Factors contributing to false‐negative and potential false‐negative cytology reports in SurePath™ liquid‐based cervical cytology

N. Gupta, D. John, N. Dudding, J. Crossley and J. H. F. Smith
Factors contributing to false‐negative and potential false‐negative cytology reports in SurePath ? liquid‐based cervical cytology Objectives: The characteristics of false‐negative conventional cervical cytology smears have been well documented, but there is limited literature available for liquid‐based cytology (LBC), especially SurePath? samples. We aimed to assess the characteristics of false‐negative SurePath LBC samples. Methods: Over a period of 5 years, an audit of false‐negative reports in SurePath cervical cytology was undertaken. In a workload of 183, 112 samples, 481 (0.3%) false negatives were identified using two routes: those detected by routine laboratory internal quality control (rapid pre‐screening) (n = 463) and those reported as normal (true false negatives) with concurrent high‐grade cervical histology (n = 18). Ninety‐five false‐negative cases with a subsequent biopsy reported as at least cervical intraepithelial neoplasia grade 2 (CIN2+) were reviewed for a number of different cytomorphological features. Results: Of 95 samples with subsequent CIN2+, 30.5% predominately contained microbiopsies/hyperchromatic crowded cell groups (HCGs), 27.3% sparse dyskarytotic cells, 4.2% pale cell dyskaryosis, 6.3% small dyskaryotic cells; 3.2% were misinterpreted cells, 8.4% contained other distracting cells, 7.4% were low contrast, 5.3% were unexplained and 7.4% were true negatives. The mean number of microbiopsies/HCGs in that category was 4.6. The mean number of abnormal cells in the sparse dyskaryotic cell category was 13.8. Conclusions: Microbiopsies/HCGs were the commonest reason for false negatives. They were usually present in sufficient numbers to be detected but interpretation could be problematic. Dispersed single abnormal cells were usually not identified because of their scarcity or the presence of distracters.     

Analysis of the performance of 100% rapid review using an average time of 1 and 2 minutes according to the quality of cervical cytology specimens

E. J. C. Manrique, N. L. A. Souza, S. B. N. Tavares, Z. B. P. Albuquerque, L. C. Zeferino and R. G. Amaral Analysis of the performance of 100% rapid review using an average time of 1 and 2 minutes according to the quality of cervical cytology specimens Objectives: To compare the performance of the 100% rapid review method carried out in a mean time of either 1 or 2 minutes according to cytological final result, and to assess whether the presence of obscuring factors in cervical smear samples affects the frequency of false‐negative results. Methods: A total of 5 235 smears classified as negative (93.0%) or unsatisfactory (2.1%) at routine screening were submitted to 100% rapid review using mean times of 1 and 2 minutes. Results: Of the 5 235 smears submitted to 1‐minute rapid review, 88 were considered suspect and of these, 45 were confirmed as abnormal in the cytological final result. When the time used was 2 minutes, 67 smears were considered suspect, 44 of which were confirmed as abnormal. Sensitivity and specificity were similar in the 1‐ and 2‐minute reviews. In smears in which samples were satisfactory and had no obscuring factors, sensitivity and specificity were 64.2% and 98.9% and 61.5% and 99.5% for the 1‐ and 2‐minute reviews, respectively. In comparison, in smears in which the sample was satisfactory for analysis but partially obscured (50–75%), sensitivity and specificity were 64.7% and 99.9% and 70.6% and 99.8% for the 1‐ and 2‐minute reviews, respectively. Conclusions: The method of rapid review of 100% showed no difference in the detection of false‐negative results using the time of 1 or 2 minutes. The quality of the sample did not influence the detection of false‐negatives.     

