高危型人乳头瘤病毒(Human papillomavirus,HPV)持续感染可导致癌前病变,以HPV-16/HPV-18型感染最为常见,但HPV感染所产生的中和抗体(Neutralizing Antibody,nAb)对宫颈癌及癌前病变的相关关系尚不明确.本研究旨在探索HPV-16/HPV-18在不同的中和抗体与DNA感染状态下的年龄分布及其和宫颈组织学病变的相关性.通过横断面研究,本研究于2012年11月至2013年4月招募7372名18～45岁健康女性.收集每个受试者血清用假病毒中和抗体定性检测HPV-16和HPV-18中和抗体;采集宫颈细胞学样本用于液基细胞学诊断,并用HPV SPF10 PCR-DEIA-LiPA25分型检测系统及HPV-16/HPV-18型特异性DNA酶联免疫测定法联合检测HPV-16/HPV-18 DNA;召回细胞学异常的受试者在阴道镜下采集组织学标本进行病理诊断.结果 显示,HPV-16和HPV-18中和抗体(nAb)阳性率为12.56％,4.94％,DNA阳性率为2.69％和0.92％,nAb与DNA的一致率较低.HPV-16和HPV-18DNA-/nAb+人群在27～45岁的大龄组女性中比例均高于18～26岁女性.DNA+/nAb+和DNA+/nAb-人群在18～26岁和27～45岁年龄组中比例无统计学差异.多因素分析结果显示,与DNA-/nAb-人群相比,HPV-16 DNA +/nAb-人群发生宫颈高度病变CIN2+的风险较高,而DNA+/nAb+则风险更高,调整OR分别为33.80 (95％CI:16.50～69.23)和63.86 (95％CI:36.57～111.52);HPV-18呈现相同的规律,调整OR分别为5.39 (95％CI:1.14～25.56)和7.83 (1.61～38.14).HPV-16或HPV-18 DNA阳性的女性是宫颈组织学病变的高危人群,而若DNA阳性伴有同型抗体阳性的人群则风险更高,这对于探究宫颈病变的自然发病机理具有一定意义.

Objectives: Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naive (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naive women in different age groups is important for developing HPV vaccination strategies. Methods: From November 2012 to April 2013, a total of 7372 healthy women aged 18-45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay. Results: The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0-15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18-26 years) and middle-aged women (27-45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naive to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naive to at least one HPV type (HPV-16 or HPV-18). Discussion: This study revealed that the majority of Chinese women aged 18-26 years and 27-45 years were naive to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination. (C) 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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.

Objective: To evaluate the clinical performance of HPV genotyping with cytology for detecting cervical precancer among women attending co-testing. Methods: A total of 2 883 females who participated in cervical cancer screening program were recruited from Erdos in 2016. All the participants were tested by cytology and HPV genotyping. In 2017, women with abnormal cytology results or HPV positive were followed up. Pathological cervical intraepithelial neoplasia (CIN) 2+ was the study end-point. Clinical performance indexes were calculated, including sensitivity, specificity, positive predictive value, negative predictive value, referral rate and missed cases. Results: INNO-LiPA resulted in a detection rate of 18.87%(544/2 883) for the 14-type high risk HPV. HPV16 was the most common infectious genotype (4.06%), followed by HPV52 (3.61%), HPV51 (2.50%), HPV58 (1.98%), and HPV18 (1.56%). With more HPV genotypes added into the group, sensitivity increased and the specificity decreased. Addition of HPV16, 58, 33, 39, 52, 18, 31 for detection lead to the maximun value of area under the curve (AUC)=0.913 (95%CI: 0.882-0.944). Compared with traditional screening method by cytology, cotesting decreased the number of missed diagnosis. Meanwhile, the fifth method (co-testing: triage of women with HPV16/18+ , cytological minor abnormalities and HPV58, 33, 39, 52, 31+ or cytological high grade abnormalities) did not increase referral rate (8.99% vs. 8.71%, P=0.525), with five cases of missed diagnosis (sensitivity of 92.1% and specificity of 93.2%). Conclusions: Co-testing with triage of women with HPV16/18+ , cytological minor abnormalities and HPV58, 33, 39, 52, 31+ or cytological high grade abnormalities would provide better clinical performance. In co-testing, triage of HPV16/18 was used in women with normal cytology; triage of HPV58, 33, 39, 52 and 31 was used in women with low-grade abnormal cytology; referral colposcopy was used in women with high-grade abnormal cytology, which would provide better clinical performance.

