宫颈癌筛查系统及液基细胞学检测在宫颈病变筛查中的对比研究

目的:探讨宫颈癌筛查系统(TruScreen)与液基细胞学检测(liquid-based cytologytest,LCT)在宫颈病变诊断中的临床意义。方法:对487例患者行TruScreen、LCT检查,以阴道镜下病理学检查为金标准。比较两种方法的敏感度、特异度及假阴性率。结果:TruScreen、LCT阳性结果分别为229例和42例,病理学检查阳性结果为30例。Tru-Screen、LCT及TruScreen联合LCT检测的敏感度分别为73.3%、46.7%和90%,特异度分别为54.7%、93.9%和50.5%,假阴性率分别为26.7%、53.3%和10%。TruScreen及Tr-uScreen联合LCT检查敏感度高于LCT,差异有统计学意义(P<0.05),TruScreen与Tru-Screen联合LCT检查的敏感度无统计学差异(P>0.05)。结论:本研究中,TruScreen的效果评价高于LCT。在我国,TruScreen作为一种新的宫颈病变筛查技术可能会达到较好的筛查效果。     

A cervical smear review in women developing cervical carcinoma with particular reference to age, false negative cytology and the histologic type of the carcinoma

A review of all available cervical smears from 96 women who subsequently developed invasive cervical carcinoma was undertaken. The aim of the study was to determine the incidence of confirmed negative smears prior to the histologic diagnosis of carcinoma and investigate the relationship between the duration and grade of smear abnormality, the patients' age and the histologic types of cervical carcinoma. The results indicate that only 10% of women had confirmed negative smears, the majority occurring more than 7 years before the diagnosis of carcinoma. In contrast, 89% of young women (under 40 years of age) had a significant abnormality (moderate dyskaryosis or worse) up to 6 years before diagnosis. There is evidence to suggest that the preinvasive phase of cervical carcinoma may be shorter in younger women and that the less common types of cervical carcinoma occur more frequently in this group. The combination of inadequate clinical follow up and false negative cytology may have allowed a significant proportion of these women to develop invasive cervical carcinoma. Possible reasons for false negative smears have been identified and methods aimed at decreasing their frequency are discussed.     

妇产科门诊异常宫颈涂片的管理及3233例分析

目的建立并完善妇产科门诊异常宫颈细胞涂片管理制度。方法对2005年1月1日至2006年12月31日在北京大学第三医院妇产科门诊行宫颈液基细胞学涂片的患者中,结果为不能明确意义的不典型鳞状细胞及以上患者3233例,依据美国阴道镜与宫颈病理协会推荐的异常宫颈涂片处理指南进行处理,并行回顾性分析。结果3233例异常宫颈涂片患者中行阴道镜检查1275例,其中67.6%的高危型HPVDNA阳性的不能明确意义的不典型鳞状细胞、68.9%的不能除外高度鳞状上皮内病变的不典型鳞状细胞、72.9%的低度鳞状上皮内病变、80.2%的高度鳞状上皮内病变患者行阴道镜检查,通过加强对异常宫颈涂片的管理,2006年比2005年有更高比例的宫颈涂片患者在本院行阴道镜检查,共检出宫颈上皮内瘤变2级及以上病变(CIN2 )243例。结论加强异常宫颈细胞学涂片的管理在宫颈防癌筛查工作中有重要意义。     

宫颈癌医院机会筛查与社区筛查相关因素分析

目的分析宫颈癌医院机会筛查和社区筛查的相关因素。方法对2008年1月至2008年12月在北京市垂杨柳医院妇科门诊行宫颈癌机会筛查和社区筛查妇女的相关因素进行分析,其中门诊机会筛查7223例（机会筛查组）,社区筛查11539例（社区筛查组）。结果社区筛查组年龄[（45.75±9.29）岁]大于门诊机会筛查组[（33.55±10.49）岁],其中社区筛查组年龄〉50岁者占39.8%,初中及以下文化程度者占96.2%,两组筛查妇女年龄比较,差异有统计学意义（P〈0.001）。两组宫颈鳞状上皮内低度病变所占比例（机会筛查组1.2%;社区筛查组0.4%）比较,差异有统计学意义（P〈0.001）;机会筛查组鳞状上皮内高度病变及宫颈癌发生率高于社区筛查组,但差异无统计学意义（P〉0.05）。机会筛查组不同级别的宫颈上皮内瘤变（CIN）和宫颈癌的检出率均高于社区筛查组,差异有统计学意义（P〈0.05）。结论社区筛查人群年龄较大,文化程度低,应重视这一群体防癌知识宣教,提高筛查率。宫颈癌医院机会筛查与社区筛查同样重要。     

