not influence the prevalence of > or =CIN2 in HPV 16 or 33 positive women. The increased prevalence of type 16 and 33 in hrHPV positive women with > or =CIN2, compared to women with normal cytology, suggests that infection with these types confers an increased risk for development of > or =CIN2. Distinguishing these types may therefore have implications for future cervical screening strategies. 相似文献
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Marcela?Lagos Vanessa?Van De Wyngard Helena?Poggi Paz?Cook Paola?Viviani María?Isabel?Barriga Martha?Pruyas Catterina?Ferreccio
Background
We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants.Methods
Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test).Results
Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %.Conclusions
HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.18.
Comparison of hybrid capture 2 with in situ hybridization for the detection of high-risk human papillomavirus in liquid-based cervical samples 总被引:2,自引:0,他引:2
Hesselink AT van den Brule AJ Brink AA Berkhof J van Kemenade FJ Verheijen RH Snijders PJ 《Cancer》2004,102(1):11-18
BACKGROUND: The performance of two commercially available detection systems for high-risk HPV (hrHPV), Hybrid Capture 2 (HC2) and in situ hybridization (ISH), were compared on cervical scrapings. METHODS: Using general primer (GP)-mediated GP5+/6+-polymerase chain reaction (PCR)-enzyme immunoassay and reverse line blot genotyping, 76 liquid-based cervical samples were identified with > or = 1 of the 12 hrHPV types present in the probes of the HC2 and ISH assays. The positivity rate of the assays and the HC2 viral load were determined and related to cytologic findings (n = 76 samples) and histologic findings (n = 43 samples). RESULTS: Overall, HC2 scored significantly more samples positive compared with ISH (P < 0.01). Seventy-four of 76 samples (97%) were positive according to HC2. Forty-six of 76 samples (61%) were positive according to ISH, including 80% and 70% of samples that were classified cytologically as moderate dysplasia and severe dysplasia, respectively. All women with underlying cervical intraepithelial neoplasia (CIN) lesions and 67% of women without CIN had positive HC2 samples. ISH scored 33%, 66%, 88%, and 73% of samples positive of women with no CIN, Grade 1 CIN (CIN 1), CIN 2, and CIN 3, respectively. The HC2 viral load was significantly higher in women who had a cytologic diagnosis of dysplasia (P < 0.01) and in women who had an underlying diagnosis of CIN (P < 0.01) compared with women who had neither. In addition, the viral load was significantly higher in ISH positive samples compared with ISH negative samples (P < 0.01). CONCLUSIONS: An increased HC2 viral load was associated with an increased chance of underlying high-grade CIN disease in women who tested hrHPV GP5+/6+-PCR positive. Moreover, although positive ISH results were associated with an increased overall viral load in the sample, the analytic sensitivity of ISH was too low to detect all women with prevalent high-grade CIN. 相似文献