Combination Of Cytology Research Articles

Value of endocervical margin and high-risk human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia, adenocarcinoma in situ, and microinvasive carcinoma of the uterine cervix

ObjectiveThe aim of this study was to analyze clinico-pathologic factors and the optimal cut-off value of high-risk human papillomavirus (HR-HPV) viral load for predicting high-grade residual/recurrent disease after the conization in cervical intraepithelial neoplasia (CIN 2–3), adenocarcinoma in situ (AIS), and microinvasive carcinoma of the uterine cervix (MICA). MethodsWe retrospectively reviewed data from 701 patients with CIN 2–3, AIS, and MICA who underwent conization between September 2003 and June 2012. Receiver-operating characteristic curve analysis was used to find out the cut-off value of HR-HPV viral load for predicting residual/recurrent disease. Clinico-pathologic variables, including resection margin and HR-HPV status, were evaluated as possible predictors of residual/recurrent disease. ResultsAt a cut-off value of 1.16 RLU/CO for post-cone HR-HPV viral load, the sensitivity was 88.2% and the specificity was 98.3%. Multivariate analysis demonstrated that post-cone cytology (p=0.001, OR=83.808, 95% CI=6.688–1050.232), endocervical margin status (p<0.001, OR=80.478, 95% CI=7.421–872.732), and post-cone HR-HPV status (p<0.001, OR=79.660, 95% CI=8.539–743.129) were significantly associated with residual/recurrent disease. The post-cone HR-HPV positivity was observed more in the patients who showed positive endocervical margin than in the patients with positive ectocervical margin (32.6% vs. 5.3%, p=0.002). ConclusionsFollow-up using liquid based cytology in combination with HR-HPV test at 12months after the conization, and not the early HR-HPV test, might be acceptable. Post-cone endocervical margin status combined with post-cone HR-HPV test is critical for predicting residual/recurrent disease and clinical management.

Does imprint cytology improve the accuracy of transrectal prostate needle biopsy?

To evaluate the accuracy of imprint cytology of core needle biopsy specimens in the diagnosis of prostate cancer. Between December 24, 2011 and May 9, 2013, patients with an abnormal DRE and/or serum PSA level of >2.5 ng/mL underwent transrectal prostate needle biopsy. Samples with positive imprint cytology but negative initial histologic exam underwent repeat sectioning and histological examination. 1,262 transrectal prostate needle biopsy specimens were evaluated from 100 patients. Malignant imprint cytology was found in 236 specimens (18.7%), 197 (15.6%) of which were confirmed by histologic examination, giving an initial 3.1% (n = 39) rate of discrepant results by imprint cytology. Upon repeat sectioning and histologic examination of these 39 biopsy samples, 14 (1.1% of the original specimens) were then diagnosed as malignant, 3 (0.2%) as atypical small acinar proliferation (ASAP), and 5 (0.4%) as high-grade prostatic intraepithelial neoplasia (HGPIN). Overall, 964 (76.4%) specimens were negative for malignancy by imprint cytology. Seven (0.6%) specimens were benign by cytology but malignant cells were found on histological evaluation. On imprint cytology examination, nonmalignant but abnormal findings were seen in 62 specimens (4.9%). These were all due to benign processes. After reexamination, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, false-positive rate, false-negative rate of imprint preparations were 98.1, 96.9, 98.4, 92.8, 99.3, 1.6, 3.1%, respectively. Imprint cytology is valuable tool for evaluating TRUS-guided core needle biopsy specimens from the prostate. Use of imprint cytology in combination with histopathology increases diagnostic accuracy when compared with histopathologic assessment alone.

