Navigating Practice Issues Related to the Unsatisfactory Cervicovaginal Papanicolaou Test: Survey Results of Laboratories Participating in the 2020 College of American Pathologists PAP Education Program.

CONTEXT.­: Unsatisfactory Papanicolaou (Pap) tests pose a unique set of challenges to the laboratory with regard to their processing, review, reporting, and performance of human papillomavirus (HPV) testing. There are no standardized guidelines for the review process and handling of unsatisfactory Pap tests. OBJECTIVE.­: To assess the current practice patterns regarding various aspects of the unsatisfactory Pap test, from processing to reporting, across laboratories worldwide. DESIGN.­: A supplemental questionnaire was mailed to laboratories participating in the 2020 College of American Pathologists (CAP) Gynecologic Cytopathology (PAP Education) Program, requesting data regarding the unsatisfactory Pap test. RESULTS.­: Of 1520 participating laboratories, 619 (40.7%) responded, and the responses of 577 laboratories were included for further analysis. Only 64.6% (373 of 577) laboratories used the unsatisfactory Pap test criteria as specified by the 2014 Bethesda System. About three-quarters of the respondents (433 of 576; 75.2%) routinely rescreened unsatisfactory Pap tests. Routine repreparation of such Pap tests was performed by 54.9% (316 of 576) of laboratories, and 52.0% (293 of 563) used glacial acetic acid for repreparing excessively bloody specimens. HPV test results were reported for unsatisfactory Pap tests, always or sometimes, by 62.4% (353 of 566) of respondents. CONCLUSIONS.­: This CAP survey reveals important information regarding the practice patterns pertaining to several aspects of the unsatisfactory Pap test. It also provides valuable insight into the quality assurance measures that can be implemented for such tests. Future studies can further aid in the standardization of all components of the handling of unsatisfactory Pap tests for overall quality improvement.

The Implementation of Nongynecologic Reporting Systems in Cytopathology Laboratories Is Highly Variable: Analysis of Data From a 2020 Supplemental Survey of Participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT­: In recent years, several reporting systems have been developed by national and international cytopathology organizations to standardize the evaluation of specific cytopathology specimen types. OBJECTIVE­: To assess the current implementation rates, implementation methods, and barriers to implementation of commonly used nongynecologic reporting systems in cytopathology laboratories. DESIGN­: Data were analyzed from a survey developed by the committee and distributed to participants in the College of American Pathologists Nongynecologic Cytopathology Education Program mailing. RESULTS­: Nongynecologic reporting systems with the highest rate of adoption were the Bethesda System for Reporting Thyroid Cytopathology, 2nd edition (74.1%; 552 of 745); the Paris System for Reporting Urinary Cytology (53.9%; 397 of 736); and the Milan System for Reporting Salivary Gland Cytopathology (29.1%; 200 of 688). The most common reason given for not adopting a reporting system was satisfaction with a laboratory's current system. Implementation varied among laboratories with regard to which stakeholders were involved in deciding to implement a system and the amount of education provided during the implementation process. CONCLUSIONS­: The implementation of nongynecologic reporting systems in cytopathology laboratories was highly variable.

Cross-contamination in cytology processing: a review of current practice.

INTRODUCTION: New cytopreparatory technologies decrease the need for direct smears in favor of an increased use of liquid-based cytology methods. Despite these practice changes, Clinical Laboratory Improvement Amendments continue to require that cytopathology laboratories have procedures to prevent cross-contamination (CC). While the incidence of CC is not well documented, specific cytologic preparations and specimens with a high potential for CC have not been generally defined by professional guidelines or consensus. The American Society of Cytopathology Clinical Practice Committee surveyed cytology practitioners to better understand current practice related to CC in cytology. MATERIALS AND METHODS: The survey focused on four topics: (1) practice settings and demographic data; (2) current practice for meeting CC requirements; (3) practice for rapid on-site evaluation; and (4) preparation types considered high risk for CC. The survey was sent to all American Society of Cytopathology and American Society for Cytotechnology members from July 1 to August 14, 2020. RESULTS: Ninety-eight percent of laboratories had a written CC policy, with 66.18% of the policies addressing rapid on-site evaluation CC procedures. Documented cases of CC were rare. Alcohol-fixed, direct smears of Pap-stained fluids were deemed the most likely to be impacted by CC. Cell block contamination during the histologic processing were reported by 56.20% of respondents. CONCLUSIONS: Changes in practice has resulted in decreased preparation types associated with a high potential for CC. Laboratories should follow a risk-based approach to define these cases. Knowledge of practice patterns among laboratories can guide the development and refinement of policy and procedures.