Objective: To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+). Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups. Results: Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ(2)=19.00, P<0.001), and the specificity were 86.2% and 78.8% (χ(2)=2 067.00, P<0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z=6.16, P<0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ(2)=132.00, P<0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting. Conclusion: Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

Objective: To analyze the type-specific prevalence of human papillomavirus (HPV) among women aged 18-45 years from the general population in Liuzhou, Guangxi Zhuang Autonomous Region. Methods: Totally, 2 300 women aged 18-45 years old were enrolled in Liuzhou,from March to July, 2013. Cervical exfoliated cells were collected for liquid based cytological and HPV DNA tests. Women were referred to colposcopy exam, based on the clinical practice guideline. Results: Overall, the prevalence rates of any HPV or oncogenic HPV appeared as 22.7% (95% CI: 21.0%-24.4%) and 17.3% (95% CI: 16.0%-19.1%), respectively in this population under study. The high-risk HPV prevalence peaked at the age groups of 18-25 and 41-45, increasing along with the severity through cytological and histological tests. Statistically significant differences between the prevalence of CIN2+ (Cervical intraepithelial neoplasia 2+) in women older than 26 years (1.7%, 95% CI: 1.0%-2.4%) and 18-25 years (1.2%, 95% CI: 0.5%-1.9%) of age, were not observed. Among samples diagnosed as CIN2+, positivity of HPV bivalent (16/18) and nine-valent (6/11/16/18/31/33/45/52/58) vaccine, related high risks on the types of HPV types appeared as 44.1% and 97.1%. Conclusions: The age-specific HPV prevalence rates in the general women aged 18-45 in Liuzhou presented as having bimodal distribution, suggesting that the disease burden of cervical diseases in women aged 26-45 years should not be ignored. Nine-valent HPV vaccine might provide more effective prevention outcomes on cervical cancer in China.

[Objective] To evaluate the role of HPV16/18 DNA genotyping in predicting the risk of cervical precancerous or cancerous lesions in women with atypical squamous cells of undetermined significance(ASC -US),compared with hrHPV DNA testing.[Methods] The current study was conducted based on the cohort of Shanxi Province Cervical Cancer Screening Study Ⅰ (SPOCCS I).During the follow-up,women received hrHPV DNA testing (hybird capture 2,HC2),liquid-based cytology and visual inspection with acetic acid concurrently.Those with any positive screening result would be transferred to colposcopy and take biopsies if necessary.Meanwhile,HPV genotyping was performed on residual cervical exfoliated cell samples in HC2-positive women using reverse linear probe hybridization assay (LiPA).416 ASC-US women from the cohort were included to estimate the immediate risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by hrHPV DNA,HPV16/18 genotyping status,as well as their clinical performances.The 5-year cumulative risk of CIN2+ and relative risk were assessed in the 253 ASC-US women detected in 2005.[Results] Among women with positive hrHPV,those infected with HPV16/18 had higher immediate risk of CIN2+ (9.7％) than those with other hrHPV infections (3.8％),but there was no significantly statistical difference (0R=2.7,95％CI:0.4～17.3).No case was found in hrHPV-negative women.Compared with hrHPV-negative women (1.9％),the 5-year cumulative risks of CIN2+ increased in groups of other hrHPV type positive [5.3％,RR=2.7(95％CI:0.3～23.0)],hrHPV positive [8.5％,RR=4.5(95％CI:1.1 ～17.8)] and HPV16/18positive (11.8％,RR=6.2 (95％CI:1.1～33.9)].Compared with hrHPV DNA testing,the sensitivity of HPV 16/18 genotyping for detecting CIN2+ declined [relative sensitivity:0.6 (95％CI:0.3～1.2)],and the specificity to exclude CIN2+ increased [relative specificity:1.3(1.2～1.4)].[Conclusion] Triaging ASC-US women with HPV16/18 genotyping can obtain higher specificity while losing some sensitivity.HPV16/18 genotyping can discriminate the instant and long-term CIN2+ risk in hrHPV-positive population,so it can be used to manage or triage ASC-US women.