Discovery of Apo-A1 as a potential bladder cancer biomarker by urine proteomics and analysis

Bladder cancer is clinically characterized by high recurrent rate and poor prognosis and thereby patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method for detecting and monitoring bladder cancer would thus be advantageous. In this study, by using the two-dimensional electrophoresis (2-DE) approach with subsequent mass spectrometry (MS), we demonstrated the increased expression of apolipoprotein-A1 (Apo-A1) in individual urine from patients with bladder cancer, which was confirmed by Western blot results. A further analysis of the urinary Apo-A1 levels by an enzyme-linked immunosorbent assay yielded results that were consistent with the Western blot, and suggested Apo-A1 could provide diagnostic utility to distinguish patients with bladder cancer from healthy controls at 19.21ng/ml. Further validation assay in a larger number of urine samples (n=379) showed that Apo-A1 could be used as a biomarker to diagnosis bladder cancer with a sensitivity and specificity of 89.2% and 84.6% respectively. Moreover, the application of exfoliative urinary cytology in combination with the urine Apo-A1 detection could significantly increased the sensitivity in detecting bladder cancer. Our data showed a significant relationship of expressed Apo-A1 was established between bladder cancer and normal controls. Apo-A1 could be a potential biomarker for the diagnosis of bladder cancer.

Combined 99mTc-methoxyisobutylisonitrile scintigraphy and fine-needle aspiration cytology offers an accurate and potentially cost-effective investigative strategy for the assessment of solitary or dominant thyroid nodules: reply to comments by Riazi et al.

Combined 99mTc-methoxyisobutylisonitrile scintigraphy and fine-needle aspiration cytology offers an accurate and potentially cost-effective investigative strategy for the assessment of solitary or dominant thyroid nodules: reply to comments by Riazi et al.

A Clinicopathologic Study of Vaginal Intraepithelial Neoplasia

To evaluate the natural history of vaginal intraepithelial neoplasia (VAIN) and to identify risk factors for invasive vaginal carcinoma. The records of all women with VAIN diagnosed at military treatment facilities over a 10-year period with minimum follow-up of 12 months were reviewed. Patient demographics and clinical information related to the diagnosis and treatment of VAIN were recorded. One hundred twenty-seven women with VAIN met inclusion criteria. The mean age was 47.4 years, and median surveillance was 34 months (range 12-169 months). Seventy-five patients had low-grade vaginal dysplasia as their initial diagnosis, and 15 (20%) of these patients underwent treatment. Fifty-two patients had high-grade vaginal dysplasia, of which 38 (73%) underwent treatment. Overall, 113 patients (89%) demonstrated normalization of disease, 11 patients (9%) demonstrated persistence of disease, and three patients (2%) experienced recurrence of disease. No patients experienced development of invasive vaginal carcinoma. However, median time to normalization was 6 months longer in patients with low-grade dysplasia compared with those with high-grade dysplasia (15.9 months compared with 10.0 months; hazard ratio 1.5; 95% confidence interval 1.004-2.1; P=.045). Patients with high-grade dysplasia had more biopsies performed during their surveillance than patients with low-grade dysplasia (3.3 compared with 2.5; P=.045). Overall, 89% of patients demonstrated normalization of VAIN, and none had progression to invasive cancer. Normalization, persistence, and recurrence rates did not significantly differ by grade of dysplasia or treatment status. Based on our findings regarding the time to normalization, annual surveillance with combined cytology and colposcopy is likely adequate. Because 11% of patients with VAIN either will experience recurrence or will have persistent disease, lifetime surveillance is recommended. : III.

Utility of Flow Cytometry of Cerebrospinal Fluid as a Screening Tool in the Diagnosis of Central Nervous System Lymphoma