Perspectives on Expanded Scope of Practice in Cytotechnology.

INTRODUCTION: In an effort to identify professional trends while offering meaningful resources to support decision making in the cytopathology community, the ASC/ASCP Workgroup: Focusing on Emerging Roles in Cytopathology conducted several data collection activities to assess the current state and professional trends of cytotechnologist (CT) practice. This information is intended to inform evidence- based development of education and workforce model(s). MATERIALS AND METHODS: Research was conducted through mixed-method data collection processes. These included the ASCP Board of Certification (BOC) Practice Analysis, focus groups used to gather qualitative data regarding the perceptions and experiences of current stakeholders in cytopathology through face-to-face discussion, and a RAND Delphi study conducted to gather qualitative data regarding the perspectives and "pulse" of decision makers influencing cytopathology practice. RESULTS: Research findings reveal that practice patterns with new and emerging technologies are changing the workplace for many cytotechnologists. Cytotechnologists are increasingly performing tasks within the laboratory that extend beyond their formal training and are looking to professional societies to bridge the gap. Although many laboratory leaders embrace the use of cytotechnologists in expanded roles, regulatory restrictions and reimbursement rules are among acknowledged barriers to change. CONCLUSIONS: This study examines current marketplace needs and cytotechnologists' perceptions of their evolving workplace demands through qualitative data collection. This study provides a snapshot of the cur- rent climate of cytopathology and data that will help direct future education, personnel training needs, and staffing decisions.

Changing Practice Patterns for Cytotechnologists: A Comparative Analysis of Data from the 2009 and 2015 ASCP BOC Practice Analysis Surveys.

BACKGROUND: The American Society for Clinical Pathology (ASCP) Board of Certification (BOC) surveys US certified cytotechnologists (CTs) at approximately 5-year intervals to gain information about current practice patterns. Although the purpose of this survey is to inform valid content development for the BOC CT examination, comparative longitudinal analysis of the survey data provides information about changes in cytotechnology practice. MATERIALS AND METHODS: BOC Practice Analysis Survey data for 2009 and 2015 were examined, comparing survey demographics and performance of laboratory tasks. The 2015 survey added tasks not previously surveyed and considered them emerging when performed by a majority of respondents. RESULTS: Two hundred thirty-five participants completed the survey in 2015 and 151 in 2009. Respondents reported an overall decrease in performing conventional Papanicolaou tests (-25.3%). Respondents reported increases in morphologic tasks such cytologyehistology correlation (17.5%), cell-block interpretation (17.5%), and preliminary interpretation of histochemical stains (e.g., mucin and Grocott's methenamine silver stain) (16.7%), as well as quality assurance tasks. Majority-performed, newly surveyed tasks included touch prep preparation (57.8%) and interpretation (59.2%) and ancillary test triage (59.6%). Molecular tasks such as tumor identification (6.8%) and preparation of cytology specimens for oncology molecular testing (9.4%) did not meet majority reporting thresholds. CONCLUSIONS: Although performance of the Papanicolaou test is declining, CTs report increases in additional morphologic as well as other laboratory tasks. Emerging tasks (2015) focus on FNA specimens. Knowledge of cytology practice patterns will help guide development of education and training resources toward maintaining an appropriately trained workforce.

Changing practice patterns for cytotechnologists: a comparative analysis of data from the 2009 and 2015 ASCP BOC Practice Analysis Surveys.