Objective To assess the triage strategy suitable for HPV positive women in cervical cancer screening in rural China,and provid scientific evidence for cervical cancer screening in the real world.Methods Women aged 35-64 years were recruited from Xiangyuan County and Yangcheng County in Shanxi Province between July 2015 and October 2015 for cervical cancer screening.Care HPV detection method was used as the primary screening technique,and after the initial screening,women with positive HPV results were randomly divided into three groups:cytology triage (82 patients),VIA/VILI triage (83 patients) and direct colposcopy without triage (83 patients).Cytology and VIA/VILI positive women transferred to colposcopy.If colposcopy screening showed abnormal results,biopsy was performed for pathological doagnosis.Results A total of 1503 women were enrolled.The positive rate of HPV was 16.5％ (248/1503).The detection rates of moderate and above cervical intraepithelial neoplasia (CIN2 +) was 0.7％ (11/1503).Among the 248 women,237 women completed triage,and the compliance rate was 95.6％ (237/248).There were 81,79 and 77 women in cytology triage group,VIA/VILI triage group and non shunt direct colposcopy group respectively.The triage positive rate,CIN2 + detection rate and positive predictive value were 19.8％,1.2％ and 11.1％ respectively for cytology group,17.5％,3.6％ and 21.4％ respectively for VIA/VILI group,and 19.5％,8.4％ and 9.5％ for colposcopy group.There were no obvious statistical difference in all the above positive rates and CIN2 + detection rates (all P ＞ 0.05).There was an increasing trend of HPV positive rates with the increasing of age(P ＜ 0.05),but colposcopy group showed a down trend (P ＜ 0.05).No obvious differences were found in changes of positive rates with the increasing of age between VIA/VILI group and cytology group (P ＞ 0.05).Conclusion Among the three methods,VIA/VILI may be a suitable triaged method for HPV positive women in rural China.

Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) combined with bronchial brushing cytology for detecting lung cancer. Methods: Centromeric enumeration probes (CEPs) for chromosomes 7, 8 and 17 were used in FISH assay. The combination of FISH and cytology was analyzed in 69 bronchial brushing specimens. Results: The positive rates of CEP7, CEP8 and CEP17 in malignant cases diagnosed by cytology were 50.0%, 80.8% and 65.4%, respectively. CEP8 probe showed significantly higher positive rate than CEP7 (P=0.015). In the samples of suspicious of malignancy, the positive rates of CEP7, CEP8 and CEP17 were 46.6%, 66.7% and 58.8%, respectively. While in atypical cases, the positive rates of these three probes were 20.0%, 33.3% and 25.0%, respectively. There was no statistical difference between suspicious of malignancy and atypical cases (P>0.05) as well as between malignant and suspicious of malignancy (P>0.05). No chromosome aberrations were found in normal cases diagnosed by cytology. The positive rates of these three probes in adenocarcinoma (ADC) were slightly higher than those in squamous cell carcinoma and small cell lung cancer. However, only CEP8 probe showed statistically difference between ADC and small cell lung cancer (P=0.044). The combination of cytology and FISH using any one of the three-probe set (CEP7, CEP8 and CEP17) showed the sensitivity and specificity of 80.3% and 100.0%, while those of cytology were 54.1% and 100.0%, respectively. Conclusions: FISH combined with cytomorphology assisted the cytology diagnosis of suspicious of malignancy and atypical cases. Therefore, it significantly improved the diagnostic sensitivity for lung cancer without sacrificing specificity.