Experiences at our institution show that flow cytometry analysis (FCA) has become routine clinical practice in the workup of patients with altered mental status, even if risk factors are low. To assess diagnostic accuracy of combined FCA and cytology in the diagnosis of central nervous system lymphoma in an unselected patient population with neurologic symptoms, including patients with no history of lymphoma or suspicious radiology. Between 2001 and 2011, cerebrospinal fluid was submitted from 373 patients for lymphoma screening by FCA. The medical records were reviewed for patient symptomatology, history of malignancy, brain imaging, FCA results, cytology results, brain biopsy, and clinical follow-up. A lymphoid malignancy was detected by FCA in 4% of cases. A positive diagnosis was more likely in patients with either a history of hematologic malignancy and/or a suspicious radiology result (P = .009). All patients with no history of lymphoma and no suspicious radiology (n = 102) had negative cytology, and none had a correspondingly positive FCA result. The positive and negative predictive values of combined cytology and FCA in the patients with history of lymphoma and/or abnormal imaging results were 92% and 89%, respectively, when compared with open brain tissue biopsy, and 89% and 86%, respectively, when compared with clinical follow-up. When low-risk patients were included, the positive predictive value remained at 92%, but the negative predictive value dropped to 52% with the open brain biopsy as the reference, and values did not change significantly for the group with clinical follow-up. Concurrent FCA and cytology are most useful in the appropriate clinical setting, and we propose a triage algorithm for how FCA on cerebrospinal fluid is best used.

Diagnostic Testing of Primary Vitreo-Retinal Lymphoma

Primary Vitreo-Retinal Lymphoma (PVRL) or Primary Intra-Ocular Lymphoma (PIOL) is a rare malignancy often seen as a context of primary central nervous system lymphoma (PCNSL). This article reviews the diagnostic approach of PVRL. The techniques for diagnosing PVRL from ocular biopsy specimens includes cytologic analysis, immuno-cytochemistry, flow-cytometry, polymerase chain reaction (PCR) to detect V-J Ig gene re-arrangements, and analysis of IL6, IL10 in aqueous or vitreous fluid. Currently, cytology in combination with immunohistochemistry is considered the gold standard for the diagnosis of PVRL. But ancillary tests including IgH, TCR gene rearrangements and cytokine analysis are reliable biomarkers for B and T cell PVRL. Genetic testing with t(14:18) detection may show promising results in future.

Analyzing S100A6 Expression in Endoscopic Ultrasonography-guided Fine-needle Aspiration Specimens

Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) cytology in combination with other tests is necessary to improve diagnostic accuracy. We evaluated the diagnostic utility of S100A6 expression in EUS-FNA tissue samples in pancreatic ductal adenocarcinoma (PDA). RNA was extracted from 36 PDA and 44 nontumor pancreatic tissues obtained during surgery. S100A6 expression was quantified by real-time reverse transcription-polymerase chain reaction, and receiver operating characteristic analysis was performed to determine the cutoff value for PDA. We preoperatively performed EUS-FNA in 52 patients with pancreatic masses, then prospectively evaluated the diagnostic value of S100A6 expression of EUS-FNA samples in pancreatic cancer diagnosis. S100A6 immunohistology was conducted to validate the S100A6 expression data in PDA samples. Of the 52 EUS-FNA patients with pancreatic masses, RNA was successfully extracted from 44, which comprised 34 pancreatic cancer patients and 10 patients with benign pancreatic diseases. Cytology results were malignant in 23 cases, benign in 9, and atypical or abnormal in 12. The sensitivity, specificity, and accuracy of cytology for diagnosis of pancreatic cancer were 67.65%, 100%, and 75%, respectively. When an S100A6 expression >0.005248 was defined as positive for malignancy, the sensitivity, specificity, and accuracy of S100A6 expression of EUS-FNA for diagnosis of pancreatic cancer were 88.24%, 90.00%, and 88.64%, respectively. Quantification of S100A6 expression in EUS-FNA samples had a high sensitivity and specificity for the diagnosis of PDA.

