液基细胞学与HPV检测对宫颈癌筛查的对比

 目的　评价液基细胞学 (ThinPrep)和肿瘤相关人乳头瘤病毒 (HPV)检测对宫颈癌的筛查能力。方法　随机选择 35～ 4 5岁妇女同时做ThinPrep ,自取材HPV检测 ,液基标本HPV检测和阴道镜活检。以阴道镜活检诊断为标准 ,比较 3种检查对宫颈鳞状上皮内高度病变 (HSIL ,CIN2 / 3)和鳞状细胞癌 (SCC)筛查的准确性。结果　 1997例受检者中阴道镜活检诊断HSIL(CIN2 / 3) 74例 ,SCC12例。ThinPrep与自取材和液基标本HPV检测的敏感性无显著差异 (P >0 .0 5 )而特异性显著高于后两者 (P <0 .0 1)。 3种检查有较好的一致性。结论　ThinPrep细胞学和HPV检测是筛查宫颈癌可选用的方法     

DH3与cobas4800在宫颈癌筛查中的效果对比研究

目的探讨DH3基于细胞学标本进行宫颈癌筛查的效果。方法选取2015年8月至2015年10月间山西阳城地区参加宫颈癌筛查(筛查方法为液基细胞学)的35～64岁妇女473例和2017年7月至2017年8月间同地区宫颈癌筛查(液基细胞学与cobas4800联合筛查)的37～66岁妇女740例,共1 213份标本。每份标本均行DH3和cobas4800检测,比较两种检测技术的一致性及临床效果。结果 DH3和cobas4800的14种高危型HPV、HPV16/18及其他高危型别阳性率分别为16. 9%和22. 1%、7. 3%和5. 5%及11. 1%和19. 0%,差异均有统计学意义(均P <0. 05),一致率依次为87. 2%、91. 7%和84. 9%。以CIN2+为临床终点,DH3和cobas4800的敏感度和特异度分别为100. 0%和84. 6%、100. 0%和81. 4%。结论 DH3基于细胞学标本进行宫颈癌筛查有良好的可行性。     

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。      

江西省修水县宫颈癌筛查分析

目的:了解我国宫颈癌高发之一的江西省修水妇女宫颈癌的流行状况和高危型人乳头状瘤病毒(HPV)感染与宫颈癌的关系。方法:对江西修水县2460名妇女进行妇科检查,宫颈刮片细胞学检查,对可疑病例采集其宫颈细胞进行高危型HPVDNA检测(HCⅡ)或对其行阴道镜检查。结果:以病理诊断为金标准,普查的2460例已婚妇女中宫颈癌10例,CINⅡ6例,CINⅠ8例。该人群宫颈癌的患病率为40650/10万,高危型HPVDNA检出率为245%(70/286),HPVDNA检出率随病变程度加重呈趋势性增高,χ2=773,P<001。结论:江西省修水县是宫颈癌高发区,女性生殖道高危型HPV感染是当地宫颈癌及宫颈内瘤样病变(CIN)高发的重要危险因素。对宫颈癌高发区进行有效筛查十分必要。     

温岭市已婚妇女宫颈癌组织筛查分析

[目的]了解温岭市已婚妇女宫颈癌筛查情况,探讨其筛查价值。[方法]2010年4～10月参加宫颈病变筛查妇女21566例,以液基细胞学(TCT)、人乳头瘤病毒(HPV)和阴道镜为筛查方法,活检组织病理学为诊断金标准。[结果]21566例患者中检出细胞学阳性共1024例,988例行HPV-DNA检测HPV感染405例,病理诊断宫颈上皮内瘤样变(CIN)Ⅰ139例,CINⅡ～Ⅲ83例,鳞状细胞癌(SCC)1例。农村居民宫颈病变患病率明显高于城镇居民(χ2=16.65,P<0.05)。[结论]通过有组织地对已婚妇女行宫颈癌筛查,可早期发现宫颈病变。     