We wished to analyze the prevalence of human papillomavirus (HPV) 16/18 neutralizing antibody,DNA and precancerous Lesions of Cervical Cancer(PLCC) among women aged 18～45 years from the general population in Liuzhou,Guangxi Province,China.From March to July,2013,totally 2,300 women aged 18～45years were enrolled in Liuzhou.Neutralization of HPV16/18 was detected by the pseudovirionbased neutralization assay and Cervical exfoliated cells were collected for liquid-based cytological and HPV DNA tests.Women were referred to colposcopy based on clinical practice guidelines.The x2 test for trend was used to analyze the prevalence of HPV DNA and the positive rate of HPV neutralizing antibody in different age groups.The influencing factors of PLCC was analyzed by logistic regression.Amongwomen aged 18～45 years from the general population in Liuzhou,HPV16 DNA and/or neutralizing antibodies were positive in 364 (15.8％;95％confidence interval(CI):14.4,17.4),andHPV18 DNA and/or neutralizing antibodies were positive in 164 (7.1％;6.1,8.3).The x2 test for cervical intraepithelial neoplasia (CIN)3 was statistically significant in different age groups (P=0.005).Among samples diagnosed as CIN1+ and CIN2+,HPV16 and HPV18 DNA positive was the main risk factor.Neutralizing antibodies produced after natural HPV infection make no statistically significant effect on Precancerous Lesions of Cervical Cancer.HPV16/18 infection was a risk factor for PLCC.Neutralizing antibodies produced after natural HPV infection had no statistically significant effect onPLCC.HPV16/18 DNA infection was a risk factor for PLCC.These data suggest that a HPV16/18 vaccine would be the primary choice to prevent HPV infection and the precancerous lesions in women aged 18～45 years.

Objective To evaluate the 15 years changing trends of prevalence of high risk HPV (HR?HPV) infection and the risks of cervical cancer and precancerous lesions (CIN2+) among a Chinese rural population. Methods The screening cohort with 1 997 women aged 35 to 45 years old was built in 1999 in Xiangyuan County, Shanxi province ( SPOCCS?I) and followed up by cytology and HR?HPV testing in the years of 2005, 2010, and 2014. The changes of HR?HPV prevalence and the risks of cervical precancerous lesions with CIN2+ as the endpoints were analyzed during the past 15 years. Results The detection rates of HPV infection and CIN2+ were 15.7%?22.3% and 1.1%?4.3% for the baseline visit and the other 3 follow?ups, respectively. The cumulative risk of CIN2+ in HR?HPV positive women at baseline was significantly higher than HR?HPV negative women ( P<0.01) during the 15?year follow?up. The risk of CIN2+ in the four?times HPV positive group was 40. 0%, while the group with four?times negative HPV results was 0.6% (Adjusted RR = 55.0, 95% CI: 11.3 to 268.4). Conclusions The prevalence of HR?HPV infection and CIN2+ lesions were high in Xiangyuan county during the 15 years. HR?HPV positivity elevated the risk of CIN2+ compared to women whose HR?HPV test was negative. The risks of CIN2+incidence in 6 years were low among women with negative HR?HPV test. The risk of CIN2+ increased with the numbers of HPV infection events. The screening interval could be extended to 5?6 years.

目的 探讨细胞病理学宫颈非典型腺细胞(AGC)诊断的临床意义.方法 对细胞学诊断141例AGC进行随访,与有组织病理学诊断的117例进行对照总结.结果 宫颈细胞学诊断26345例中,细胞学异常诊断2966例(1 1.3％),其中腺细胞异常诊断335例(1.27％),AGC诊断141例(0.54％).141例AGC中117例有随访病理结果,10例病理诊断良性,8例为鳞状上皮病变,97例腺上皮病变(3例宫内膜非典型增生、94例为宫内膜/卵巢/宫颈腺癌),2例宫内膜肉瘤.9例癌前病变＜50岁者6例(66.7％),98例恶性肿瘤≥50岁者70例(71.4％),两组差异显著(P＜0.05).85例腺癌患者中,早期宫内膜癌占82.9％(58/70),晚期卵巢腺癌占73.3％(11/15).结论 细胞学AGC诊断在随诊病理结果中多数为宫内膜腺癌或卵巢腺癌,少数为鳞状上皮内病变或鳞癌;＜50岁者更多见于上皮内病变,≥50岁者有更高的恶性肿瘤风险.