Cytohistological correlation in diagnosis of lung tumors by using fiberoptic bronchoscopy: Study of 200 cases

Examination of specimens obtained through flexible fiberoptic bronchoscope is an important and often the initial diagnostic technique performed in patients with suspected malignant lung lesion. To evaluate the correlation of cytological findings of bronchial washings, bronchial brushing and imprint smear of bronchial biopsy in the diagnosis of lung tumors, with histopathology of bronchial biopsy taking the latter as the confirmatory diagnostic test. A total of 200 patients with lung mass were included in the study. Bronchial brushings were obtained from all 200 cases. In the first 100 cases, pre-biopsy bronchial washing (washing collected before the brushing and biopsy procedure) while post-biopsy washing (washing at the end of the procedure) was procured in all 200 cases. Imprint smears of bronchial biopsy were prepared in 150 cases. Sensitivity and specificity of brushing was 76.58% and 77.78% respectively and that of imprint smear was 81.35% and 78.12% respectively. Pre-biopsy and post-biopsy washing showed high specificity of 88.89%, but low sensitivity of 30.14 and 36.77% respectively. No significant difference was found in sensitivity between brushing and imprint smear (Chi-square; P = 0.4187); and between pre-biopsy and post-biopsy washing (Chi-square; P = 0.7982). However, there was a significant difference between sensitivity of brushing and washing (Chi-square; P = 0.0001). The sensitivity of combination of three cytological diagnostic techniques was 87.29%. Bronchial brushing and washing cytology in combination with imprint cytology aids in the diagnosis of lung tumors. Therefore, all these techniques may be used concurrently along with bronchial biopsy to diagnose lung tumors.

HPV Co-testing in Patients over 30: Significance of a Positive HPV Result in the Cytology Negative Diagnosis

Introduction: Combined cytology and high-risk human papillomavirus (HR-HPV) screening for women over the age of 30 (HPV 30) became available at our institution in September of 2007. The goal of this study was to investigate patient follow up on cytology negative HR-HPV positive cases over a four year time period in women over the age of 30. Materials and Methods: HR-HPV screening using Hybrid Capture/Digene and routine cytology were performed as part of clinical practice for women over the age of 30 between September 2007 and September 2011. Patients with a negative cytology result and a positive HR-HPV test were retrospectively identified. Tissue and cytology follow-up data were collected. Results: A computer based search identified 32,803 HPV 30 tests that were ordered between September 2007 and September 2011. Of the 30,671 cases that were negative by cytology, 979 had positive HR-HPV results. Of these 979 cases with a negative cytology/positive HR-HPV diagnosis, 476 patients had tissue or cytology follow up. These cases comprise our study population.

Human Papillomavirus genotype testing combined with cytology as a ‘test of cure’ post treatment: The importance of a persistent viral infection

Background Human Papillomavirus (HPV) testing has been evaluated as a test of cure in patients following treatment of high-grade cervical intraepithelial neoplasia (CIN2+). Studies show that women who are HPV and cytology negative post treatment can be safely returned to routine recall. The management strategy for HPV positive women requires confirmation. Objective To evaluate the clinical utility of the PapilloCheck ® genotyping assay for predicting disease recurrence in a test of cure setting. Study design Ninety-eight women (19–52 years) treated for CIN2+ by large loop excision of the transformation zone (LLETZ) were evaluated with samples taken before and 6 months after treatment for HPV testing. Cytology and histology were available from recruitment until 24 months post treatment. Results Recurrent disease was evident in 4% of patients with 2 cases low-grade and 2 cases of high-grade disease. In women with no disease recurrence, 40% (95% CI 30.42–51.05%) were high risk (HR) HPV negative post LLETZ. Both cases with high-grade disease had persistent HPV16 infection. Genotyping before and after treatment revealed 83% (95% CI 75.74–88.78%) of total viral infections were cleared and 17% (95% CI 11.22–24.26) viral infections persisted. Post treatment, combined cytology and HPV test results predicted CIN2+ with 100% sensitivity, 91.7% specificity, 100% NPV and 20% PPV and measuring viral persistence marginally increased specificity and PPV. Conclusion Post treatment, cytology combined with a single HR HPV test has high sensitivity and specificity for predicting disease recurrence. HPV genotyping before and after LLETZ identifies persistent viral infections and could help refine patient management.