阴道镜结果正常或低度病变妇女发生宫颈癌前病变的前瞻性风险分层研究

  目的  探讨细胞学、高危型人乳头瘤病毒（high risk human papillomavirus,hrHPV）分型对于阴道镜结果正常或低级别鳞状上皮内病变（low-grade squamous intraepithelial lesion,LSIL）妇女的风险预测作用。  方法  基于1999年6月在山西省建立的宫颈癌筛查队列,以2005年随访时阴道镜结果为正常或低度病变的596例妇女为研究对象,于2010年和2014年进行随访。分析hrHPV阴性组、hrHPV阳性组、HPV16/18阳性组、细胞学LSIL以下组和细胞学LSIL及以上组发生宫颈上皮内瘤样病变2级及以上（cervical intraepithelial neoplasia grade 2 or worse,CIN2+）的瞬时、5年和9年累积风险和相对危险度。  结果  细胞学LSIL以下组发生CIN2+的瞬时、5年和9年累积风险分别为0.2%、2.8%和4.2%,细胞学LSIL及以上组相应的风险分别为14.7%（RR=73.8,95% CI为9.7~561.5）、40.0%（RR=16.0,95% CI为8.2~31.1）和51.4%（RR=15.0,95% CI为8.3~27.0）。hrHPV阴性组发生CIN2+的瞬时风险、5年和9年累积风险较低,分别为0.6%、2.7%和3.8%,hrHPV阳性和HPV16/18阳性组发生CIN2+的风险逐渐升高,其中HPV16/18阳性组的相应风险分别为13.2%（RR=23.4,95% CI为5.1~106.9）、36.9%（RR=15.4,95% CI为6.9~34.3）和42.6%（RR=14.1,95% CI为6.8~29.2）。  结论  阴道镜结果正常或LSIL妇女,若细胞学结果为LSIL及以上或HPV16/18阳性,未来进展为高度宫颈癌前病变的风险较高,细胞学和HPV16/18分型可用于该人群的临床分流管理。      

宫颈液基细胞学与HPV-DNA检测技术联合应用在妇女病普查中的效果分析

目的:评价宫颈液基细胞学技术(TCT)与HC2-HPV-DNA检测技术联合应用在妇女病普查中的价值,探讨对细胞学异常,HPV阳性妇女进行筛查和随访的方法.方法:对2008年1月～2009年12月在本院进行妇女病普查的4 552例妇女进行宫颈TCT检查和HPV检查,诊断应用TBS分级标准,并对细胞学检查诊断为ASCUS以上者和HPV阳性者行阴道镜检查及活检.结果:4 552例妇女中,细胞学诊断为ASCUS以上者共343例(7.53%),HPV阳性659例(14.47%).对ASCUS以上的343例患者和HPV阳性659例均采用阴道镜检查及活检进行随访,检出宫颈鳞癌6例(0.13%),宫颈腺癌2例(0.04%),宫颈原位癌8例(0.18%),宫颈CIN 454例(9.97%),炎症232例(5.09%).结论:TCT检测结合高危型HPV检测技术的应用及TBS诊断标准能提高宫颈病变检出率.对细胞学筛查异常和HPV阳性的妇女可采用阴道镜及病理检查进行随访.     

cobas 4800与careHPV用于人乳头瘤病毒检测的对比研究

[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。     

318例高级别宫颈上皮内瘤变及宫颈癌患者的TCT和hrHPV检测分析

  目的  探讨如何使用现有的筛查方法, 减少高级别宫颈上皮内瘤变(cervical intraepithelial neoplasia grade 2 or 3, CIN2/3)及宫颈癌的漏诊。  方法  回顾性分析2014年6月至2018年8月318例中国医科大学附属航空总医院治疗的CIN2/3及宫颈癌患者的临床资料, 其中CIN2/3为296例、宫颈癌为22例, 采用宫颈液基薄层细胞学检查(thinprep cytology test, TCT)及高危型人乳头瘤病毒(high risk human papilloma virus, hrHPV)检测方法, 分析患者的年龄、TCT和hrHPV。  结果  296例CIN2/3患者中30~39岁患者为130例(43.92%)、占第1位, 20~29岁年轻患者为69例(23.31%)、占第3位。318例患者中TCT阳性为199例(62.58%), hrHPV阳性为308例(96.86%), 两者联合筛查阳性为313例, 阳性率为98.43%(313/318)。hrHPV分型检测主要亚型依次为16、52、58、33、18、31型。  结论  CIN2/3及宫颈癌的发病年龄年轻化, 年轻患者筛查不容忽视。TCT单独筛查较hrHPV单独筛查易漏诊高级别病变, TCT联合hrHPV筛查可提高检出率。TCT阴性, hrHPV非16、18亚型的其他hrHPV阳性, 尤其是hrHPV52、58、33、31亚型阳性患者也建议行阴道镜检查。      