OBJECTIVE:To assess the risk of cervical cancer and high grade cervical intraepithelial in women with negative human papillomavirus (HPV) and cytology atypical squamous cells of undetermined significance (ASC-US) and to provide evidence for clinical management.METHODS:We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. Totally, 30 371 women aged 17-59 were included in these studies. All women received liquid-based cytology test (LBC), HPV testing (hybrid capture 2 test, HC2) and visual inspection with acetic acid test (VIA). Women with any positive result from above tests were referred to colposcopic examination. Totally, 28 810 women with complete results from HPV, cytology and pathology were included in the final analysis. Women with negative HPV (LBC-/HPV-) or negative cytology (LBC-) results served as the control, respectively. Risk on high grade cervical intraepithelial neoplasia (CIN2+) was calculated for women with HPV negative and ASC-US results (ASC-US/HPV-).RESULTS:There were 22 003 women with LBC-/HPV-, 24 139 women with LBC-, and 1 834 with ASC-US/HPV- indentified in our study. CIN2+prevalence rates to the above women appeared as 0.05%, 0.36% and 0.16%, respectively. Compared with women with LBC-/HPV- and women with LBC-, the odds ratios (ORs) for CIN2+in women with ASC-US/HPV-were 3.00 (95%CI: 0.85-10.65) and 0.46 (95%CI:0.15-1.45), with adjusted ORs as 4.00 (95%CI: 1.08-14.87) and 0.47(95%CI: 0.15-1.49), respectively.CONCLUSIONS:The risk of CIN2+ in women with ASC-US/HPV- was in between the risks of women with LBC-/HPV- or with LBC-. Based on the "equal risk, equal management" principle, women with ASC-US/HPV- were suggested to be followed under the '3-year interval' program, which was the same as for those cytology negative women. However, in areas with limited health resources, the follow-up interval can be extended to 5 years, similar to the management on women with LBC-/HPV-.

OBJECTIVE:To investigate the value of the liquid-based cytology (LBC) of brushing specimens obtained via fiberoptic bronchoscopy for clinical diagnosis of lung cancer. METHODS:We retrospectively analyzed the LBC cases in our hospital from January 2011 to May 2012, and evaluate its role in the diagnosis of lung cancer. RESULTS:The clinical data of a total of 4 380 cases were reviewed and 3 763 of them had histopathological or clinical follow-up results (including 3 306 lung cancer cases and 457 benign lesion cases). The sensitivity, specificity, and accuracy of LBC diagnosis for lung cancer were 72.4% (2 392/3 306), 99.3% (454/457) and 75.6% (2 846/3 763), respectively. Of the 1 992 lung cancer cases diagnosed by brushing LBC, 528 cases (26.5%) were failed to take forceps biopsy and 113 cases (5.7%) showed negative forceps biopsy results. The accurate rate of subtyping of LBC for non-small cell carcinoma and small cell carcinoma was 99.0% (1 487/1 502) (P < 0.001). Take the resection histopathology as gold standard, the accurate rates of subtyping squamous cell carcinoma, adenocarcinoma and small cell carcinoma by LBC were 95.6% (351/367), 95.6% (351/367) and 100% (367/367), respectively, (P < 0.001). The accurate rates of subtyping of squamous cell carcinoma, adenocarcinoma and small cell carcinoma by forceps biopsy were 97.0% (293/302), 97.4% (294/302) and 99.7% (301/302), respectively, (Kappa = 0.895, P < 0.001). There was no significant difference in subtyping respectively between forceps biopsy and brushing LBC (P > 0.05). CONCLUSIONS:Fiberoptic bronchoscopic brushing liquid-based cytology can significantly improve the detection rate of lung cancer, and have a high specificity and accurate rate of subtyping. It is an effective tool for the diagnosis and subtyping of lung cancer.

Objective: We aimed to clarify the influence of ThinPrep preparation, nodule size and guidance mode on the accuracy of thyroid fine-needle aspiration (FNA). Methods: A total of 1,240 thyroid FNAs were reviewed and 489 cases with histological correlations were enrolled in this study. Results: Of the 489 total cases examined, 101 were processed with both ThinPrep and conventional preparation and 388 entirely with ThinPrep. The overall nondiagnostic rate, sensitivity and accuracy of FNA were 2.0, 91.0 and 89.4%, respectively. The cases with a preoperative ultrasound (n = 469) were grouped according to nodule size. The nondiagnostic rate, sensitivity and accuracy of FNA did not differ significantly with nodule size (p1 = 0.339, p2 = 0.179, p3 = 0.119). A total of 101 resections were performed with palpation-guided FNA and 388 were performed with ultrasound-guided FNA. The nondiagnostic rates, sensitivity and accuracy of FNA were similar in these two groups. Conclusions: The ThinPrep technique is a valid method for thyroid FNA and is effective for thyroid nodules ≥0.5 cm. The reliability of FNA results is not reduced with larger nodules. The use of palpation-guided FNA for palpable solid nodules is also effective.