Urine cytology as a screening test for bladder infiltration in cervical cancer

Ultrasound is currently used as a screening test for bladder infiltration in patients with advanced-stage cervical cancer at our institution. Cystoscopy is reserved for patients with abnormal bladder ultrasound findings. This study was undertaken to reevaluate this policy and to compare the results of different screening tests. The study was carried out in Pretoria academic complex. All newly diagnosed cervical carcinoma patients stage II and above were included in this study. The standard staging investigations were done on all patients. In addition, urine midstream and catheter specimens were sent for cytology. Cystoscopy and biopsy were performed on all patients. Two hundred twenty-eight patients were enrolled into this study. At cystoscopy, 47 patients had bladder mucosa suspicious of malignant infiltration, of which 17 had bladder mucosa infiltration diagnosed on histology. Urine catheter cytology has a sensitivity of 94% and specificity of 82% for bladder mucosa infiltration. The predictive value of a positive test is 31% and for a negative test is 99%. Catheter urine cytology is a very useful screening test for bladder infiltration in patients with cervical cancer. Cystoscopy should be reserved for patients with abnormal urine cytology in resource-poor settings with a large burden of disease.     

Screening history in women with cervical cancer in a Danish population-based screening program

Objective.

The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer.

Methods.

The study describes the results of a quality control audit, performed on all new cervical cancer cases diagnosed in the years 2008-2009 at two major Danish screening-centers. All relevant cytological and histological cervical samples were reviewed.

Results.

202.534 cytological samples were evaluated in the study period, while 112 women were diagnosed with cervical cancer. The histological diagnoses comprised: 62 (55.4%) squamous cell carcinomas, 20 (17.9%) microinvasive squamous cell carcinomas, 25 (22.3%) adenocarcinomas and 5 cancers of different histology. The mean age of study subjects was 46.6 years. 51 (45.5%) women had deficient screening histories, while 45 (40.2%) women had followed the screening recommendations and had normal cervical samples in review. 11 (9.8%) women were diagnosed with false negative cytology, 2 women had false negative histological tests, while pathological review was not feasible for 3 subjects.

Conclusions.

More than 45% of the cervical cancer cases in our study were due to deficient cervical screening, stressing the importance of increasing the screening-uptake and coverage. 40% interval cancers emphasize the relevance of further cervical testing of women with relevant symptoms, despite of prior normal cervical samples. Finally, 9.8% false negative cytological samples are consistent with previous reports, but still a part of the screening program that should be improved.     

Biopsy correlates of abnormal cervical cytology classified using the Bethesda system

OBJECTIVE: The goal of this study was to determine the colposcopic findings underlying cytologic abnormalities classified according to the Bethesda system. METHODS: Women undergoing colposcopy for abnormal cytology at an urban teaching hospital between July 1, 1996 and December 31, 1999 had Papanicolaou smears repeated. Results were compared both with biopsy histology and with the worst histology reported after 8-26 months of follow-up. kappa statistics and Spearman's rho were calculated to determine the degree of agreement. RESULTS: Colposcopy was performed for 2263 (94%) women. Referral and repeat Pap smears were reported identically in 493 (25%) of the 1962 women with results for both. No AGUS (atypical glandular cells of uncertain significance) smears were confirmed on repeat smear, and after excluding AGUS, agreement within one grade was found in 1305 of 1854 (70%). Among the 1842 women with squamous cytologic abnormalities, biopsy revealed a lesion more severe than that suggested by referral cytology in 577 (31%) and a less severe lesion in 648 (35%); exact correspondence was found in only 646 (35%). Of 317 women with ASCUS (atypical squamous cells of uncertain significance) on referral Pap smear, a negative repeat smear, and a specific biopsy result, 95 (30%) had true negative histology, while 148 (47%) had condyloma, 56 (18%) had cervical intraepithelial neoplasia (CIN) 1, 8 (3%) had CIN 2, 10 (3%) had CIN 3, and none had cancer. Comparison of repeat smear and colposcopic biopsy yielded a kappa statistic of 0.16. CONCLUSIONS: Cytology classified according to the Bethesda system does not accurately predict histologic diagnosis.     

