Proficiency testing in cytology laboratories in Ontario, Canada: a decade of experience. II. Results of initial surveys

The results of the initial surveys in the cytology proficiency testing of the medical laboratories in the Province of Ontario, Canada, showed a high correlation between the opinions of the testing committee and the participants in the categories of "no abnormal cells," "metaplasia" and forms of "benign atypia." The proportion of times that slides were tested in the categories of dysplasia and malignancy in the surveys increased from 38% by the end of survey 3 to 46% by the end of survey 5. A progressive improvement in the diagnostic accuracy was demonstrated in the categories of malignancy and severe dysplasia while results were more variable in the categories of moderate and mild dysplasia. Several educational activities were initiated following survey 3, including development and circulation of demonstration sets of marked glass slides for repeated circulation to participants as well as copies of a slide/tape presentation describing the program and specific case material.     

Toward implementation of a regional quality assurance program in cytopathology: the Hong Kong experience

OBJECTIVE: To develop a local quality assurance program in cytopathology based on circulation of patient specimens on glass slides, with limited resources. STUDY DESIGN: A working group was set up for design and running of the program. Participation is on a laboratory basis. The scope and frequency of testing are defined. Well-documented cases (including gynecologic, nongynecologic and fine needle aspiration cytology) with commonly encountered diagnoses are collected. Consensus concerning the diagnosis, interpretive menu and scoring system is sought before the actual slide circulations using express mail. After returning their answers to the program organizer, the participating laboratories receive immediate feedback on their scores, with reference answers, explanatory notes, "whole-mount" images of glass slides and cumulative responses of peer laboratories for on-site checking. At the end of each year, an electronic file containing representative photomicrographs of all cases examined is provided to individual laboratories for their permanent records and training purposes. RESULTS: The program was launched in mid-2003. There were 24 and 27 participating laboratories from Hong Kong (and Macau) in 2003 and 2004, respectively. To date, >150 well-documented cytology cases are available in the slide pool and ready for circulation. As the revenue is mainly to cover the expenses of express mail, the program can be carried out at a relatively low cost. CONCLUSION: In order to have any cytology quality assurance program accepted by local laboratories, it has to be fair and practical. Strict confidentiality needs to be observed throughout the process. This program emphasizes both performance assessment and educational value. Adequate representation from experienced local cytology workers, detailed documentation support from authorities and assistance from dedicated staff are essential to the success of any external proficiency testing scheme. Regular review and evaluation are also necessary for continuous improvement. The Hong Kong experience can serve as an example of running a glass slide-based cytology quality assurance program in a small region with limited resources.     

Proficiency testing in cytology laboratories in Ontario, Canada: a decade of experience. III. A precision study of consistency and reproducibility in cytology reporting

The Ontario Laboratory Proficiency Testing Program's testing model and the results of early surveys of cytology laboratories have been previously described. To test consistency and accuracy, the same slides from one survey were recirculated to the same laboratory in the next survey. There was no statistical difference in either the accuracy or consistency in reporting by the various categories of personnel. Analysis of the data by category of diagnosis showed the reporting of "no abnormal cells" and "benign atypia" to be slightly more accurate and "moderate dysplasia" and "severe dysplasia" to be slightly less accurate than the reporting in other categories. Consistency in reporting appeared to be slightly less accurate in severe dysplasia than in the other categories. The analysis, which includes the results from all licensed cytology laboratories in Ontario, provides evidence that, in the reporting of cervical cytologic material, it is feasible to differentiate among the various categories within the spectrum of squamous epithelial abnormalities with a general level of accuracy and consistency that, although satisfactory, is not yet ideal.     

Proficiency testing in cytology in New York. Analysis of a 14-year state program

A review of the first 14 years of the New York State Proficiency Testing Program in cytology shows the value of external quality-control evaluation based upon an established standard of performance as a prerequisite for licensure by a regulatory agency. Performance by participating laboratories has improved over the 14-year period. Hospital and independent laboratories had a higher pass rate than did state-run laboratories. Laboratories that did not employ cytotechnologists and performed fewer than 1,000 tests annually tended to have the lowest pass rates and consequently to undergo the most training before retesting and licensing. Overall, the predominant type of error, regardless of specimen type, was false negatives (underreads). Cervicovaginal false-negative errors by cytotechnologists ranged from 2% to 8%; such errors by cytopathologists ranged from 2.1% to 6.9%. Deficiencies and weaknesses detected by proficiency testing were remedied through a combination of surveillance and education.     