实时光电学设备TruScreen~筛查宫颈癌的临床价值

目的评价实时光电学设备TruScreen检测技术在人群宫颈癌筛查中的价值。方法研究对象为2007年3月至2007年12月参加北京大学深圳医院针对深圳市贫困女性进行的宫颈癌筛查的妇女391名,年龄20～67岁。对所有接受筛查的妇女采用实时光电学设备TruScreen进行宫颈癌筛查,并采集宫颈脱落细胞,以液基细胞学技术行宫颈细胞学检查,以第二代杂交捕获(HC-Ⅱ)技术进行高危型HPV-DNA(HR-HPV)检测。筛查同时行阴道镜检查,对阴道镜疑诊低度鳞状上皮内病变(LSIL)及以上病变者,在可疑病变处取活检。为客观评价各种筛查方法,对各检测结果均采取盲法保存,于各检测结果确定后解盲。凡HC-Ⅱ检测HR-HPV阳性伴液基细胞学≥ASCUS,和(或)液基细胞学≥LSIL及TruScreen检查结果阳性,而筛查当时未取活检(阴道镜诊断非LSIL及以上病变)者,均于3个月内再次阴道镜下活检,明确诊断。病理为CINⅡ及以上病变者行宫颈电热圈坏切术(LEEP)手术,并取活检。有多次病理检查者以其中最高级别病理结果为该患者的最终诊断,病理诊断作为本研究4种筛查方法的评价标准。结果病理诊断CIN I 110例、CINⅡ5例、CINⅢ7例、宫颈浸润癌5例;慢性宫颈炎和鳞状上皮化生59例。TruScreen检测阳性率为28.2%;液基细胞学检测无明确诊断意义的鳞状上皮细胞病变(ASCUS)以上为23.3%,LSIL以上为7.2%;HR-HPV阳性率为34.3%。TruScreen、液基细胞学及HC-Ⅱ法HPV检查,各筛查方法对检出≥CINⅡ病变的敏感性、特异性、准确性、阳性预测值和阴性预测值分别为76.5%、77.3%、77.2%、13.3%和98.6%;液基细胞学以≥ASCUS为阳性各筛查评价指标分别为88.2%、79.7%、80.1%、16.5%和99.3%;以LSIL为阳性界值各指标为70.6%、95.7%、94.6%、42.9%和98.6%;HC-Ⅱ法HPV为94.1%、68.5%、69.6、11.9%和99.6%。结论实时光电学设备TruScreen进行宫颈癌初筛,筛查效率指标中虽敏感性不及HC-Ⅱ法HPV检测高,但与宫颈细胞学检查相当。作为一种新的宫颈癌筛查技术,具有检测无创无痛、用时较短、实时报告结果等优点,适用于贫困地区大样本人群筛查。     

Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: the FASE study

The APTIMA HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture 2; HC2) and liquid-based cytology (LBC; using PreservCyt ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N = 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US+ in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN2+ (92.0% and 96.7%) and CIN3+ (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN2+ and 73.3% for CIN3+). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.     

两种高危型HPV检测方法在宫颈癌早期筛查中的应用

  目的  比较两种高危型HPV检测方法在健康体检妇女宫颈癌早期筛查中的应用,选择更适用于宫颈癌早期筛查的检测方法,保护易感人群。  方法  应用荧光定量PCR方法和HC2-HPV-DNA两种方法检测健康体检妇女中13种高危型HPV病毒感染情况,并按照年龄分为23~29岁、30~39岁、40~49岁和50~58岁4个年龄组,应用统计学方法对两种检测方法的结果进行分析。  结果  在879例健康体检妇女中,荧光定量PCR和HC2-HPV-DNA两种方法检出13种高危型HPV阳性率分别为15.93%（140/879）和11.83%（104/879）,两种方法同时检出阳性率为9.56%（84/879）,两种方法同时检出阴性率为81.80%（719/879）。两种方法结果均示在40~49岁和50~58岁两个年龄组中,高危型HPV感染率明显升高。统计学分析显示荧光定量PCR和HC2-HPV-DNA两种方法差异有统计学意义（P < 0.05）。  结论  HC2-HPV-DNA在13种高危型HPV检测中优于荧光定量PCR方法,更适合大规模健康体检中的应用,可用于大规模人群宫颈癌早期筛查,尤其对于40岁以上妇女进行高危型HPV检测,可有效预防宫颈癌发生。      

A comparison of single and combined visual, cytologic, and virologic tests as screening strategies in a region at high risk of cervical cancer.