Histologic findings from the cervix among older women with abnormal cervical cytology

OBJECTIVE: The aim of this study was to determine rates of cervical neoplasia among women at least 50 years of age referred for colposcopy after abnormal cytology and to compare these to younger women. METHODS: From a prospectively accrued database of 2825 women undergoing colposcopy in the gynecology clinic of an urban public hospital, women at least 50 years of age with a known cytologic abnormality were selected for retrospective analysis. Demographic and medical information collected at colposcopy and subsequent histology was reviewed. Cytology results were based on the Bethesda system, and histology was reported as grades of cervical intraepithelial neoplasia (CIN). Statistical analysis was by t test, chi(2) test, and Mann-Whitney U test. RESULTS: Among 325 women at least age 50, cervical histologic results were benign or atypical for 147 (45%), CIN1 for 28 (9%), CIN2 for 21 (6%), CIN3 for 49 (15%), cancer for 11 (3%), and ungraded dysplasia for 7 (2%), with no biopsy performed for 62 (19%) women. Symptoms were more common among women with cancer (6/11 or 55%) than those without (62/263 or 21%, P = 0.01). Negative histology (80/231 or 35%), CIN3 (49/231 or 21%), and cancer (9/231 or 4%) were more common among older than younger women (287/1403 or 20%, 199/1403 or 14%, and 11/1403 or 1%, respectively), while atypia (438/1403 or 31%), CIN1 (321/1403 or 23%), and CIN2 (147/1403 or 10%) were more common among younger than older women (53/231 or 23%, 23/231 or 10%, and 17/231 or 7%, respectively, P < 0.04). Differences in the distribution of cervical histology results remained significant among women with ASCUS (P = 0.001) but not those with LSIL (P > 0.9), HSIL (P > 0.07), or cancer (P > 0.4). CONCLUSIONS: Most older women are referred for colposcopy with lesser grades of abnormality, but cervical cancers are found across all cytologic grades and were more common in symptomatic women. Compared to younger women with abnormal cytology, women at least 50 years of age with ASCUS had higher rates of negative evaluations and high grade but not low- or mid-grade lesions.     

A comparison of liquid-based cytology with conventional cytology.

OBJECTIVE: To evaluate the 2 methods of cytologic screening to detect abnormalities of the cervical epithelium. METHODS: This study with 3 groups of women was performed at Selcuk University Meram Medical School between January 2004 and March 2006. In one group (paired sample for specimen collection) women were screened with conventional cytology; in another group (paired sample for specimen collection) they were screened with liquid-based cytology; and in the third group (split sample for specimen collection) they were screened by both methods. RESULTS: The rate of unsatisfactory results was lower in the liquid-based than in the conventional cytology group (6.1% vs. 2.6%; P<0.05). More smears containing atypical squamous cells of undetermined significance were detected by the liquid-based method, but the difference was not statistically significant. Also, no statistically significant differences between liquid-based and conventional cytology were observed in the detection of other epithelial abnormalities (P>0.05). CONCLUSION: The liquid-based and conventional cytology methods were found to be equivalent in the detection of cervical epithelial abnormalities.     