Objective To evaluate the clinical application value of intraoperative effusion or washing cytology and its accuracy. Method 521 patients in our hospital were enrolled. Their cytological diagnosis and histological diagnosis after surgery were compared to analyses the characteristics of the smears by reviewing the false-positive and false-negative slides and to evaluate its accuracy and clinical application value. Result During the 521 intraoperatively obtained samples the detection rate of the malignant cells was 40. 32%, whereas the detection rate of the cases that had peritoneal metastasis by histopathology was 84. 9%. In the current study, there were 9 false-positive and 18 false-negative cases. The main reason for the false-positive was that it's difficult to discriminate the endometriosis or the mesothelial cell hyperplasia from the well-differentiated adenocarcinoma, while the main reason for the false-neg-ative was the low detection sensitivity caused by the Inflammatory cells and the hemocytes. Conclusion The rate of detection of intraoperative cytology were relatively high and it had certain accuracy. Therefore it had reference value for the patients' follow-up treatments and prognosis.

目的 探讨卵巢交界性囊腺瘤术中腹水或冲洗液细胞学检出率与细胞学涂片的形态学特征.方法 收集521例术中积液或冲洗液细胞学涂片,回顾性分析了30例卵巢交界性囊腺瘤细胞学涂片,探讨其细胞形态特征及诊断价值.结果 521例积液或冲洗液中,30例为卵巢交界性囊腺瘤,细胞学检出16例(53.3％).30例中18例为浆液性,10例为黏液性,2例为混合性.卵巢交界性囊腺瘤细胞学涂片显示,细胞异型性不明显,有明显上皮结构可提示为肿瘤而非间皮细胞.增生间皮细胞偶可呈乳头结构,但乳头较平铺,无三维立体感.结论 卵巢浆液性交界性囊腺瘤的细胞学检出率相对较高.术中腹水或冲洗液细胞学涂片中,卵巢交界性囊腺瘤细胞/卵巢腺癌细胞与增生活跃的间皮细胞容易鉴别,而交界性囊腺瘤细胞与腺癌细胞较难鉴别.染色质明显增粗和核形不规则是鉴别两者最有意义的形态学特征.

Objective To validate the feasibility for detecting EGFR and k-ras mutations using cytological specimens.Methods Cytological specimens including fine-needle aspiration (FNA),pleural effusion (PLE) and fiberoptic bronchoscopic (FOB) brushing were collected from patients with non-small cell lung cancer (NSCLC) from January 2011 to July 2011 at the Department of Cytology,Cancer Hospital,Chinese Academy of Medical Sciences (CHCAMS).Polymerase chain reaction (PCR) was carried out to amplify EGFR exons 18-21 and k-ras codons 12-13,and then the PCR products sequencing and analysis were performed.Results Fifty cytological specimens were collected including 19 cases of FOB,9 cases of FNA,22 cases of PLE.Of them DNA was successfully extracted in 43 cases,and specific PCR amplification products sequencing were performed in 42 cases.EGFR mutations were detected in 14 of 42 specimens (33.3％),the frequencies of EGFR mutations in exons 19,20 and 21 were 16.7％ (7/42),4.8％ (2/42) and 11.9％ (5/42),respectively,and no mutation was found in exon 18.Higher frequencies of EGFR mutations were detected in exons 19 and 21 (85.7％).Mutations were identified in 38.7％ (12/31) cases of adenocarcinoma.K-ras mutations were found in 2 of 42 specimens (4.8％).EGFR and K-ras mutations were not found in the same case.Conclusions Cytological specimens are feasible for detecting EGFR and K-ras mutation.This is especially beneficial in patients in whom histological materials can not be obtained.