Scientific issues related to the cytology proficiency testing regulations

The member organizations of the CETC feel strongly that there are significant flaws associated with the proposed proficiency test and its implementation. The most immediate modifications include lengthening the required testing interval, utilizing stringently validated and continuously monitored slides, changing the grading scheme and changing the focus of the test from individuals to laboratory level testing, as described above. Integration of new computer-assisted and location-guided screening technologies into the testing protocol is necessary for the testing program to be compliant with the current CLIA law. The regulation also needs to be flexible enough to accommodate new technologies that are implemented in laboratory practice, education and administration of the test. The changes recommended in this document address the most immediate technical and scientific concerns with the current implementation of PT for gynecologic cytology. The CETC will be submitting a subsequent document, following full review of the current regulations, with recommendations for changes, justifications and impact.     

Opportunistic testing of medically underserved women for cervical cancer in South Africa

OBJECTIVE: To determine the yield of opportunistic Pap smears taken in an unscreened and medically underserved population in the Transkei Region of South Africa. STUDY DESIGN: Cross-sectional study of 22,160 cervical cytology specimens from an unscreened population attending gynecologic outpatient clinics between January 1990 and December 1996. RESULTS: The overall prevalence of atypical squamous cells of uncertain significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL) was, respectively, 34.7%, 8.3% and 2.4%. The ASCUS: SIL ratio was 3:1. The prevalence of invasive squamous cell carcinoma was 1.6%. The yield of opportunistic Pap smears was 10.7% including only LSIL and HSIL. CONCLUSION: The pathologic process of precursor lesions of cervical cancer appears to start at an early age since > 20% of cases are diagnosed before the age of 30 years. In the absence of a national screening program, opportunistic testing of medically underserved women needs to be maintained and encouraged.     

Canadian experience in cytology proficiency testing

The mandatory Laboratory Proficiency Testing Program (LPTP) of the province of Ontario as applied to cytology laboratories is briefly described. LPTP evaluates reporting of test slides to identify laboratories that have deficiencies. Such laboratories receive an on-site visit, followed by recommendations on means of improvement (especially educational) and subsequent monitoring. Most of the 18 cytology laboratories visited to date have shown an improved level of performance on later tests.     

Screening for the prevention of cervical cancer in the era of human papillomavirus vaccination: an Australian perspective

Australia has a unique and highly successful screening program for cervical cancer which is based on the conventional Pap smear. Since its introduction in 1991 there has been a decline in both the incidence of and mortality from this disease. Part of the success of this program has been the introduction of Pap test registers and strict quality assurance measures for cervical cytology, including compulsory key performance indicators for laboratories. Using these measures, nationwide calculations give cervical cytology in Australia a sensitivity of 78% for high-grade lesions and a positive predictive value (PPV) of 78%. Australia was the first country to introduce a widespread government-funded human papillomavirus (HPV) vaccination program in 2007. Because of the high accuracy of Australian cytology, HPV testing alone, given its low PPV and high cost, is unlikely to be a viable alternative to cytology for primary screening in this country. Australia therefore faces unique issues and choices in integrating its extensive vaccination program with a successful cervical screening program.     

Laboratory performance in a food microbiology proficiency testing scheme.

Results from two shipments in a proficiency testing scheme in which almost 200 food microbiology laboratories participated are summarized. Freeze-dried mixtures of bacteria were used as simulated food samples. Four and six samples, respectively, were examined. The statistical procedures used to evaluate the performance of participating laboratories are described. It is shown that laboratories which had been in the scheme for a long time perform, on average, better than those that had been in the scheme for a short time. The former laboratories produced fewer false and outlying results, and were more accurate and precise in their determinations.     

Cervical cytology quality assurance in Washington State.