BACKGROUND: The American Society for Clinical Pathology (ASCP) Board of Certification (BOC) surveys US certified cytotechnologists (CTs) at approximately 5-year intervals to gain information about current practice patterns. Although the purpose of this survey is to inform valid content development for the BOC CT examination, comparative longitudinal analysis of the survey data provides information about changes in cytotechnology practice. MATERIALS AND METHODS: BOC Practice Analysis Survey data for 2009 and 2015 were examined, comparing survey demographics and performance of laboratory tasks. The 2015 survey added tasks not previously surveyed and considered them emerging when performed by a majority of respondents. RESULTS: Two hundred thirty-five participants completed the survey in 2015 and 151 in 2009. Respondents reported an overall decrease in performing conventional Papanicolaou tests (-25.3%). Respondents reported increases in morphologic tasks such cytology-histology correlation (17.5%), cell-block interpretation (17.5%), and preliminary interpretation of histochemical stains (e.g., mucin and Grocott's methenamine silver stain) (16.7%), as well as quality assurance tasks. Majority-performed, newly surveyed tasks included touch prep preparation (57.8%) and interpretation (59.2%) and ancillary test triage (59.6%). Molecular tasks such as tumor identification (6.8%) and preparation of cytology specimens for oncology molecular testing (9.4%) did not meet majority-reporting thresholds. CONCLUSIONS: Although performance of the Papanicolaou test is declining, CTs report increases in additional morphologic as well as other laboratory tasks. Emerging tasks (2015) focus on FNA specimens. Knowledge of cytology practice patterns will help guide development of education and training resources toward maintaining an appropriately trained workforce.

Perspectives on expanded scope of practice in cytotechnology.

INTRODUCTION: In an effort to identify professional trends while offering meaningful resources to support decision making in the cytopathology community, the ASC/ASCP Workgroup: Focusing on Emerging Roles in Cytopathology conducted several data collection activities to assess the current state and professional trends of cytotechnologist (CT) practice. This information is intended to inform evidence-based development of education and workforce model(s). MATERIALS AND METHODS: Research was conducted through mixed-method data collection processes. These included the ASCP Board of Certification (BOC) Practice Analysis, focus groups used to gather qualitative data regarding the perceptions and experiences of current stakeholders in cytopathology through face-to-face discussion, and a RAND Delphi study conducted to gather qualitative data regarding the perspectives and "pulse" of decision makers influencing cytopathology practice. RESULTS: Research findings reveal that practice patterns with new and emerging technologies are changing the workplace for many cytotechnologists. Cytotechnologists are increasingly performing tasks within the laboratory that extend beyond their formal training and are looking to professional societies to bridge the gap. Although many laboratory leaders embrace the use of cytotechnologists in expanded roles, regulatory restrictions and reimbursement rules are among acknowledged barriers to change. CONCLUSIONS: This study examines current marketplace needs and cytotechnologists' perceptions of their evolving workplace demands through qualitative data collection. This study provides a snapshot of the current climate of cytopathology and data that will help direct future education, personnel training needs, and staffing decisions.

Current practice patterns in nongynecologic and fine-needle aspiration cytology.

INTRODUCTION: The American Society of Cytopathology Clinical Practice Committee in collaboration with the American Society of Cytotechnology surveyed cytology practitioners to better understand current practices related to nongynecologic (NGYN) cytology. While work practices in gynecologic (GYN) cytology are highly regulated with limited variation among specimens and processing techniques, practice patterns for NGYN cytology are less standardized among laboratories. MATERIALS AND METHODS: An NGYN cytology survey was created that consisted of 40 questions focusing on 6 main topic areas: (1) practice settings and demographic data; (2) NGYN non-fine-needle aspiration cytology; (3) fine-needle aspiration (FNA) cytology; (4) rapid on-site evaluation practices; (5) workload recording practices; and (6) expanding roles of the cytotechnologist (CT). The survey was sent to all American Society of Cytopathology and American Society of Cytotechnology members and remained available for 40 days. RESULTS: There were 368 survey participants (14% response rate) with nearly equal participation among CTs, cytology general managers and/or supervisors, and pathologists representing a variety of practice types. Most laboratories (87%) are providing a rapid on-site evaluation service for FNA specimens. The role of CTs is expanding with the majority of respondents stating that CTs assist with both clinician-performed and pathologist-performed FNA acquisition (77% and 50%, respectively), telecytology (16%), and screening of ancillary studies, including special stains (64%), immunohistochemistry (23%), and fluorescence in situ hybridization (16%). CONCLUSIONS: Knowledge of NGYN cytology practice patterns among laboratories may contribute information to better define the future of cytotechnology, support reimbursement initiatives, and enhance quality and efficiencies in the cytology laboratory.