Correlation of endocervical curettage with subsequent cone biopsy in the investigation of abnormal cervical cytology

Abstract. Endocervical curettage and cone biopsy found no high-grade intraepithelial lesions in premenopausal women who had a satisfactory colposcopic evaluation with low-grade cytology and exocervical biopsies.
A retrospective analysis was performed of patients who underwent cervical cone biopsy to investigate an abnormal cytology. The histology of the cone was compared with the cervical cytology and the ectocervical biopsies. Over a 6-year period, 346 cone biopsies were performed at the UCLA Medical Center. Of these, 338 cone specimens were available for review, 279 had complete colposcopic records, and 227 had both an endocervical curettage and ectocervical biopsy. No premenopausal patients with low-grade cytology, satisfactory colposcopy and a low grade lesion on ectocervical biopsy subsequently had a high-grade lesion or invasive cancer on the cervical cone biopsy. Thus, in these patients the endocervical curettage did not prove to be of diagnostic value. In contrast, five patients with high-grade cytology, satisfactory colposcopy and low-grade ectocervical lesions had positive endocervical curettages and high-grade lesions on cone biopsy. These data suggest that selective use of endocervical curettage in premenopausal patients with satisfactory colposcopy can be based on whether the cytology is low grade or high grade. In premenopausal patients with low-grade cytology and satisfactory colposcopy, endocervical curettage can be omitted, while any patient who has a high-grade cytology should have an endocervical curettage.     

Cytology alone versus cytology and cervicography for cervical and cervicography for cervical cancer screening: a randomized study. European Society for Oncological Research

OBJECTIVE: To compare the ability of combined cytology and cervicography with cytology alone to decrease the number of premalignant cervical lesions found in subsequent screening. METHODS: Five thousand five hundred fifty women 18-91 years old were randomized to cytology plus cervicography or cytology alone. One year later, women were rescreened using both cytology and cervicography. All women with positive lesions were referred for colposcopically directed biopsies and treatment as indicated. We expected to decrease by half the number of cervical intraepithelial neoplasia (CIN) lesions at 1-year screening by adding cervicography to cytology at initial screening. RESULTS: Compared with cytology screening alone, screening with cytology plus cervicography showed a 30% reduction in CIN I-II-III cervical lesions at 1-year screening round (relative risk [RR] 0.70; 95% confidence interval [CI] 0.32, 1.55, P = .35) and a 43% reduction in CIN II-III cervical lesions (RR 0.57; Cl 0.14, 2.16, P = .36). Most lesions detected by one test were not detected by the other. In a retrospective search, nine biopsies (one normal and eight revealing CIN I or more on histopathology) were found to be positive for the human papillomavirus; five of the nine biopsies were found by cytology, three by cervicography, and one by both tests. CONCLUSION: The addition of cervicography to cytology in initial screening did not significantly decrease the number of premalignant cervical lesions detected 1 year later, probably because of the transient nature of most of these lesions. Because cytology and cervicography seemed to detect different premalignant lesions, it is possible that cervicography could detect lesions that do not express the cellular abnormalities necessary for detection by cytology.     

The evaluation of human papillomavirus DNA testing in primary screening for cervical lesions in a large Japanese population

To examine the utility of human papillomavirus (HPV) DNA testing for the screening of cervical cancer and its precursors, a prospective cohort study was performed in which a total of 8156 women with a median age of 36 years were enrolled. Two smear samples scraped from the uterine cervix were served for Papanicolaou test and HPV DNA testing (Hybrid Capture-II system). HPV-positive samples were further examined for HPV subtype using a DNA microarray chip. Women with cytologic abnormality or those with high-risk HPV DNA were further examined by colposcopy to determine histologic diagnosis. High-risk HPV DNA was detected in 11% of the general population, with higher prevalence of specific types, including 52, 16, 58, 51, 56, and 18. As expected, younger women were likely to have increased frequency of HPV infection. Notably, HPV DNA testing detected all 45 cases of cervical intraepithelial neoplasia (CIN) 3, while cytologic findings were negative in 6 of these cases. It is of particular interest that CIN was commonly associated with multiple HPV types, while invasive cancers had a single type of HPV. In terms of both sensitivity and positive predictive value in detecting the CIN, HPV DNA testing is superior to cytology. However, most importantly, HPV DNA testing in combination with cytology significantly improved the efficacy to CIN screening.     

Acetic-acid guided visual inspection vs. cytology-based screening for cervical cancer in the Philippines.