The objectives of this study were to establish a profile of cervical cytology laboratories in Washington State, identify quality assurance problems amenable to correction through education or legislation, and describe differences between large and small cytology laboratories. All 43 Washington laboratories that perform cervical cytology were surveyed by mail during 1989. Completed surveys were returned by 37 (86%) of the laboratories. Nearly half (43%) of the respondents reported processing less than 10,000 Papanicolaou smears annually. Only one-third (35%) of the respondents reported participating in relevant proficiency programs. A proportion of smaller cytology laboratories were compensating their cytotechnologists on the basis of the number of slides read and allowing Papanicolaou smears to be read outside the confines of the laboratory. The results of this study suggest that cytotechnologists in some larger Washington laboratories have been exceeding work load limits recommended by professional associations. Recent legislation includes regulations that address cervical cytology quality assurance. However, continued efforts will need to be made to encourage voluntary adoption of quality control measures not addressed by this legislation.     

Diagnostic performance of United States Air Force cytology laboratories. An eight-year experience in central monitoring

Based on experience obtained through review of historical case material, the cytology program of the United States Air Force was regionalized into ten cytocenters, which annually process approximately 375,000 gynecologic cases. In order to assure uniformity and quality of diagnosis to multiple supplying clinics, standardized diagnoses were developed with required central reporting of all abnormal recovery rates. Initial results showed a sign-out abnormal rate (class II or worse) ranging from 1% in two cytocenters to nearly 6% in two others--over a fivefold variation on a demographically similar population. Variation by diagnostic class and follow-up tissue biopsies are reported to validate the higher abnormal rates. Through an applied program over the last seven years of formal education of pathologists and cytotechnologists, consultative visits and sharing of comparative referred statistics, the subsequent abnormal rates were substantialy altered to a range of 3.5% to 7.0%. More recently, required reporting of abnormal rates per technologist appears to be another monitor of laboratory quality, in that a given cytocenter may have a total abnormal rate of 4.5%, but a range among cytotechnolgists of 1.3% to 8.7%. These and other presented statistics may prove valuable for external monitoring (including assessment of quality performance) of individual cytology laboratories.     

Enhancing recovery of endocervical component on gynecologic cytology specimens processed by thin-layer technology

OBJECTIVE: To address the causes and report the corrective measures required for resolving the initial problem of high rates of cervical vaginal cytology specimens reported as having no endocervical component on SurePath (AutoCyte, Inc., Burlington, North Carolina, U.S.A.) liquid-based, thin-layer technology at an academic center cytology laboratory. STUDY DESIGN: Analysis of 511 cases lacking endocervical/transformation zone component out of 9,221 SurePath thin-layer gynecologic specimens processed in a one-year period. The study encompassed a review of sample collection techniques by physicians and nurses, specimen processing, cytologic features of endocervical/squamous metaplastic cells processed by the SurePath method and statistical analysis of endocervical cell recovery rates after implementation of corrective measures. RESULTS: Absence of endocervical/transformation zone component varied from an initial 18% in the first month to an average of 5.3% after corrective actions were implemented. Current rates of SurePath thin-layer specimens having no endocervical component are lower than those for conventional smears. CONCLUSION: Since SurePath was only recently introduced to the market, there are no previously published data addressing how to optimize the recovery of endocervical component on liquid-based, thin-layer specimens processed by this methodology.     

Laboratory performance in a food microbiology proficiency testing scheme

Results from two shipments in a proficiency testing scheme in which almost 200 food microbiology laboratories participated are summarized. Freeze-dried mixtures of bacteria were used as simulated food samples. Four and six samples, respectively, were examined. The statistical procedures used to evaluate the performance of participating laboratories are described. It is shown that laboratories which had been in the scheme for a long time perform, on average, better than those that had been in the scheme for a short time. The former laboratories produced fewer false and outlying results, and were more accurate and precise in their determinations.     