Objective:This study aimed to evaluate the feasibility and utility of cobas 4800 human papilloma virus (HPV) test as a primary screening test and a triage tool in cervical cancer screening. Methods:A total of 856 unscreened women subjects over 21 years of age and have engaged in sexual activities were recruited from Henan, China in 2011. All subjects were screened through cobas 4800 HPV, Hybrid Capture 2 (HC2) technology, ThinPrep liquid-based cytology, and colposcopy. Any visible lesion was directly biopsied through colposcopy. Random biopsies in four quadrants at the squamocolumnar junction and endocervical curettage were performed when apparent colposcopic abnormality was not observed, but at least one of the HPV tests was positive. Pathologic diagnosis was used as the golden standard to evaluate the performance of the screening tests. Results:Measured as a primary screening test, the sensitivity and specificity of the cobas 4 800 HPV test in detecting gradeⅡcervical intraepithelial neoplasia (CIN2) and CIN2+in patients reached 94.4%and 63.2%, respectively, compared with 94.4%and 63.9%of the HC2 test. The concordance rate in detecting HPV DNA between cobas 4800 HPV and HC2 tests was 83.4%(κ=0.65). The cobas 4800 HPV test could detect all CIN2+cases that were undetected by the ThinPrep liquid-based cytologic test. The positive predictive value of the HPV 16/18 typing test in detecting CIN2+lesions was twice as high as that of the HC2 test (2.13×). In the CIN2+cases, the women subjects infected with HPV16/18 were 5.4 years younger than those infected with other types of HPV. Conclusion:Satisfactory consistency and similar accuracy between the cobas 4800 HPV and HC2 tests were observed. However, cobas 4 800 HPV test is superior in detecting high-risk HPV types. This test could provide more sensitive and efficient strategies compared with the ThinPrep liquid-based cytology. Cobas 4 800 HPV can also identify the sub-genotypes of high-risk HPV16/18, which can effectively help the doctors follow up high-risk cases among women with high-grade cervical lesions. Cobas 4 800 HPV test is expected to be a new method for cervical cancer screening.

目的通过细胞涂片检测乳腺癌ER、PR及HER-2的过度表达与术后组织病理切片比较,探讨其应用于临床晚期患者的可行性。方法细针针吸液基薄层涂片（TLC）、免疫细胞化学方法（ICC）和术后组织病理切片的免疫组织化学（IHC）比较。计算准确率、敏感度、特异性、阳性预见值、阴性预见值、假阳性率、假阴性率等。结果检测免疫细胞化学TLC标本205例,满意标本ER为195例;PR194例;HER-2为202例,脱片均有2例,占1.0%。170例有组织病理学结果对照。ER阳性表达率:IHC为60.0%,ICC为58.5%（P=0.765）;PR阳性表达率:IHC为70.6%,ICC为59.3%（P＜0.05）;HER-2阳性表达率:IHC诊断准确性为57.5%,ICC为38.1%（P＜0.05）。乳腺癌在51～61岁年龄组例数最多（59例,占32.3%）,淋巴结转移占50.8%;其次为40～50岁组（51例,占27.9%）,淋巴结转移占47.1%;29～39岁年龄组例数最少（16例,占8.7%）,但有14例发生淋巴结转移,占87.5%。本组病例ER+/PR+/HER-2在大于73岁年龄组表达率最高,为8.7%,随着年龄的递减表达率降低,29～39岁年龄组表达率仅为0.5%,这和临床表现及细胞形态是一致的。与组织病理学IHC结果比较准确率、敏感度、特异性、阳性预见值、阴性预见值、假阳性率、假阴性率。ER分别为93.8%（Kappa=0.867）、94.1%、93.2%、96.0%、90.2%、2.5%和3.8%;PR分别为88.1%（Kappa=0.722）、88.5%、87.0%、94.3%、75.5%、3.8%和8.2%;HER-2分别为80.2%（Kappa=0.616）、67.7%、97.2%、97.0%、69.0%、1.2%和18.6%。结论细胞学ICC检测ER、PR及HER-2的过度表达,与组织学IHC比较,其准确率高,一致性好。当组织学标本难以取得时,可以考虑用细针穿刺标本检测ER、PR的表达。涂片检测受体应注意肿瘤细胞的异质性。HER-2结果的评判不应与组织学等同,细胞学可以作为筛选,阳性者宜进一步做FISH检测。