OBJECTIVES: To compare the validity and acceptability of acetic-acid visualization (VIA), magnified acetic-acid visualization (VIAM), spatula+cotton swab-Papanicolaou (Pap) smear (SS), and cervical brush-Pap smear (CB) in the detection of precursor/early cervical cancer lesions. METHODS: A total of 12992 women aged between 25 and 65 years from 14 Philippine centers were randomly allocated to the four tests. The gold standard was colposcopy with biopsy for positive/suspicious cases. RESULTS: Sensitivity rates [95% confidence intervals (CIs)] were 37 (CI, 26.8-48.5), 34.1 (CI, 24.8-44.8), 14.3 (CI, 6.4-27.8), and 19.1 (CI, 9.2-34.6) for VIA, VIAM, SS, and CB, respectively. Specificity rates were 90.7 (CI, 89.6-91.7), 90.7 (CI, 89-91.1), 97.5 (CI, 96.8-98), and 97.9 (CI, 97.3-98.4), respectively. Kappa for the Pap smear (PS) within centers ranged from -0.154 to 0.783, and between centers from -0.028 to 0.364. Screeners preferred CB; screened-women preferred VIA. CONCLUSIONS: The acetic-acid visualization and VIAM methods are recommended for initial cervical cancer screening in the Philippines.     

Adoption of HPV testing as an adjunct to conventional cytology in cervical cancer screening in Japan

Objective

To assess the effectiveness of including HPV testing as an adjunct to conventional cytology in cervical cancer screening.

Methods

Atypical epithelial cells (ATC) were classified according to the 2001 Bethesda classification system. The study ran for 6 years from May 2004 to November 2009 in conjunction with public cervical cancer screening for Kanazawa City residents. Patients with ATC (ASC-US, ASC-H, and AGC) underwent parallel testing for high-risk HPV types with the Hybrid Capture II system; HPV positive and cytology-ATC cases were recalled for colposcopic examination and biopsied if necessary. Results were compared with those obtained before HPV screening was initiated.

Results

A total of 62 645 women underwent screening over the 6-year period; of these, 3622 (5.8%) were ATC positive, among whom 527 (14.5%) tested HPV-positive. These 527 women (0.8% of the screened population) were recalled for colposcopic examination. The resulting 426 biopsies were diagnosed as CIN 1 (n = 187), CIN 2 (n = 53), CIN 3 (n = 11), and invasive cervical cancer (n = 2).

Conclusion

HPV testing as an adjunct to conventional cytology in cervical cancer screening seems to increase detection sensitivity with proven cost-effectiveness.     

A multicentre study comparing cervicography and cytology in the detection of cervical intraepithelial neoplasia

Objective To evaluate in a multicentre setting the performance of cervicography compared with
Design Prospective comparative multicentre study.
Setting Three hospitals with outpatient gynaecology clinics and three cancer screening clinics.
Participants and methods Cervical cytology and cervicography were performed on 5724 women. If one or both tests showed an abnormality suggestive of at least a low grade squamous intraepithelial lesion, a colposcopy with directed biopsy was carried out. Cervicograms were evaluated by four experienced 'senior' assessors and by ten new 'junior' assessors.
Results Results were fully analysed for 5192 women (9l%). A cervical biopsy was carried out on 228 women and this confirmed a true positive lesion in 116 cases (incidence rate: 2.2%). Of these, 72 cases (62.1%) were detected by cervicography and 64 (55.2%) by cytology. This difference was not statistically significant (McNemar:   P = 0.475  ). Only 20 cases of CIN (17%) were concordantly detected by both tests. Senior assessors performed significantly better with a detection capacity of 80.6% compared to a detection capacity of 56.6% for the junior assessors (χ² test:   P = 0.034  ).
Conclusions Cervicography must be considered as a complementary test to cytology. Overall detection of CIN is improved, but this is mainly due to the detection of more low grade lesions. The lower sensitivity and specificity in high grade lesions compared with cervical cytology is the main limitation of cervicography in screening for CIN. An important finding was that the performance of cervicography was highly dependent on the assessors' experience.