Comparison of 21-gauge and 22-gauge Needles for Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration of Mediastinal and Hilar Lymph Nodes

: Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) using a 22-gauge needle has emerged as an accurate, minimally invasive, and safe technique for accessing undiagnosed mediastinal adenopathy, particularly in patients with lung cancer, the small sample size obtained by a conventional needle may limit the accuracy of the result. : We evaluated the safety and efficacy of obtaining specimens using 21-gauge needles, comparing diagnostic yield with conventional 22-gauge needles. : Participants consisted of 56 consecutive patients with mediastinal lesions referred to our institution for diagnostic EBUS-TBNA. The 21-gauge needle group (21 G) included 24 patients with 6 nonmalignancies and the 22-gauge needle group (22 G) included 32 patients with 9 nonmalignancies. Final diagnosis was based on cytology, histology, surgical results, appropriate clinical pictures on examination, and/or clinical follow-up. : Comparing 21 G and 22 G, inadequate material rates were 0% versus 3.1% in cytology, and 4.2% versus 18.8% in histology, respectively. Accuracy in cytology, histology, and combined cytology and/or histology were 91.7% versus 65.6% (P=0.02), 95.8% versus 81.3% (P=0.11), and 100% versus 84.4% (P=0.04), respectively. After limiting cases to suspected malignancies, sensitivity in cytology, histology, and combined cytology and/or histology were 88.9% versus 52.2% (P=0.01), 100% versus 82.6% (P=0.09), and 100% versus 87.0% (P=0.17), respectively. : Increasing sample volume using a 21-gauge needle rather than a 22-gauge needle might improve diagnostic yield in EBUS-TBNA. This study revealed the benefits of using a 21-gauge needle for cytological and histologic diagnostic yields.

Evaluation of 14 triage strategies for HPV DNA‐positive women in population‐based cervical screening

High-risk human papillomavirus (hrHPV) testing has a higher sensitivity but lower specificity than cytology for detection of high-grade intraepithelial neoplasia (CIN). To avoid over-referral to colposcopy and overtreatment, hrHPV-positive women require triage testing and/or followup. A total of 25,658 women (30-60 years) enrolled in a population-based cohort study had an adequate baseline Pap smear and hrHPV test. The end-point was cumulative two-year risk of CIN grade 3 or worse (CIN3+). In a post-hoc analysis, fourteen triage/followup strategies for hrHPV-positive women (n = 1,303) were evaluated for colposcopy referral rate, positive (PPV) and negative predictive value (NPV). Five strategies involved triage testing without a repeat test and nine strategies involved triage testing followed by one repeat testing. The tests were cytology, hrHPV, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping. Results were adjusted for women in the cohort study who did not attend repeat testing. Of the strategies without repeat testing, combined cytology and HPV16/18/31/33/45 genotyping gave the highest NPV of 98.9% (95%CI 97.6-99.5%). The corresponding colposcopy referral rate was 58.1% (95%CI 55.4-60.8%). Eight of the nine strategies with retesting had an estimated NPV of at least 98%. Of those, cytology triage followed by cytology at 12 months had a markedly lower colposcopy referral rate of 33.4% (95%CI 30.2-36.7%) than the other strategies. The NPV of the latter strategy was 99.3% (95%CI 98.1-99.8%). Triage hrHPV-positive women with cytology, followed by repeat cytology testing yielded a high NPV and modest colposcopy referral rate and appear to be the most feasible management strategy.

Role of DNA flow cytometry and immunocytochemical analysis in diagnosis of malignant effusions