Constructing a modern cytology laboratory: A toolkit for planning and design.

INTRODUCTION: Constructing or renovating a laboratory can be both challenging and rewarding. UAB Cytology (UAB CY) recently undertook a project to relocate from a building constructed in 1928 to new space. UAB CY is part of an academic center that provides service to a large set of patients, support training of one cytotechnology program and one cytopathology fellowship training program and involve actively in research and scholarly activity. Our objectives were to provide a safe, aesthetically pleasing space and gain efficiencies through lean processes. METHODS: The phases of any laboratory design project are Planning, Schematic Design (SD), Design Development (DD), Construction Documents (CD) and Construction. Lab personnel are most critical in the Planning phase. During this time stakeholders, relationships, budget, square footage and equipment were identified. Equipment lists, including what would be relocated, purchased new and projected for future growth ensure that utilities were matched to expected need. A chemical inventory was prepared and adequate storage space was planned. Regulatory and safety requirements were discussed. Tours and high level process flow diagrams helped architects and engineers understand the laboratory daily work. Future needs were addressed through a questionnaire which identified potential areas of growth and technological change. Throughout the project, decisions were driven by data from the planning phase. During the SD phase, objective information from the first phase was used by architects and planners to create a general floor plan. This was the basis of a series of meetings to brainstorm and suggest modifications. DD brings more detail to the plans with engineering, casework, equipment specifics, finishes. Design changes should be completed at this phase. The next phase, CD took the project from the lab purview into purely technical mode. Construction documents were used by the contractor for the bidding process and ultimately the Construction phase. RESULTS: The project fitted out a total of 9,000 square feet; 4,000 laboratory and 5,000 office/support. Lab space includes areas for Prep, CT screening, sign out and Imaging. Adjacent space houses faculty offices and conferencing facilities. Transportation time was reduced (waste removal) by a Pneumatic Tube System, specimen drop window to Prep Lab and a pass thru window to the screening area. Open screening and prep areas allow visual management control. Efficiencies were gained by ergonomically placing CT Manual and Imaging microscopes and computers in close proximity, also facilitating a paperless workflow for additional savings. Logistically, closer proximity to Surgical Pathology maximized the natural synergies between the areas. CONCLUSIONS: Lab construction should be a systematic process based on sound principles for safety, high quality testing, and finance. Our detailed planning and design process can be a model for others undertaking similar projects.

Trends in pancreatic pathology practice before and after implementation of endoscopic ultrasound-guided fine-needle aspiration: an example of disruptive innovation effect?

CONTEXT: Little has been reported on changes in pancreatic pathology practice after implementation of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). OBJECTIVES: We assessed the impact of EUS-FNA on cytologic diagnosis replacing histologic diagnosis for pancreatic disease and determined whether it fulfills Christensen criteria of a disruptive innovation effect. DESIGN: Pattern of utilization during 20 years, diagnostic categories, and diagnostic accuracy of pancreatic cytology were compared before and after implementation of EUS-FNA. The disruptive effect of cytology relevant to biopsy was assessed by comparing the utilization trends and the accuracy of diagnosis over time. RESULTS: The mean annual volume (standard deviation) of cytologic specimens increased from 24 (11) to 231 (10) after implementation of EUS-FNA, and that of histologic specimens increased from 97 (42) to 377 (148). The average percentage of annual cases managed by following cytology alone was 19% (10) before versus 51% (8) after implementation. The percentage managed by histology alone was 56% before versus 23% after implementation. Non-endoscopic ultrasound-guided fine-needle aspiration cytology decreased from 36% to 1%. Needle biopsies decreased from 7% to 1%, and other biopsy types from 29% to 9%. Unsatisfactory (7% versus 1%), atypical (16% versus 4%), and suspicious (16% versus 3%) diagnoses were significantly reduced. The accuracy of cytologic diagnosis significantly improved: the sensitivity (confidence interval) and specificity (confidence interval) for cancer diagnosis were 55% (38%-70%) and 78% (58%-89%) before versus 88% (84%-91%) and 96% (93%-98%) after implementation, respectively. CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration improved the accuracy of cytologic diagnosis, reduced the number of indeterminate diagnoses, and replaced the need for tissue biopsy. Given its cost and simplicity as compared with tissue biopsy, this trend represents a disruptive innovation effect.