Increased understanding of human papillomavirus (HPV) infection as the central cause of cervical cancer has permitted the development of improved screening techniques. To evaluate their usefulness, we evaluated the performance of multiple screening methods concurrently in a large population-based cohort of >8500 nonvirginal women without hysterectomies, whom we followed prospectively in a high-risk region of Latin America. Using Youden's index as a measure of the trade-off between sensitivity and specificity, we estimated the performances of a visual screening method (cervicography), conventional cytology, liquid-based cytology (ThinPrep), and DNA testing for 13 oncogenic HPV types. The reference standard of disease was neoplasia > or = cervical intraepithelial neoplasia grade 3 (CIN 3), defined as histologically confirmed CIN 3 detected within 2 years of enrollment (n=90) or invasive cancer detected within 7 years (n=20). We analyzed each technique alone and in paired combinations (n=112 possible strategies), and evaluated the significance of differences between strategies using a paired Z test that equally weighted sensitivity and specificity. As a single test, either liquid-based cytology or HPV DNA testing was significantly more accurate than conventional cytology or cervicography. Paired tests incorporating either liquid-based cytology or HPV DNA testing were not substantially more accurate than either of those two test strategies alone. However, a possibly useful synergy was observed between the conventional smear and cervicography. Consideration of age or behavioral risk profiles did not alter any of these conclusions. Overall, we conclude that highly accurate screening for cervical cancer and CIN 3 is now technically feasible. The remaining vital issue is to extend improved cervical cancer prevention programs to resource-poor regions.     

A Descriptive Study of Different Methods of Cervical Cancer Screening among Ever-Married Women in 35-Year and 45-Year Cohorts in Kalutara District,Sri Lanka

Objective: Screening for cervical cancer in Sri Lankan females with Pap smears (conventional cytology) has shown no marked reduction in cervical cancer incidence over the past two decades. The study aims to compare the efficacy of Pap smear, with other screening tools such as Liquid Based Cytology (LBC) and Human Papilloma Virus/deoxyribonucleic acid (HPV/DNA) (using cobas 4800) in detection of underlying cervical intraepithelial neoplasia (CIN) and cervical cancer among 35 and 45 year old ever married women in Kalutara districtin Sri Lanka. Methods: Women from 35-year cohort and 45-year cohort were selected from all Public Health Midwife areas (n=413) in Kalutara district by random sampling. Pap smear, LBC, and HPV/DNA specimen were collected s from women who attended the Well Woman Clinics (WWC) . Women with positive results from any method were confirmed by colposcopy.  Results: Of the, 510 and 502 women in the 35-year cohort and 45-year cohort, respectively, included in the analysis, nine women among 35-year cohort (1.8%) and 7 women among 45-year cohort (1.4%) had cytological abnormality (positive results) with Pap smears. Thirteen women among 35-year cohort (2.5%) and 10 women among 45-year cohort (2%) age groups had cytological abnormality (positive results) with Liquid Based Cytology reports. Total of 32 women among 35-year cohort (6.2%) and 24 women among 45-year cohort (4.8%)  were positive for HPV/DNA test. Of  the women tested positive on screening, colposcopy revealed that HPV/DNA method was superior to Pap and LBC for detecting CIN while the results of latter two were comparable. Conclusions and Recommendations: The CIN detection rate by colposcopy was high with HPV/DNA screening with cobas 4800, whereas the detection rate by LBC was insignificantly higher than Pap smears.     

Significance of human telomerase RNA gene amplification detection for cervical cancer screening

Aim: Liquid-based cytology is the most often used method for cervical cancer screening, but it is relativelyinsensitive and frequently gives equivocal results. Used as a complementary procedure, the high-risk humanpapillomavirus (HPV) DNA test is highly sensitive but not very specific. The human telomerase RNA gene (TERC)is the most often amplified oncogene that is observed in cervical precancerous lesions. We assessed genomicamplification of TERC in liquid-based cytological specimens to explore the optimal strategy of using this forcervical cancer screening. Methods: Six hundred and seventy-one residual cytological specimens were obtainedfrom outpatients aged 25 to 64 years. The specimens were evaluated by the Digene Hybrid Capture 2 (HC2) HPVDNA test and fluorescence in situ hybridization (FISH) with a chromosome probe to TERC (3q26). Colposcopicexamination and histological evaluation were performed where indicated. Results: The TERC positive rate washigher in the CIN2+ (CIN2, CIN3 and SCC) group than in the normal and CIN 1 groups (90.0% vs. 10.4%, p <0.01). In comparison with the HC2 HPV DNA test, the TERC amplification test had lower sensitivity but higherspecificity (90.0% vs. 100.0%, 89.6% vs. 44.0%, respectively). TERC amplification test used in conjunctionwith the HC2 HPV DNA test showed a combination of 90.0% sensitivity and 92.2% specificity. Conclusion: TheTERC amplification test can be used to diagnose cervical precancerous lesions. TERC and HPV DNA co-testingshows an optimal combination of sensitivity and specificity for cervical cancer screening.     