Body cavity fluid examination sometimes presents a diagnostic challenge in cytology practice. This study was undertaken to evaluate efficacy of cytomorphology, epithelial membrane antigen immunocytochemistry (EMA-ICC) and DNA flow cytometry (FCM) in detection of malignant cells in effusions. One hundred effusions (55 pleural, 44 ascitic, and 1 pericardial fluid) were studied by cytology, EMA, and FCM. There were 29 malignant and 71 benign cases. On cytology, 28 of 29 malignant cases were diagnosed. With no false positives, the sensitivity and specificity was 96.55% and 100% respectively. FCM detected aneuploidy in 85.71% of cytologically malignant and 4.17% of cytologically benign effusions. EMA was positive in 75% of cytologically malignant and 4.17% of cytologically benign cases. EMA had lower sensitivity than cytology; 75.86% versus 96.55%. Sensitivity and specificity of FCM was 86.21%, and 97.18% respectively. FCM had lower sensitivity than cytology; 86.21% versus 96.55%. Sensitivity increased to 100% (P < 0.05) when the combinations of cytology plus EMA or cytology plus ploidy were applied compared to cytology alone (96.55%). Also, the combination of cytology plus EMA had higher sensitivity than EMA alone (100% versus 75.86%, P < 0.05) and combined cytology plus ploidy had higher sensitivity than ploidy alone (100% versus 86.21%, P < 0.05). The study demonstrates the usefulness of EMA-ICC and DNA FCM as adjuncts to cytology to diagnose malignancy in effusions. FCM in combination with ICC can be further developed to reduce number of false-negative cases on cytology and add objectivity to cytologically doubtful or equivocal cases.

366 FLUORESCENCE IN SITU HYBRIDIZATION ASSAY AS AN ADJUNCTIVE TEST FOR THE DIAGNOSIS OF URINARY TRACT CARCINOMA IN CASE OF EQUIVOCAL CYTOLOGY

You have accessJournal of UrologyUrothelial Cancer: Markers + Natural History & Pathophysiology1 Apr 2011366 FLUORESCENCE IN SITU HYBRIDIZATION ASSAY AS AN ADJUNCTIVE TEST FOR THE DIAGNOSIS OF URINARY TRACT CARCINOMA IN CASE OF EQUIVOCAL CYTOLOGY Pieter Visser, Esther T. Kok, Bob T. Merks, and J.L.H. Ruud Bosch Pieter VisserPieter Visser Utrecht, Netherlands More articles by this author , Esther T. KokEsther T. Kok Utrecht, Netherlands More articles by this author , Bob T. MerksBob T. Merks Utrecht, Netherlands More articles by this author , and J.L.H. Ruud BoschJ.L.H. Ruud Bosch Utrecht, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.452AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urinary cytology in combination with cystoscopy is commonly used for the diagnosis of urinary tract carcinoma. Unfortunately, cytology has a poor sensitivity for low grade tumors and frequently reports atypical findings. This can cause a dilemma for the clinician and may be a reason for further investigation. Therefore the Fluorescence in situ hybridization (FISH; UroVysion®) assay might be helpful. The aim of this study is to investigate the value of FISH in the primary detection of urothelial cell carcinoma in general and more specifically when urinary cytology is equivocal. METHODS Medical records were retrospectively reviewed for 160 patients, who were screened for primary urothelial cell carcinoma between September 2007 and October 2009. Patients in whom both cytology and FISH assay was performed were included in the study. All urine samples were interpreted by an experienced cytopathologist. The differences in sensitivity and specificity between cytology and FISH were calculated using a McNemar test. Clinical stage of carcinoma was classified according to the TNM staging system and the tumor grade was assigned according to the WHO guidelines. Carcinoma was diagnosed by cystoscopy and histologically confirmed. RESULTS In total 160 patients were included. After exclusion of uninformative FISH assays, 138 patients remained (71% men vs 29% women) with a mean age of 65 years. In 44 patients (31.4%) urothelial cell carcinoma was diagnosed. The sensitivity and specificity of FISH and cytology was 73% and 45% (p = 0.021), and 83% and 96% (p = 0.008), respectively. The positive and negative predictive value of FISH and cytology was 67% and 86%, and 87% and 82%, respectively. In 84 of the 160 patients, cytology was equivocal, although urothelial cell carcinoma was later diagnosed in 22 of these cases. In these 22 patients, the related FISH detected a Ta tumor in 4 cases, a T1 tumor in 2 cases, a T2 tumor in 2 cases and CIS in one case. The related FISH was negative in 9 (41%; Ta; 5 times; T1; one time; T2; 2 times) and uninformative in 4 cases (18%). CONCLUSIONS Although the specificity of FISH compared to cytology is lower, it has a significantly higher sensitivity. Therefore, a FISH assay is beneficial as an adjunctive test for the detection of urothelial cell carcinoma, particularly when cytology is equivocal. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e149 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pieter Visser Utrecht, Netherlands More articles by this author Esther T. Kok Utrecht, Netherlands More articles by this author Bob T. Merks Utrecht, Netherlands More articles by this author J.L.H. Ruud Bosch Utrecht, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Atypical Squamous Cells, Cannot Exclude High-Grade Squamous Intraepithelial Lesion

