Detection of high grade squamous intraepithelial lesions and tumors using the AutoPap System: results of a primary screening clinical trial.

BACKGROUND: The AutoPap System for the initial screening and quality control of conventional cervical cytology slides previously has shown superior performance for the detection of abnormal slides of low grade squamous intraepithelial lesions and above. This report presents data regarding the important category of high grade squamous intraepithelial lesions and above (HSIL+). METHODS: All slides were run through a Current Practice (CP) arm of manual screening with 10% random quality control followed by an AutoPap (AP) arm of device initial screening with approximately 25% of slides receiving no further review; 75% received a manual rescreen with AP ranking and QC rescreening of 15% of the top ranking negative manual screen slides was performed. Detection performance for truth-determined HSIL+ cases was compared between the two study arms. Available follow-up biopsy results were correlated for cases determined to be HSIL+. RESULTS: Of 25,124 analyzed slides, 70 slides had truth-determination at the HSIL+ level (67 HSILs, 1 adenocarcinoma in situ, and 2 invasive tumors). The AP arm identified 68 of 70 cases (including both invasive tumors). Neither false-negative HSIL+ was found in the 25% "No Further Review" population. The CP arm identified 65 of 70 cases (missing both invasive tumors). The results showed statistical equivalence between the two arms (P = 0.0129). Biopsy follow-up was available in 27 of 70 HSIL+ cases identified by AP and showed abnormality at some level in 100% of cases. CONCLUSIONS: The AP arm was statistically equivalent and showed numeric superiority to the CP arm for the category of HSIL+. Follow-up data confirmed the true-positive nature of these findings. These results are significant because any overall improvement in the performance of an initial screening device must be paralleled by at least equivalence in the clinically important subset category of HSIL+. Cancer (Cancer Cytopathol)

AutoPap system detection of infections and benign cellular changes: results from primary screener clinical trials.

Primary screening devices for cervical cytology must show performance data for the detection of infectious organisms and benign cellular changes (BCC) for cytologists who routinely report these findings. The data on infection and BCC from the AutoPap primary screening clinical trials are presented herein. The presence of infectious organisms (candida, trichomonas, shift in bacterial flora, herpes, actinomyces) and BCC were noted in each of the clinical trial arms (current practice, CP; AutoPap-assisted practice, AP). For the purposes of these analyses, a report of infection or BCC from either arm was considered to be "truth." In 25,124 slides analyzed, there were 2,925 cases of infection identified. Of these, CP identified 2,141, and AP identified 1,985. The overall detection results are statistically equivalent. Of 17 cases of actinomyces, CP detected 8, while AP detected 12. Of 1,282 cases of candida, CP detected 983, and AP detected 865. Of 1,375 cases of shift of bacterial flora, CP detected 897, and AP detected 869. Of 14 cases of herpes, CP detected 9, and AP detected 11. Of 343 cases of trichomonas, CP detected 293, and AP detected 275. There were 5,156 cases of BCC identified in the trial. CP detected 3,431, and AP detected 3,276. The detection rates for BCC are statistically equivalent. The results show that the AutoPap-assisted practice for the primary screening of conventional cervical cytology slides is equivalent to the current practice for the detection of cervical infections and benign cellular changes.

Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results.

CONTEXT: A Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results. OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing. DESIGN AND SETTING: Natural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996. PARTICIPANTS: From a cohort of 46009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified. MAIN OUTCOME MEASURES: Cervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology. RESULTS: Of 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1 % (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%). CONCLUSIONS: For women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.

A task-targeted automation system: a case study.