The impact of implementation of the Bethesda System for Reporting Thyroid Cytopathology on the quality of reporting, "risk" of malignancy, surgical rate, and rate of frozen sections requested for thyroid lesions.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been anticipated to improve communication between pathologists and clinicians and thereby patient outcomes. In the current study, the impact of TBSRTC on various quality and outcome measures was assessed. METHODS: The current study included all patients who underwent fine-needle aspiration (FNA) of the thyroid between April 2006 and April 2009. Before implementation, the authors used generic diagnostic categories; after implementation, TBSRTC was used. Quality of reporting, diagnostic categories, rate of surgery, rates of frozen section, the "risk" of malignancy after a cytologic diagnosis, and errors before and after implementation of TBSRTC were compared using the chi-square and Fisher exact tests. Multilevel likelihood ratios and the receiver operating characteristic were used to compare the accuracy of FNA before and after implementation. RESULTS: A total of 1671 FNAs (957 obtained before and 714 obtained after implementation of TBSRTC) were obtained from 1339 patients. Of these, 301 patients (191 before and 110 after implementation) underwent subsequent surgical resection. Before implementation, the reports were more ambiguous (3.7% vs 0.5%; P < .05) and implicit (5.1% vs 2.7%; P < .05) than after implementation. The overall rate of surgery decreased after implementation of TBSRTC (24.5% vs 19.6%; P < .05). The overall risk of malignancy did not appear to be affected by implementation of TBSRTC, but it decreased significantly after a benign FNA diagnosis compared with a diagnosis of an atypical lesion or follicular neoplasm. The rate of frozen section remained unchanged. The diagnostic accuracy was not found to be significantly different before compared with after implementation of TBSRTC. CONCLUSIONS: Implementation of TBSRTC appears to improve the quality of reporting by lowering the number of ambiguous and implicit diagnoses and decreases the overall surgery rates, particularly for benign lesions, but it does not appear to have any effect on the accuracy of FNA of the thyroid, false-positive rates, or the frequency of intraoperative consultations.

Cytotechnology labor market: an update.

Based on historic data, we recently developed a model for the cytotechnology labor market that predicted shrinkage in the workforce secondary to a reduced demand for cytotechnologists that would offset any expected increase secondary to demographic changes in the number of women eligible for cervical cancer screening. In this report, we describe the comparison of our previous model with data that were available for the 2005-2009 period. As predicted, the cytotechnology workforce experienced significant shrinkage. The 2008 wage decreased when adjusted for inflation, demand shifted downward significantly, and supply shifted, in response, slightly downward. In 2009 supply (6,064 available staff) and demand (6,355 open and filled positions) were lower than those of the 2005 market.

Anal-rectal cytology: correlation with human papillomavirus status and biopsy diagnoses in a population of HIV-positive patients.

OBJECTIVES: We describe the cytological distribution of disease, correlate cytological diagnoses with human papillomavirus (HPV) DNA status and surgical biopsy diagnoses, determine if CD4 counts correlate with lesion severity, and compare anal-rectal data of HIV-infected patients (primarily men) with cervical data. MATERIALS AND METHODS: A retrospective search of the computerized database identified 118 HIV-positive patients who had anal-rectal cytology. Cytology results were compared with available follow-up data including repeat anal-rectal cytology tests, surgical biopsy, CD4 counts, and HPV DNA polymerase chain reaction-based genotyping. RESULTS: Cytological diagnoses included 3% unsatisfactory for diagnosis, 41% negative for intraepithelial lesion or malignancy (NILM), 23% atypical squamous cells of undermined significance (ASC-US), 31% low-grade squamous intraepithelial lesion (LSIL), and 2% high-grade squamous intraepithelial lesion (HSIL) (ASC-US/squamous intraepithelial lesion, 0.7:1). Two anal intraepithelial neoplasia (AIN) II, 10 AIN III, and 1 invasive squamous cell carcinoma were histologically detected (11%). The majority of AIN II was preceded by LSIL, 54%; ASC-US, 15%; and HSIL, 8%. The false-negative fraction was 23%. Sensitivity, specificity, negative predictive value, and positive predictive value were 92%, 8%, 33%, and 67%, respectively. Of those HPV tested concurrent with the first cytology specimen, 48% NILM, 78% ASC-US, and 100% LSIL were HPV positive. Mean CD4 counts (per microliter) were lower in patients with HSIL (243 [SD, 65]) compared with LSIL (400 [SD, 261]) and NILM (428 [SD, 232]). CONCLUSIONS: Anal-rectal cytology is a useful screening test. A high percentage of AIN II lesions were detected in this at-risk population, and the majority was detected following cytological abnormality.