Colposcopic assessment of the accuracy of cervical cytology screening

Two hundred asymptomatic women in a general practice were screened both cytologically and colposcopically for evidence of cervical intraepithelial neoplasia. The prevalence detected by cytology alone was 5%, but the prevalence detected by cytology and colposcopy together was 11%. None of the larger lesions of cervical intraepithelial neoplasia (affecting more than two quadrants of the cervix) was associated with negative cytology. The false negative cytology rate for smaller lesions was 58%.The clinical importance of the smaller lesions that were not accurately detected by cytology screening is unknown. As these lesions affected 6% of the screened population further studies of their clinical course are urgently required. Local destructive treatment in such cases may represent considerable overtreatment. If these lesions prove to be clinically important, however, the results of this study predict an increasing epidemic of preinvasive and invasive disease of the cervix.     

Human papillomavirus DNA and liquid-based cervical cytology cotesting in screening and follow-up patient groups

OBJECTIVE: To compare the use of human papillomavirus (HPV) DNA and cervical cytology cotesting in screening and follow-up of patients with previous cervical abnormalities and to assess the significance of a positive HPV DNA test result in re-screening of cytologically normal cases. STUDY DESIGN: Cellular samples collected in liquid-based fixative were used for both cervical cytology and HPV DNA testing. The cervical cytology slides were manually screened by cytotechnologists followed by rapid re-screening by pathologists. The HPV DNA tests were performed using hybrid capture test kits. Statistical analyses of cervical cytology results and HPV DNA tests for high- and low-risk HPV from both patient groups were carried out. RESULTS: The prevalence of HPV DNA-positive cases was higher in younger patients. There was a poor correlation between cervical cytology results and HPV DNA tests for the screening group (kappa = 0.23), but a fair to good correlation was obtained for the follow-up group (kappa = 0.51). The false negative fraction of cytology negative/HPV DNA positive cases (0.1317), as compared with cytology negative/HPV DNA negative cases (0.0056), was statistically significant (p = 0.000001). CONCLUSION: The prevalence of HPV DNA decreased with increasing age in both the screening and follow-up patient groups. Virus clearance was delayed in the follow-up group as compared with the screening group. There was a poor correlation between cervical cytology and HPV DNA tests in the screening group but a fair to good correlation in the follow-up patient group. Cotesting of HPV DNA and cervical cytology increases the sensitivity and decreases the false negative fraction, suggesting that cotesting could be used to increase the interval of screening.     

Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer

OBJECTIVE: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma. STUDY DESIGN: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer. RESULTS: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions. CONCLUSION: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.     

Laboratory performance measures: evidence against low-risk women explaining low detection rates of high-grade abnormalities

OBJECTIVE: When a laboratory has a low reporting rate of high-grade abnormality for its cervical cytology specimens, the question arises whether this is due to the laboratory screening a low-risk group of women. This study was undertaken to explore the hypothesis that a low-risk group of women were screened by Victorian laboratories not meeting the recommended minimum standard for the detection of high-grade abnormalities. METHODS: A cohort of 28 094 women was established comprising women whose cervical cytology was reported in 2000 by laboratories not meeting the recommended standard of 0.5% high-grade abnormalities in their reporting of community smears. Outcome measures included the prevalence of high-grade abnormality on the next cytology test for the women, the positive predictive value of the cytology reports of high-grade abnormality, and the standardized incidence ratio for a later diagnosis of cervical cancer. RESULTS: The prevalence of high-grade abnormality was 0.36% on the index cytology compared with 0.68% on the first subsequent cytology report. Sixty-nine per cent (60/87) of the index cytology reports of high-grade abnormality were confirmed as high-grade abnormalities on histology, compared with 70.8% (121/171) for the first subsequent reports of high-grade abnormality. During 70 015 person-years at risk, nine cases of cervical cancer were observed compared with 5.21 expected cases, giving a standardized incidence ratio of 1.73 (95% CI 0.79-3.28). CONCLUSIONS: These results do not support a hypothesis that the low detection rate for high-grade abnormalities is due to the women comprising a low-risk group for cervical neoplasia.     

Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in screening for bladder cancer? – experience at Kuwait University

Objectives:  This prospective study was undertaken to evaluate nuclear matrix protein (NMP22) compared to urine cytology in the detection of bladder cancer and also to determine whether indexing suspicious cytology to NMP22 could enhance the clinical utility of cytology.
Methods:  Cytological findings of voided urine collected prior to a cystoscopic biopsy were correlated with urine NMP22 assay in 46 patients attending the urology clinic in Mubarak Al-Kabeer Hospital. The patients were clinically categorized into newly diagnosed cases of transitional cell carcinoma (TCC), recurrent TCC, TCC in remission and controls.
Results:  Using histological diagnosis as the gold standard the sensitivity and specificity of NMP22 were 78% and 43% respectively and of cases with malignant urine cytology were 30% and 87% respectively. If suspicious and malignant cytology were combined as positive results the sensitivity increased significantly to 87% while the specificity decreased but not significantly to 74%. Suspicious or malignant cytology enhanced by positive NMP22 gave a sensitivity of 70% and specificity of 87% neither of which was significantly different from cytology alone. There were three false positive cases on cytology and 13 false positive cases on NMP22 assay. There were three false negative cytology and five false negative NMP22 cases but only one was false negative for both, resulting in a high sensitivity (96%) but low specificity (30%) if either positive NMP22 or malignant or suspicious cytology was taken as a positive result.
Conclusion:  Combining NMP22 with malignant or suspicious cytological result improved sensitivity for the detection of bladder cancer but with a major decrease in specificity, suggesting a potential role in screening rather than diagnosis.     

O-9AUDIT ON BK VIRUS DETECTION IN RENAL TRANSPLANT RECIPIENTS

Introduction and Aims:  The sensitivity of bronchial cytology (brushings, washings) is in the region of 70–80%. Therefore a significant number of false negatives occur. The main aims of this study were to: (i) To identify negative bronchial washings and brushings performed in 2004 with malignant follow-up and (ii) To ascertain the cause of the false negative result where possible. 56 patients with negative bronchial cytology and subsequent malignant follow-up on a pulmonary specimen were identified. These cases formed the basis of the study.
Results:  In our series peripheral tumour location and specimen inadequacy accounted for the majority of false negative results. Malignant cells were missed in a minority of cases (5 of 56). An explanation for failure of diagnosis in 4 of the 5 cases was paucity of malignant cells. In one case of small cell carcinoma, malignant cells were abundant, but were not recognized.
Recommendations:  What can be done to reduce the false negative rate?
(1) In cases where radiology has indicated that the tumour is peripherally located patients could proceed directly to fine needle aspiration.
(2) Improved communication between clinicians and pathologists is required in relation to: (a) specimen adequacy and (b) degree of clinical suspicion.     

昂丹司琼联合泮托拉唑对宫颈癌同步放化疗所致恶心呕吐的临床疗效

摘要 目的：研究昂丹司琼联合泮托拉唑对宫颈癌同步放化疗所致恶心呕吐的临床疗效。方法：选择2018年1月～2020年1月我院收治的79例宫颈癌患者,均采取同步化疗,将其随机分为两组。对照组在当天化疗前30 min和随后的6 d连续静脉注射昂丹司琼,每次8 mg,1次/d;同时给予地塞米松磷酸钠注射液10 mg,1次/d。观察组在昂丹司琼的基础上静脉注射泮托拉唑,每次40 mg,1次/d,给药的时间与昂丹司琼相同。比较两组宫颈癌患者恶心呕吐的完全缓解率、癌因性疲乏评分和不良反应的发生情况。结果：两组化疗第1、2 d恶心呕吐的完全缓解率比较差异无明显统计学意义(P>0.05),观察组化疗第3、4、5、6 d恶心呕吐的完全缓解率分别为76.92 %、79.49 %、87.18 %、87.18 %,均明显高于对照组(P<0.05);观察组的癌因性疲乏评分为(45.39±7.29)分,明显低于对照组的(67.24±8.36)分(P<0.05);两组的乏力嗜睡、便秘、椎体外系反应、失眠/不安、腹泻、轻度头痛的发生率比较无明显统计学差异(P>0.05)。结论：昂丹司琼联合泮托拉唑对宫颈癌同步放化疗所致恶心呕吐的疗效显著优于单用昂丹司琼治疗,并能明显减轻癌因性疲乏,且安全性高。     