To review the cytology category atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), with human papillomavirus (HPV) and other ancillary testing results and according to age group. A literature search was performed on the ASC-H category, and studies analyzing ASC-H according to ancillary testing modalities or patient age groups during the past 4 years were emphasized. The ASC-H category accounts for less than 1% of cytology reports, and 33% to 84% will test positive for oncogenic HPV. The number of patients with cervical intraepithelial neoplasia 2/3 and cancer on biopsy is quite variable, from about 12% to more than 70%, averaging about 40%. The variation reflects patient population as well as local laboratory practices, but older subgroups are more likely to have negative HPV results and negative follow-up. Both the sensitivity of HPV testing for cervical intraepithelial neoplasia 2/3 detection and the negative predictive value for a patient with ASC-H and negative HPV testing average more than 95%. Additional studies evaluating other types of ancillary testing for the ASC-H category are needed. Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, is an uncommon cytology result, and HPV testing results and biopsy follow-up show variation according to patient age group and local laboratory practices. A negative HPV result in ASC-H offers a high negative predictive value and could be considered as a management strategy in mature women as well as women 30 years and older receiving combined cytology and HPV screening.

High-Risk HPV Testing in Women 30 Years or Older With Negative Papanicolaou Tests

Cervical screening with combined cytology and high-risk human papillomavirus (HR-HPV) detection has been approved for women 30 years or older. We investigated the clinical use of cotesting for women with negative Papanicolaou tests. Follow-up cytology, HR-HPV test, and biopsy findings were identified during an 18-month period. In 1 year, 2,719 cotests from 2,686 women were identified; 146 were positive for HR-HPV. Among women with positive HR-HPV testing, 120 had follow-up, including 70 with repeated cotesting, and 3 had high-grade dysplasia identified (2.5% of women with follow-up). In 1,334 women with initial double-negative cotest results who had repeated cytologic testing within 18 months, 2 high-grade dysplasias were found (0.1%). The vast majority of cotest results are double-negative. Among tests that show HR-HPV positivity, the prevalence of underlying high-grade dysplasia is low. About half of all women who undergo cotesting receive follow-up that is not in accord with published guidelines.

S1470: Improved Detection of Malignant Biliary Strictures With Addition of K-ras Gene Mutation Analysis to Brushing Cytology and Biopsies

Accurate pre operative diagnosis of malignant biliary strictures is important for treatment and prognosis. Endoscopic retrograde cholangio pancreaticography (ERCP) in addition to evaluating the location and morphology of biliary strictures allows for tissue sampling. In this study the diagnostic yield of biliary brushing cytology and biopsies in combination with K-ras gene mutation was evaluated.

Improved Detection of Cervical Cancer and High Grade Neoplastic Lesions by a Combination of Conventional Cytology and DNA Automated Image Cytometer