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。     

新疆维吾尔族女性人乳头瘤病毒感染与宫颈癌相关性的流行病学调查

目的　了解新疆维吾尔族女性人乳头瘤病毒（ＨＰＶ）感染及宫颈癌的发病状况,为新疆宫颈癌预防和筛查提供数据。方法　于２００６年采用整群抽样方法选择新疆于田县有性生活、１６～５９岁维吾尔族女性,按年龄分层入组,依次行宫颈液基细胞学检查和ＨＰＶ检测。意义不明的不典型鳞状细胞（ＡＳＣＵＳ）以上或ＨＰＶ阳性者行阴道镜检查及必要的宫颈活检。结果　新疆维吾尔族妇女高危型、低危型和总体ＨＰＶ感染率分别为７.２５％、１.５９％和８.２７％。ＣＩＮⅡ级以上病变和宫颈癌现患率分别为１.９３％和０.２３％。高危型ＨＰＶ在细胞学ＡＳＣＵＳ、鳞状上皮内低度病变（ＬＳＩＬ）和鳞状上皮内高度病变（ＨＳＩＬ）中的比例分别为１３.４６％、６４.７１％和９０.００％;高危型ＨＰＶ在ＣＩＮⅠ、ＣＩＮⅡ、ＣＩＮⅢ和ＩＣＣ的比例分别为６６.６７％、８３.３３％、１００.００％和１００.００％。ＨＰＶ感染率随宫颈病变级别增加有增高趋势,但在ＣＩＮⅡ级以上病变中无统计学差异。结论　新疆维吾尔族女性ＨＰＶ感染率低于我国汉族女性,但宫颈癌现患率高于我国城市汉族女性,低于一些农村汉族女性。新疆维吾尔族女性ＨＰＶ感染率在不同级别宫颈上皮内瘤变中的分布趋势与中国其他地区相似,但同时具有自身民族特征。     

Risk of CIN2 or more severe lesions after negative HPV-mRNA E6/E7 overexpression assay and after negative HPV-DNA test: Concurrent cohorts with a 5-year follow-up

Aim of this study was to compare the 5-year risk of cervical intraepithelial neoplasia grade 2+ (CIN2+)/CIN3+ and the performance parameters at 3-year rescreening of a negative E6/E7 mRNA-human papillomavirus (HPV) test with those of a HPV-DNA-negative test. We studied a cohort of HPV-negative women tested with the Aptima HPV-mRNA Assay (“HPV-mRNA cohort”) versus a cohort of HPV negatives tested with the Hybrid Capture 2 (HC2) DNA test living in neighboring areas. Both cohorts were rescreened after 3 years by a HPV-DNA test (HC2 or Cobas 4800 HPV test). HPV test positivity, referral to colposcopy and detection of CIN2+ at 3-year rescreening were computed. The Veneto Cancer Registry was checked to search for invasive cancers and CIN3 diagnosed up to 5 years from the negative baseline test. Some 22,338 HPV-mRNA and 68,695 HPV-DNA-negative women were invited to 3-year rescreening, and, respectively, 16,641 (74.5%) and 54,630 (79.6%) complied with the invitation. The proportion of HPV-positive tests, referral to colposcopy and detection of CIN2+ in the HPV-mRNA and HPV-DNA cohorts were, respectively. 4.0 and 3.9% (ratio 1.08; 95% confidence interval [CI] 0.99–1.17), 2.6 and 2.5% (ratio 1.06, 95% CI 0.95–1.18) and 1.4 and 1.7‰ (ratio 0.85, 95% CI 0.54–1.33). The relative 5-year cumulative risk of cancer and of CIN2+ in the HPV-mRNA and HPV-DNA cohorts were 4.5 and 8.7/100,000 (ratio 0.51; 95%CI 0.01–4.22) and 1.1 and 1.5/1,000 (ratio 0.74; 95%CI 0.45–1.16), respectively. A negative HPV-mRNA test confers a risk of invasive cervical carcinoma and of CIN2+ at 5 years comparable to that of a negative HPV-DNA test.