The role of cervical cytology and colposcopy in detecting cervical glandular neoplasia

Objective:  To determine the role of cervical cytology and colposcopy in the management of endocervical neoplasia.
Setting:  Colposcopy unit and cytology laboratory in a teaching hospital.
Sample:  Group 1 included 184 smears showing endocervical glandular neoplasia from 129 patients and group 2 included 101 patients with histology showing endocervical abnormalities in a 6-year period (1993–1998). Follow-up of 6–11 years to 2004 was available.
Methods:  Group 1 were identified from the cytology computer records. Group 2 were identified from histology records on the cytology database and a record of histology cases kept for audit purposes. The clinical records were examined retrospectively.
Results:  The positive predictive value (PPV) of abnormal endocervical cells in smears was 81.1% for significant glandular/squamous [cervical glandular intraepithelial neoplasia (CGIN)/cervical intraepithelial neoplasia grade2 (CIN2 or worse)] lesions. The PPV of colposcopy was 93.5% for significant glandular/squamous lesions of the cervix. The postcolposcopy probability of a significant lesion when colposcopy was normal was 87.5%. The sensitivity of colposcopy in detecting endocervical lesions was 9.8%. The sensitivity of cervical smears in detecting a significant endocervical abnormality (CGIN or worse) was 66.3%. The false negative rate for cytology of endocervical glandular lesions was 4.0%.
Conclusions:  Endocervical glandular neoplasia detected on cytology is predictive of significant cervical pathology even when colposcopy is normal, which supports excisional biopsy in the primary assessment of these smears. The high concomitant squamous abnormality rate justifies the use of colposcopy to direct biopsies from the ectocervix. Cervical cytology is the only current screening method for cervical glandular abnormalities but sensitivity is poor.     

Genital human papillomavirus testing by in situ hybridization in liquid atypical cytologic materials and follow-up biopsies

OBJECTIVE: To describe cases of HPV testing by DNA in situ hybridization performed on atypical cervicovaginal samples collected by a liquidsed method that were negative for HPV DNA on cytology but revealed cervical intraepithelial neoplasia on follow-up biopsies. STUDY DESIGN: Three hundred ninety-five consecutive SurePath atypical squamous cells of undetermined significance (ASC-US) cytologic samples from asymptomatic, reproductive-age women were tested for human papillomaviruses (HPVs) by the in situ hybridization (ISH) method (Ventana Inform HPV Test, Tucson, Arizona, U.S.A). One hundred (25%) cases underwent follow-up colposcopic biopsy within 3 months of cytology. All the tests (cytology, ISH, histology) were independently evaluated without knowledge of the other tests. RESULTS: One hundred twenty-two (33%) cytologic samples were positive for HPVs. Of a total of 100 (HPV positive and negative) follow-up biopsies, 55 were positive for cervical intraepithelial neoplasia (CIN). Fourteen cases of biopsy-proven CIN tested negative for all HPV types in the prior cytologic samples. Retesting of the 14 CIN tissues by ISH was negative in 10, positive for HPV in 2 and inconclusive in 2. CONCLUSION: There is a small but significant (14%) false negative rate with HPV testing by the Ventana ISH method. Clinically suspicious cases should be followed even if an HPV test is negative.     