HPV detection rate in discordant Pap tests between cytotechnologists and pathologists.

When a Pap test is referred for pathologist review, it is accompanied by the cytotechnologist's provisional interpretation. Discordant interpretations between pathologists and cytotechnologists are sometimes noted. The objective is to correlate HPV detection rate with both estimated false-negative fraction (EFNF) and ASC to SIL ratio among discordant ASC cases. ThinPrep Pap tests in which the cytotechnologists' provisional interpretations were up- or down-graded by pathologists to ASC were retrieved between January and December 2006. HPV DNA testing was performed using hybrid capture technique. EFNFs and ASC to SIL ratio were estimated for cytotechnologists and pathologists, respectively. Overall, the EFNF ratio was 3.4% and the high-risk HPV DNA detection rates in cases that were "over-" or "under-" interpreted by technologists were 0.71 and 0.40, respectively. The overall ASC to SIL ratio was 1.41 and the high-risk HPV DNA detection rates in cases that were upgraded or downgraded to ASC were 0.40 and 0.71, respectively. In conclusion, our ASC to SIL ratios and EFNF were within acceptable range. We did not observe any association between ASC to SIL ratio and HPV detection rate in cases that were upgraded or downgraded to ASC by pathologists or between EFNF ratio and HPV detection rate in cases that were "over-interpreted" (or "under-interpreted") by cytotechnologists. The HPV detection rates for ASC cases that were originally "over-interpreted" by cytotechnologists were comparable to the HPV detection rates for LSIL, whereas those that were underinterpreted were comparable to the HPV detection rate for ASC.

Impact of expected changes in national papanicolaou test volume on the cytotechnology labor market: an impending crisis.

With the new screening and treatment guidelines and the prospect of human papillomavirus vaccination for adolescents, the current total volume of Papanicolaou (Pap) tests will be significantly reduced. We used available data to assess the current supply and demand in the cytotechnology labor market and how an expected change in Pap test volume impacts this market. Cytotechnologists' data were obtained from the American Society for Clinical Pathology (ASCP) Board of Registry and the Center for Medicare and Medicaid Services. Data for wages and vacancies were obtained from American Society for Cytotechnologists and ASCP Surveys. Cytotechnology training program data were obtained from annual reports of the Cytotechnology Programs Review Committee of American Society for Cytopathology. In the current market, the demand for cytotechnologists increases by 3.6% and the supply by 4.0% each year. At any given time, there is a vacancy rate of 3%. In the coming years, the demand will decrease remarkably with a projected total demand for cytotechnologists of 5,623 instead of 8,033 by the year 2010 and of 8,538 instead of 14,146 by the year 2026. The cytotechnology market faces an impending crisis. There is a high need for prospectively collected accurate data on demand for and supply of cytotechnologists.

Significance and possible causes of false-negative results of reflex human Papillomavirus infection testing.