National registry of cervical cytologic diagnoses in The Netherlands

The national cervical cytology registry being developed in the Netherlands is described. A large-scale screening program for cervical cancer has been in effect since 1975 in the region of the cities of Nijmegen, Utrecht and Rotterdam. At the start of the pilot projects, laboratories agreed upon a uniform protocol for reporting cytologic findings and recommendations for follow-up examinations in cases of abnormalities. Based on the results of the three pilot projects, in 1985 the Dutch government decided to organize a nationwide screening program for cervical cancer. All pathology laboratories involved in this national screening program are using the same screening protocol and the same coding system for cytologic and histologic diagnoses. By the end of 1989, all pathology laboratories will be linked to a central pathology diagnosis data base (PALGA). Linkage of screening results to previous and follow-up cytologic and histologic findings will enable epidemiologic studies on a regional or national level. Each physician who has submitted specimens will, next to the cytology reports, periodically receive reviews of the number of smears submitted, the cellular composition (quality) of those smears and the follow-up findings. The execution of requests for follow-up examination will be supervised by the participating pathology laboratories. The national cervical cytology registry will enable registration of all relevant cytologic and histologic diagnoses in a uniform way, but will also establish a unique high-quality national data bank, which will be of great value in the analysis of the effectiveness of the national screening program for cervical cancer. It will enable measurement of the impact of various screening protocols and give insight into the behavior of cervical cancer and the progressive or regressive character of its early stages. It will also offer the opportunity to initiate and evaluate quality control protocols.     

Development and challenge of HIV/AIDS testing laboratory network and quality assurance system in China

This paper describes the development and challenge of HIV/AIDS testing laboratory network and quality assurance system in China. At present, the HIV/AIDS testing laboratories includes three classes, the National AIDS Reference Laboratory, HIV/AIDS confirmatory laboratories and HIV/AIDS screening laboratories. All of them are accredited by the health authorities, and each class of laboratories take charge of their function strictly according to the “National Management of HIV/AIDS Detection (2006)”. A complete quality assurance and quality control system for HIV/AIDS testing has been developed, which includes technical training, strict laboratory monitoring and approval, examination or proficiency testing on HIV/AIDS detection, and quality evaluation and supervision of HIV/AIDS diagnostic kits. Besides conduct the routine anti-HIV antibody test, more and more laboratories began to conduct other tests, such as CD4⁺T lymphocyte cell counting, HIV viral load, HIV DNA PCR, genotyping, drug resistance, and HIV-1 recent infection test. The primary challenges faced by the HIV/AIDS testing laboratory network are in the areas of laboratory management and quality control. For example, the provincial PT program is inefficient, the internal quality control is conducted perfunctorily, personnel training can not met the needs of the workplace, which need to be improved. Foundation item: MOH Program on Applied Research in the Prevention and Treatment of AIDS (WA 2003-17)     

Comparative analysis of a liquid-based Pap test and concurrent HPV DNA assay of residual samples. A study of 608 cases

OBJECTIVE: To retrospectively study the HPV DNA assay of residual samples from the ThinPrep Pap Test (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) PreserveCyt (Cytyc) vial as a quality improvement (QI) indicator for management of patients with abnormal cervical cytology. STUDY DESIGN: Six hundred eight residual sample vials of liquid-based Pap-Test specimens were selected for the study based on Pap-test results from October 1998 to March 2001. The specimen vials were forwarded to the reference laboratory (American Medical Laboratories, Chantilly, Virginia, U.S.A.) for HPV DNA assay using the Hybrid Capture System method (Digene Corporation, Gaithersburg, Maryland, U.S.A.). At the time of HPV DNA assay, the residual samples were between 8 days to 10 months old, and each vial contained 4 mL. Of the 608 study cases, 76 were WNL, 115 contained BCC, 172 contained ASCUS, 179 were LSIL and 66 were HSIL. In this study, the 191 WNL and BCC cases were designated as the disease-free control group. The HPV DNA typing results were reported as low-risk, high/intermediate-risk or HPV DNA "not detected" HPV types. The HPV DNA testing results were compared to the Pap-Test diagnoses and statistical analysis performed. RESULTS: The following information reflects the percentage of HPV DNA-positive cases based on the Pap-Test diagnoses: 16.2% in WNL and BCC, 51.1% in ASCUS, 94.4% in LSIL and 98.4% in HSIL. Sensitivity (95.5%), specificity (83.7%), false negative value (4.4%), false positive value (16.2%) and predictive value of a positive (88.3%) and negative (93.5%) Pap-Test were calculated on the basis of HPV DNA testing results for 436 cases that were diagnosed as either SIL or negative (WNL and BCC). ASCUS (172) Pap-Test cases were considered borderline--disease positive and excluded from statistical analysis. CONCLUSION: The HPV DNA assay of residual samples from ThinPrep Pap-Test liquid-based specimens is an objective adjunct to the gynecologic cytology QI protocol and is the gold standard reference test for triaging women with equivocal cytologic diagnoses. The great value of HPV DNA testing is its high sensitivity (95.5%), specificity (83.7%) and negative predictive value (93.5%). HPV DNA testing results can be used as a tool to better determine the need for referrals for colposcopic biopsy, especially for patients with an ASCUS diagnosis. The residual Pap-Test specimens are stable and reproducible for HPV DNA typing. A working flow chart for our gynecologic cytology QI program was produced from the Pap-Test and HPV DNA assay results. This offer presents the added benefit of minimizing the problem of sample variation. The prevalence of HPV infection was 16.2% in this study.     