Brush cytology of colorectal malignancies

OBJECTIVE: To evaluate the specificity and sensitivity of brush cytology and biopsy in colorectal malignancies. STUDY DESIGN: The study was performed over 3 years, 1998-2000. Seventy-six patients with any colorectal lesion on colonoscopy were selected, and in all of them brush cytology and biopsy were done at the same time. The cytologic smears and biopsies were reviewed separately. The cytologic smears were categorized as negative, suspicious, suggestive or positive for malignancy. The results of cytology and biopsy were compared based on sensitivity and specificity. The gold standard for positive cases was the tissue specimen after surgery; negative cases were followed for at least 1 year. Cases with 1 year of disease-free survival were considered negative. RESULTS: Among 76 cases, 4 were excluded because of unsatisfactory cytologic smears. Of the remaining 72 cases, 31 were male and 41 female. The age range was 19-80 years. Cytology showed 23 positive and 49 negative cases (1 false positive and 3 false negative). Biopsy showed 24 positive and 48 negative cases (no false positives and 1 false negative). There were 47 negative cases, followed for at least 1 year, and after that we considered them definitively negative for malignancy. Sensitivity of cytology and biopsy was 88% and 96%; specificity was 98% and 100%, respectively. Combined use of brush cytology and biopsy had the highest sensitivity, 100%. CONCLUSION: Brush cytology of the colon is a safe, fast and reliable method for the diagnosis of colorectal cancer. We recommend performing it in conjunction with biopsy. It is also reasonable to perform a repeat biopsy in patients with negative biopsy and positive cytology for a definitive diagnosis.     

Prospective parallel randomized trial of the MultiCyte™ ThinPrep® imaging system: the Scottish experience

T.J. Palmer, S.M. Nicoll, M.E. McKean, A.J. Park, D. Bishop, L. Baker and J.E.A. Imrie
Prospective parallel randomized trial of the MultiCyte? ThinPrep^® imaging system: the Scottish experience Background: Computer‐assisted screening of cervical liquid‐based cytology (LBC) preparations using the ThinPrep® Imaging System (TIS) has shown improved qualitative and quantitative gains. The use of Multicyte? has not been described in a well‐established national screening programme with a low incidence of high‐grade dyskaryosis. Objectives: To assess the impact of computer‐assisted screening within the Scottish Cervical Screening Programme (SCSP). Methods: Two groups of three laboratories, each sharing a ThinPrep® Imager, screened 79 366 slides randomized to test and 90 551 to control arms by laboratory accession. Screeners were not blinded. Standard laboratory reporting profiles of the SCSP, sensitivity, specificity and false‐negative rates of all grades of LBC abnormalities with respect to final cytology reports, predictive value for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on histology; and screening rates were compared for both arms. Results: Inadequate and negative reporting rates were significantly lower and low‐grade reporting rates significantly higher in the imager arm. Imager‐assisted screening showed significantly better specificity than manual screening with respect to the final cytology result. There was no evidence of a significant difference in the detection of CIN2 + or CIN3 + . Positive, abnormal and total predictive values (high‐grade, low‐grade and all abnormal cytology found to be CIN2 + , respectively) were similar in both arms. Productivity was significantly higher in the imager arm. Conclusion: Computer‐assisted screening in a well established screening programme showed significantly improved productivity without loss of quality. These findings should inform future policy for cervical screening programmes.     

Review of cervical smears from 76 women with invasive cervical cancer: cytological findings and medicolegal implications