BACKGROUND: The objective of this study was to assess the rate and possible reasons for false-negative (FN) reflex human papillomavirus (HPV)-DNA tests. METHODS: The authors reviewed all ThinPrep cervical specimens that were submitted for reflex HPV-DNA testing using the Digene Hybrid Capture II (HC2) method from January 2002 to January 2004. Follow-up biopsies were reviewed. The results were considered HPV-FN if the HPV-DNA test was negative and the biopsy was positive for grade > or =2 cervical intraepithelial neoplasia (CIN2+), and the results were considered true positive (HPV-TP) if the HPV-DNA test was positive and the biopsy showed CIN2+. HPV-FN cases were compared with HPV-TP cases regarding the grade and extent of CIN, the number of abnormal cells on the original ThinPrep slide, and the presence of amplifiable, viral DNA on biopsy. RESULTS: In total, 1520 (66%) of 2309 patients who had diagnoses of atypical squamous cells of undetermined significance (ASCUS) were negative for HPV DNA and 789 patients of 2309 patients (34%) were positive for HPV DNA. Three hundred sixteen women (40%) who had a positive HPV-DNA test underwent a biopsy. Of those, 36 biopsies (11%) showed CIN2+ (HPV-TP), and 154 biopsies (66%) showed CIN1. Cervical tissue was available for review from 82 women who had negative HPV-DNA tests; of these, 6 tissue samples (7%) showed CIN2+ (HPV-FN), and 13 tissue samples (16%) showed CIN1. Therefore, in the total ASCUS population that was triaged with reflex HPV testing, there were at least 42 women who were diagnosed with CIN2+, for an estimated CIN2+ FN fraction of 14% (6 of 42 women). HPV-FN lesions were smaller (but the difference was not statistically significant) and shed significantly fewer abnormal cells than HPV-TP cases. Polymerase chain reaction testing for viral DNA in the biopsy was detected in 3 of 6 women who had HPV-FN results; none of those positive results demonstrated a viral type that was not included in the Digene probes. CONCLUSIONS: Although the rate of FN high-grade lesions was significantly higher than that reported in the ASCUS/Low-grade Squamous Intraepithelial Lesion Triage trial, most missed lesions were small and shed few abnormal cells. It was assumed that those lesions were either in early stages or in regressing stages, which made their clinical significance uncertain.

Impact of HPV testing, HPV vaccine development, and changing screening frequency on national Pap test volume: projections from the National Health Interview Survey (NHIS).

BACKGROUND: The frequently cited number of 50 million annual Papanicolaou cervical screening (Pap) tests performed in the US was based on the National Health Interview Survey (NHIS) of the 1980s. Since then, monumental changes have occurred. More change will soon follow when primary human papilloma virus (HPV) testing and/or HPV vaccine delivery are fully accepted and implemented. The objectives of this study were 1) to estimate the total annual Pap tests performed in the US based on recent NHIS surveys, and 2) to estimate the potential change in the total annual Pap volume produced by changing demographics, reduced screening frequency, HPV testing, and the HPV vaccine. METHODS: In the NHIS 2000 and NHIS 2005, women were asked to report the frequency of their Pap tests for the 6 years prior to the interview and to report whether they had abnormal findings. The authors analyzed the survey respondents answers to these questions by using SAS Survey Procedures (SAS Institute, NC). The results were stratified by age, and the total national volume was then extrapolated from a similarly stratified 2000 US census. The projected increase of total Pap tests for the next 25 years was determined by using the projected census data. Potential reductions of Pap tests performed secondarily to HPV testing of women >30 years old and of HPV vaccination were also determined. RESULTS: Based on NHIS 2000 and NHIS 2005, 66 million (95% CI, 65-68) and 65 million (95% CI, 64-67) Pap tests were performed in the US, respectively. Had HPV testing been performed in women older than 30 years who had both negative HPV and negative 3-year Pap tests, then 30% (95% CI, 29-32%) of Pap tests would not have been performed. If both HPV testing and vaccination are performed, the total number of Pap tests performed annually is predicted to be reduced by 43% (95% CI, 35-38%). CONCLUSIONS: Therefore, despite an expected increase in the population of women eligible for Pap tests, the total number will likely decrease substantially in the future. This, in turn, will decrease the demand for a traditionally trained cytotechnology workforce.

High-risk HPV DNA detection rate in patients with atypical squamous cells and its relationship to the atypical squamous cell: squamous intraepithelial lesion ratio.