OBJECTIVE: To reduce false-negative rates of population based cervical screening programs employing conventional cytology in combination with automated DNA image cytometer. METHODS: Involved cervical samples from a total of 3603 women were taken by a cervix brush and then placed into a fixative solution. The cells were separated from mucus by mechanical and chemical treatment after which they were deposited onto microscope slides by a cytospin. Two slides were prepared from each case; one slide was stained by Papanicolaou stain for conventional cytology examination, while the other slide was stained by a DNA specific and stoichiometric stain. The latter slide was used to determine the relative amount of DNA in the cell nuclei in order to assess the ploidy status of the epithelial cells. Enrolled in the study, 157 women were followed by colposcopy examination where punch biopsies were taken from the visible lesions or from suspicious areas. The results of the conventional cytology were then compared to the DNA image cytometer for all samples. RESULTS: Histopathology diagnosed 51 lesions from the 132 biopsied cases as CIN2 or higher, including 27 CIN2, 16 CIN3 and 8 invasive cancers. Conventional cytology correctly identified 29 of the 51 high grade CIN and in-vasive cancer, while DNA image cytometer correctly identified 38 high grade CIN and invasive cancer using the crite-rion that at least three cells were found on the slide that contained DNA amount in excess of 5c. 42 out of 51 high grade CIN and invasive cancer were found by conventional cytology in combination with DNA image cytometer. Sensitivities were 56.8%, 74.5% and 82.4%, while specificities were 86.2%, 81.5% and 81.5% in conventional cytology, DNA image cytometer and combination both cytology and DNA image cytometer respectively. CONCLUSION: The study demon-strated that screening for high grade neoplastic lesions and cervical cancer by DNA image cytometer or combination of conventional cytology and DNA image cytometer is more sensitive than conventional screening approach.

Comparison of the Clinical Performance of PapilloCheck Human Papillomavirus Detection with That of the GP5+/6+-PCR-Enzyme Immunoassay in Population-Based Cervical Screening

We compared the clinical performance of the PapilloCheck human papillomavirus (HPV) assay with that of the GP5+/6+-PCR method with an enzyme immunoassay readout (GP5+/6+-PCR-EIA) for the detection of high-risk HPV (hrHPV) types by the use of cervical samples originating from women in a population-based by the use of cervical screening cohort tested by combined cytology and GP5+/6+-PCR-EIA (POBASCAM trial). Specimens from a random sample of 1,437 controls (women ages 40 to 60 years with normal cytological findings and without evidence of cervical intraepithelial neoplasia grade 2 or higher [> or = CIN2] within up to 8 years of follow-up) and 192 cases (women ages 30 to 60 years in whom > or = CIN3 was detected within up to 3 years of follow-up) were subjected to analysis by the PapilloCheck method. When all 17 (probably) hrHPV types were taken into account, the PapilloCheck assay had a clinical sensitivity for the detection of > or = CIN3 of 96.4% (185/192 samples; 95% confidence interval [CI], 93.7 to 99.7) and a clinical specificity for the detection of > or = CIN2 of 96.3% (95% CI, 95.3 to 97.3). After restriction of the analysis by the PapilloCheck assay to the 14 hr HPV types targeted by GP5+/6+-PCR-EIA, the clinical sensitivity and clinical specificity values were 95.8% (95% CI, 92.8 to 98.8) and 96.7% (95% CI, 95.7 to 97.7), respectively. By comparison, these values were 96.4% (95% CI, 93.9 to 98.9) and 97.7% (95% CI, 96.9 to 98.5), respectively, for the GP5+/6+-PCR-EIA. When all 17 (probably) hrHPV types were included in the analysis, noninferiority score testing revealed that the clinical sensitivity of the PapilloCheck assay for the detection of > or = CIN3 was noninferior to that of the GP5+/6+-PCR-EIA (P < 0.0001), but the clinical specificity of the PapilloCheck assay for the detection of > or = CIN2 was inferior to that of the GP5+/6+-PCR-EIA (P = 0.08) when lower bounds of 90% for sensitivity and 98% for specificity were used. When the analysis was restricted to the 14 hrHPV types targeted by the GP5+/6+-PCR-EIA, both the clinical sensitivity and the clinical specificity of the PapilloCheck assay were noninferior to those of the GP5+/6+-PCR-EIA (noninferiority score test; P < 0.0001 and P = 0.007, respectively). Thus, when the findings obtained for the 14 hrHPV types detectable by the GP5+/6+-PCR-EIA are considered, the PapilloCheck assay is clinically compatible with the GP5+/6+-PCR-EIA.