OBJECTIVE: To review cervical smears from 76 women which were taken prior to the diagnosis of invasive cervical cancer and to determine the appropriateness of the cytology reports issued on the smears. METHODS: Cervical smears, clinical records, cervical smear history and cytology reports from 76 women with invasive cervical cancer were reviewed. After microscopic review of the cervical smears, the cases were divided into two groups: Group 1 comprised 50 women who were found to have had at least one false-negative (F/N) smear report prior to the diagnosis of invasive cervical cancer. Group 2 comprised 26 women for whom no evidence of F/N reporting was found. RESULTS: A total of 209 cervical smears from the 50 women in group 1 were available for review (range 2-12 smears per woman); 100 of the 209 smears were considered to have been reported appropriately. Ninety-seven smears which had been reported originally as negative or inadequate were found, on review, to contain numerous severely dyskaryotic cells and were reclassified as F/N smears. All of the 50 women had at least one F/N smear and 29 had two or more. Twelve smears from eight women contained only a few (<200 severely dyskaryotic cells). Forty women developed invasive squamous carcinoma and 10 developed invasive adenocarcinoma. The stage at diagnosis ranged from 1A to stage 4. Seventy-one smears from the 24 women in group 2 were available for review (range 1-15 smears per woman). In two cases included in group 2, no smears were provided for review as the smears had been lost or mislaid. Review of the 71 smears confirmed the accuracy of the original cytological classification of the smear. Nineteen women were diagnosed with squamous cancer, two microinvasive cancer, one glassy cell, two adenocarcinomas, and one with adenosquamous carcinoma. One women was found to have an embryonal rhabdomyosarcoma of the corpus uteri involving the cervix. DISCUSSION/CONCLUSION: The medicolegal implications are discussed in the light of the above findings. Evidence of breach of duty of care was presented in all 50 cases in group I although causation was not established in every case. There was no evidence of failure of duty of care in terms of the standard of the cervical cytology reports issued or standard of clinical management in 17 of the 26 cases in group 2. However, in seven of the 26 cases in group 2, clinical management of the case was substandard due to failure to investigate symptoms of irregular bleeding regardless of a negative cytology report (two cases), failure to act upon a suspicious smear report or consecutive inadequate smear reports (two cases), failure of follow-up after treatment of CIN3 (two cases) and histological misdiagnosis (one case).     

Comparison of conventional Papanicolaou smear and SurePath® liquid-based cytology in the Copenhagen population screening programme for cervical cancer

OBJECTIVE: To compare diagnostic performance of conventional Papanicolaou smear with SurePath liquid-based cytology in a population screening programme. METHODS: A retrospective comparison was performed on data from two 18-month periods of the screening programme for cervical cancer in the municipality of Copenhagen with conventional Papanicolaou technique (n = 82,116) and liquid-based cytology (n = 84,414). RESULTS: After the conversion to liquid-based cytology the percentage of unsatisfactory samples decreased from 2.3% to 0.3% (P < 0.001), whereas the number of normal cervical samples lacking an endocervical component increased from 8.5% to 8.9% (P < 0.005). The percentage of samples with atypical cells and cells suspicious for malignancy increased from 3% to 4.2% (P < 0.001) and from 1.9% to 2.4% (P < 0.001), respectively. The subsequent histological follow-up showed normal findings decreased from 70.5% to 68.9% and from 28.0% to 26.1%, respectively. However, in relation to the entire screening populations, there was an increase of normal findings from 2.12% to 2.89% after primary atypical diagnosis and from 0.53% to 0.62% after diagnosis of suspicious cells after conversion to the liquid-based technique. CONCLUSIONS: This study showed the number of unsatisfactory samples to be significantly reduced with the liquid-based technique. The data suggest that there is an increased detection rate of cervical precancerous lesions with liquid-based cytology, but the number of false positive tests is still high. The specificity of the two tests seems similar, but this cannot be ascertained exactly, because of the fact that follow-up of negative cases is unavailable.     

Rapid detection of HSV from cytologic specimens collected into ThinPrep fixative

OBJECTIVE: Herpes simplex virus (HSV) infection is associated with substantial morbidity and mortality in neonates. A diagnosis of HSV on cervical cytologic studies could lead to a cesarean section, with an increase in the risk of maternal morbidity. The identification of viral lesions in sexually active women has medical and social implications. There have been reports of false positive diagnoses of HSV in patients with altered endocervical cells and with cervical intraepithelial neoplasia 3. We evaluated a polymerase chain reaction (PCR)-based assay to detect HSV-1 and HSV-2 in routinely collected cervical cytology specimens in ThinPrep fixative (Cytyc Corp., Marlborough, Massachussets, U.S.A.). STUDY DESIGN: DNA was extracted from five cases that demonstrated cytologic changes suggestive of an HSV infection. PCR amplification with subsequent gel electrophoresis was performed to detect the presence of HSV. RESULTS: HSV DNA was detected in three of five cases that were cytologically diagnosed as suspicious or strongly suspicious for HSV infection. CONCLUSION: The combination of the ThinPrep liquid-based method for cervical cytology with PCR allows prompt confirmation of the diagnosis of HSV without sacrificing the diagnostic morphology on the slide.     