OBJECTIVE: To determine if there is any relationship between the atypical squamous cell (ASC):squamous intraepithelial lesion (SIL) ratio and high-risk HPV DNA detection rate. STUDY DESIGN: Data on the frequency of various cytologic diagnoses for each pathologist were retrieved from 2002 to 2003. ASC:SIL ratio for each pathologist was calculated. In addition, data related to high-risk HPV detection rate was obtained during the study period. HPV DNA testing was performed using HC II (Digene, Gaithersburg, Maryland U.S.A). Cases with insufficient quantity were excluded. RESULTS: Five pathologists, with experience ranging from 2 to 15 years, reviewed Pap tests during the study period. For the entire laboratory, the ASC:SIL ratio was 2.0, and the high-risk HPV DNA detection rate in ASC specimens was 31%. For individual pathologists, ASC:SIL ratio ranged from 1.2 to 4.0 and high-risk HPV DNA detection rate from 31% to 38%. No significant correlation was noted between the ASC:SIL ratio and high-risk HP DNA detection rate. CONCLUSION: Our ASC:SIL ratios (except for 1 pathologist) and high-risk HPV DNA detection rates were within an acceptable range. We did not observe any association between ASC:SIL ratio and high-risk HPV detection rate.

Negative colposcopic biopsy after positive human papilloma virus (HPV) DNA testing: false-positive HPV results or false-negative histologic findings?

We studied histologic examination-related factors contributing to false-negative colposcopic biopsy results. Patients positive for high-risk human papillomavirus (HPV) DNA with negative cervical histologic findings were identified between January 2002 and December 2003. Three additional H&E-stained levels were obtained when the original diagnosis was confirmed on review. Patients with atypical squamous cells of undetermined significance (ASC) Papanicolaou test results, positive HPV DNA results, and negative cervical histologic findings accounted for 4.5% of all ASC smears submitted for HPV DNA testing. Slides and tissue blocks were available for 95 cases; 4% had focal HPV infection or mild dysplasia. When deeper levels were examined, 31% had clinically significant lesions: HPV infection or cervical intraepithelial neoplasia (CIN) 1, 19%; CIN 2/3, 8%; and dysplasia, not otherwise specified, 3%. Of the remaining patients, follow-up revealed squamous abnormalities in 25%. About 5% of patients with positive HPV DNA results had a negative follow-up biopsy result. "False-negative" biopsies accounted for one third of cases. Additional levels should be obtained for discrepant results. Close follow-up is crucial when the initial biopsy result is negative because a small number of patients will have squamous abnormalities in subsequent studies.

Incidence and clinical significance of morphologically benign-appearing endometrial cells in patients age 40 years or older: the impact of the 2001 Bethesda System.

BACKGROUND: The 2001 Bethesda System (TBS 2001) introduced a new diagnostic category-normal endometrial cells in women age 40 years or older (EM >or= 40). The objective of the current study was to determine whether there was any significant increase in the frequency with which this diagnosis was reported after the implementation of TBS 2001 and the clinical significance of this diagnosis. METHODS: All women who had a Papanicolaou (Pap) test and a diagnosis of EM >or= 40 between January 1999 to December 2003 were identified. Follow-up included repeat Pap tests and/or surgical pathology. TBS 2001 was implemented on January 1, 2002. RESULTS: In total, 556 Pap tests with a diagnosis of EM >or= 40 were identified, accounting for 0.52% of the 106,204 Pap tests evaluated during the study period. The incidence of EM >or= 40 before and after implementation of the new TBS was 0.47% and 0.61%, respectively, and showed a statistically significant difference. One hundred four patients (19%) underwent endometrial tissue sampling, including 22 patients who underwent hysterectomy (4%) and 82 patients who underwent endometrial biopsy (15%). Overall, 1 patient (2%) had significant endometrial pathology, namely, complex endometrial hyperplasia without atypia. CONCLUSIONS: A significant increase in the incidence of EM >or= 40 was observed with the implementation of TBS 2001. However, there was no difference in the proportion of patients that underwent endometrial tissue sampling. In addition, the incidence of clinically significant endometrial lesions associated with such a diagnosis was very low. The authors recommend that women with benign endometrial cells on Pap tests in women age 40 years or older should undergo endometrial biopsy only when additional clinical indicators are identified.