HPV testing for cervical cancer screening in Croatia

Opportunistic screening based on the Pap smear has been undertaken in Croatia since 1953. However, cervical cancer remains an important health problem in Croatia when compared to European countries with organised screening programmes. In Croatia, in addition to screening based on well established cytology, Human papillomavirus (HPV) testing is widely used as secondary test as a triage to borderline cytology and as a follow-up after treatment of severe cervical lesions. Many different approaches for HPV testing arose in Croatia over the last decade depending on the needs of each medical institution involved. Presently, there is an urgent need for better networking between the laboratories, the implementation of quality assessment and the adaptation of a uniform system of referring to and reporting of HPV testing. In conclusion, the best possible organisation for HPV testing would be essential for implementation of HPV testing as primary screening test in Croatia, an thus ultimately and hopefully, the more successful cervical cancer control.     

Molecular genetic testing in the United States: comparison with international practice

OBJECTIVE: To compare data on the practices of molecular genetic testing (MGT) in laboratories in the United States with those in 18 other countries. METHODS: A Web-based survey of MGT laboratory directors (n = 827; response rate 63%) in 18 countries on three continents was carried out, and the response from U.S. laboratories compared to all others. Quality assurance and reporting indices were developed and calculated for each responding laboratory. RESULTS: A comparison of U.S. results with all other countries identified differences in laboratory setting, personnel qualifications, and the specific tests being offered, but similar rates of adherence to MGT quality standards and reporting practices were found. The survey also documented substantial transborder flow of specimens, most commonly due to the lack of availability of the test in the United States or because the test was available only through a research protocol, highlighting the need for common reporting and practice guidelines for the international MGT community. CONCLUSION: The findings presented here provide further support for the need to consider the application of the Organisation for Economic Cooperation and Development (OECD) Guidelines and the establishment of compatible accreditation programs or equivalent mechanisms across national borders to ensure the quality of laboratory services and the clinical usefulness of molecular genetic test reports for referred specimens.     

Recommendations for lipid testing and reporting by Australian pathology laboratories

The importance of measuring blood lipids in determining the absolute risk of a cardiovascular event is now well established. In Australia, the National Heart Foundation of Australia and the Cardiac Society of Asutralia and New Zealand (NHFA/CSANZ) have done much to educate doctors. In recent years the recommendations of the NHFA/CSANZ have been based on values for Low-density lipoprotein (LDL-C) as well as High-density lipoprotein cholesterol (HDL-C) and Triglyceride (TG). This change has been reflected in requests to pathology laboratories. However the interpretation of these results may be difficult and the NHFA guidelines outline desirable values for patients at high risk only. There are no formal recommendations for reference intervals or interpretive comments. With the availability of expert systems, some pathology laboratories are now in a better position to provide specific comments to assist with the interpretation of test results.An ad hoc committee of private and public chemical pathologists met to draft recommendations for lipid testing and reporting by Australian pathology providers, on the basis of current guidelines and their own expertise. Provisions in the current Medicare Benefits Schedule (MBS) for lipid testing were reviewed, and the indications for lipid testing, recommended tests, the logistics of managing specimens, methods of analysis and availability of specialised tests have been documented. Recommendations are made on the provision of desirable values for lipid tests. Suggestions are provided on interpretive comments which could accompany reports of lipid test results, including categorisation of the likely associated lipoprotein abnormalities, their causes, contribution to risk for cardiovascular disease (CVD) and targets for treatment. Current and future approaches to the assessment of risk for CVD are discussed.