Kaiser Permanente's Northern California Regional Laboratory recently achieved an important milestone in its continuous quality improvement project by automating time-consuming and labor-intensive tasks involved in preanalytical and postanalytical sample processing. The new task-targeted automation system, the most sophisticated of its kind in the world, consists of three key components: the Roche Diagnostics PSD 1 primary sample decapper/sorter/archiver, the Roche Diagnostics VS 250 aliquoter, and a data manager/process controller developed by Data Innovations. The system was placed into service in April 1998, culminating more than a year of planning and implementation. Within months after the system went into operation, the laboratory observed significant improvements in workflow and efficiency, as well as a reduction in work-related injuries. The purpose of this article is to provide management teams in other laboratories with a description of the planning and implementation process and offer suggestions for those contemplating a similar program.

The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice.

OBJECTIVE: To evaluate the effectiveness of the AutoPap System in detecting abnormal and normal cervical smears when used in a primary screening/quality control mode, as compared with currently established laboratory practices. STUDY DESIGN: Slides were obtained prospectively and were initially processed in the routine fashion with cytotechnologist screening followed by 10% random quality control rescreening. Slides were then processed on the AutoPap System and allocated into the following groups: (1) approximately 25% of the lowest-ranking slides were placed in the laboratory's archives as within normal limits; (2) the remaining approximately 75% of slides were subjected to manual screening. Approximately 15% of the highest-ranking slides in this group underwent quality control rescreening. For each slide needing manual screening, the cytotechnologist was supplied with a report giving the ranking score of that slide. All discrepant slides for either adequacy or diagnosis were subjected to a truth-determination process. The results obtained from the two arms of the protocol were then compared. RESULTS: The AutoPap System-assisted arm of the study was superior to the current practice arm for the identification of abnormal slides at the level of atypical squamous cells of undetermined significance and above (ASCUS+), low grade squamous intraepithelial lesion (LSIL) and higher LSIL+. AutoPap System-assisted practice was equivalent to current practice for the identification of unsatisfactory and satisfactory but limited by slides. All results showed statistical significance. In addition, AutoPap System-assisted practice in the study indicated improved specificity of diagnosis. CONCLUSION: AutoPap System-assisted practice shows superior sensitivity and specificity when compared to current practice. Its clinical use as a primary screening device should improve the overall practice of cervical cytology as well as provide potential enhancement in overall laboratory productivity.

Time interval effect on repeat cervical smear results.

OBJECTIVE: Second cervical smears obtained at short time intervals often exhibit a lesser degree of abnormality than the first smear. We studied the effect of time interval between smears on diagnoses in two large, distinctive cohorts. STUDY DESIGN: Patients with two or more satisfactory smears with at least one smear or a cervical biopsy showing atypical squamous cells of undetermined significance or greater were selected. Patients were divided into four subsets by test intervals (days) (< or = 45, 46-90, 91-120, > 120) and compared statistically. RESULTS: The distribution of differences between results for the short-interval subsets (< 120) was significantly different (P < .01) from the interval subset > 120 days. At short intervals the results revealed loss of sensitivity in the second smear as compared to the initial smear and concurrent biopsies. CONCLUSION: Rapidly repeated cervical smears show poor agreement with the biopsy and may be misleading. This effect is most pronounced when the interval is < 45 days. Colposcopists should consider whether concurrent smears shortly after an abnormal smear are worth performing, given the loss of sensitivity.

Implementing complex networking laboratory information systems in a health maintenance organization.

Kaiser Permanente, Northern California Region (KPNCR) currently consists of 17 medical centers and 28 medical office building clinical laboratories plus a large, centralized reference laboratory. Before 1977, KPNCR processed laboratory information manually. With the opening of the Kaiser Permanente Regional Laboratory in Berkeley in 1977, a card punch system was used to capture that laboratory's data. In 1985, the Regional Laboratory installed a mini-mainframe system. In 1990, KPNCR Implemented a Region-wide Integrated Laboratory Information System. The software used was manufactured by Cerner Corporation, Kansas City, Missouri. The hardware platform consisted of for DEC VAXs. The decision was based on flexibility, supportability, and well established customer base. Work on the database began in September of 1991. The first "go-live" was in August of 1992. All facilities--46 laboratories--were "live" by February of 1995. Total implementation time was 27 months.