Cellular Differences Between True Negative and False Negative Papanicolaou Smears

A matched case-control study of 123 false negative Papanicolaou smears and 488 true negative Papanicolaou smears was undertaken to determine the association between the types of cells present on the smear and the correctness of the cytology report. the false negative slides were significantly more likely to include endocervical columnar cells than the true negative slides (odds ratio 1.90, 95% confidence interval (CI) 1.21–3.01). No statistically significant difference in metaplastic cell status was evident (odds ratio 1.48, 95% CI 0.95–2.30). When considered together, metaplastic and/or columnar cells were significantly more likely to be present in false negative smears than in true negative smears (odds ratio 1.87, 95% CI 1.13–3.08). the implications of these findings for improving the accuracy of cervical cytology for the detection of precancerous lesions are discussed.     

宫颈癌患者液基细胞学与组织学诊断的比较分析 仇

目的:通过对液基细胞学检测(TCT)与组织学活检的比较分析,探讨TCT出现漏诊的原因。方法:收集83例宫颈癌患者的宫颈活检组织蜡块和宫颈脱落细胞标本,组织蜡块行常规病理切片检查,脱落细胞标本进行TCT检测。结果:和组织病理学诊断结果比较,这些患者的TCT诊断漏诊18例。进行过抗HPV治疗的宫颈癌患者,其TCT漏诊率明显高于未治疗者(P<0.05)。结论:TCT在宫颈癌筛查中存在一定的漏诊,其产生的原因与癌细胞分化程度、宫颈糜烂程度、非诊断细胞的干扰、不当的采集方法及抗HPV治疗有关。     

Large performance variation does not affect outcome in the Finnish cervical cancer screening programme

S. Lönnberg, P. Nieminen, L. Kotaniemi‐Talonen, H. Kujari, J. Melkko, G. Granroth, M. Vornanen, T. Pietiläinen, J. Arola, J. Tarkkanen, T. Luostarinen and A. Anttila Large performance variation does not affect outcome in the Finnish cervical cancer screening programme Objective: Cytology screening for prevention of cervical cancer can reduce incidence and mortality by more than 80% in settings with good organization and rigorous quality control. Audit studies are essential for reaching and maintaining a high quality of screening. The aim of this study was to evaluate variation in performance indicators by screening laboratory and assess the impact on the effectiveness of screening as indicated by cervical intraepithelial neoplasia grade 3 and above (CIN3+) rates after a negative screen. Methods: Seven cytology screening laboratories operating during 1990–1999 with a total of 953 610 screening tests performed were included in the study. By linking screening and cancer register files, all cases of CIN3+ diagnosed in the screened population were identified. For 395 CIN3+ cases with a preceding negative screen and 787 controls, a re‐evaluation of smears was undertaken to uncover false negative screening tests. Performance parameters and rates of CIN3+ after a negative screen were analysed for interlaboratory heterogeneity. Results: The rates of follow‐up recommendations and referrals varied by up to 3.6‐ (2.8–10.2%) and 4.0‐fold (0.03–0.12%), respectively. CIN1, CIN2 and CIN3+ screen detection rates differed by up to 8.5‐ (0.02–0.17%), 5.4‐ (0.05–0.25%) and 3.3‐fold (0.05–0.18%). False negative rates determined by re‐evaluation showed up to 2.1‐fold differences (29–62%). Rates of CIN3+ after a negative screen (0.023–0.048%) and as a proportion of total CIN3+ (15–31%) in the screened population were low and did not vary significantly. Conclusions: There were large variations in the sensitivity–specificity trade‐off between laboratories, reflected in all performance indicators as well as in the test validity estimates of the re‐evaluation phase, but not in screening effectiveness. Even though performance variations do not always have an impact on the effectiveness of screening, they lead to variations in cost, treatment and psychological burden, and should be addressed.