Editorial: Optimizing Schools of Cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

Optimizing schools of cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

Current State of Cytologic-Histologic Correlation Implementation for North American and International Laboratories: Results of the College of American Pathologists Cytopathology Committee Laboratory Practices in Gynecologic Cytology Survey.

CONTEXT.­: The College of American Pathologists (CAP) updated the Laboratory Accreditation Program Cytopathology Checklist to assist laboratories in meeting and exceeding the Clinical Laboratory Improvement Amendments standards for gynecologic cytologic-histologic correlation (CHC). OBJECTIVE.­: To survey the current CHC practices. DESIGN.­: Data were analyzed from a survey developed by the committee and distributed to participants in the CAP Gynecologic Cytopathology PAP Education Program mailing. RESULTS.­: Worldwide, CHC practice is nearly universally adopted, with an overall rate of 87.0% (568 of 653). CHC material was highly accessible. CHC was commonly performed real time/concurrently at the time the corresponding surgical pathology was reviewed. Investigation of CHC discordances varied with North American laboratories usually having a single pathologist review all discrepant histology and cytology slides to determine the reason for discordance, while international laboratories have a second pathologist review histology slides to determine the reason for discordance. The cause of CHC discordance was primarily sampling issues. The more common statistical metrics for CHC monitoring were the total percentage of cases that correlated with subsequent biopsies, screening error rate by cytotechnologist, and interpretative error rate by cytotechnologist. CONCLUSIONS.­: Many laboratories have adopted and implemented the CHC guidelines with identifiable differences in practices between North American and international laboratories. We identify the commonalities and differences between North American and international institutional practices including where CHC is performed, how CHC cases are identified and their accessibility, when CHC is performed, who investigates discordances, what discordances are identified, and how the findings affect quality improvement.

Rescreening Practices of Negative Papanicolaou Tests With Positive Human Papillomavirus Test Result.

CONTEXT.­: The yield of the prospective rescreening process for "negative for intraepithelial lesion or malignancy" (NILM) Papanicolaou (Pap) tests is higher with the inclusion of a greater proportion of high-risk cases. One of the suggested criteria for classifying a Pap test finding as high risk is recent or concurrent high-risk human papillomavirus (HPV) positivity. OBJECTIVE.­: To evaluate how the results of HPV testing have been incorporated in the prospective rescreening of NILM Pap tests across a wide range of laboratories. DESIGN.­: A questionnaire survey was sent to laboratories participating in the 2019 College of American Pathologists (CAP) Gynecologic Cytology (PAP Education) Program. RESULTS.­: Of the 1507 participating laboratories, 667 (44%) responded to the survey. Most laboratories (59.4%; 396 of 667) had not incorporated HPV test/genotyping results to select NILM Pap tests for rescreening. Amongst the remaining laboratories, for NILM HPV-positive Pap test results, 112 (16.8%) had a policy to rescreen by a cytotechnologist only, 51 (7.6%) by a pathologist only, and 86 (12.9%) by both. Of 264 laboratories, 181 (68.6%) reported the cytology upon availability of the HPV test result and completion of the secondary review. Of 661 laboratories, 145 (21.9%) included consensus-type recommendations in the cytology report for such Pap tests. CONCLUSIONS.­: This CAP survey provides significant information regarding the current trends in the use of HPV test results in prospective rescreening of NILM Pap tests. Future studies on quality improvement can further assist in the standardization of this process across different laboratories.

Moving forward-the 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors and beyond: implications and suggestions for laboratories.

The 2019 ASCCP Risk Based Management Consensus Guidelines for prevention of cervical cancer promote clinical management recommendations aligned with our increased understanding of HPV biology and cervical carcinogenesis. They employ HPV-based testing as the basis for risk estimation, allow for personalized risk-based management by incorporating knowledge of current results with prior results, and streamline incorporation of new test methods as they are validated. They continue to support the principles of "equal management for equal risk" and "balancing harms and benefits" adopted in the 2012 version of the guidelines. These updated guidelines will be able to adjust for decreasing CIN3+ risks as more patients who received HPV vaccination reach screening age. Pathology organizations were closely involved in the development of these guidelines. Herein the pathologists who served as representatives to the 2019 ASCCP guidelines steering committee and workgroups, summarize the changes that are relevant to laboratories, pathologists, and cytotechnologists. Prior relevant screening and reporting recommendations that have not been widely and/or inconsistently adopted by laboratories are also discussed and considerations for modification of laboratory practices offered.

Performance Characteristics of Cerebrospinal Fluid Cytology: An Analysis of Responses From the College of American Pathologists Nongynecologic Cytopathology Education Program.

CONTEXT: - Cerebrospinal fluid cytology is a critical diagnostic tool for the diagnosis of many conditions affecting the central nervous system. OBJECTIVE: - To assess the performance characteristics of cerebrospinal fluid cytology samples by evaluating participant interpretations within the College of American Pathologists Nongynecologic Cytopathology Education program. DESIGN: - Participant interpretations (N = 46 264) evaluated in the College of American Pathologists Nongynecologic Cytopathology Education Program were examined for concordance with the general category and with the reference diagnosis. Two nonlinear mixed models were used to analyze the concordance rates. RESULTS: - The overall concordance rates for the general category and reference diagnosis were 92.1% and 81.0%, respectively. In the malignant category, the concordance rates with the reference diagnosis were lowest for diagnoses of nonhematopoietic small blue round cell tumors (54.8%) and metastatic malignancy (77.5%); the concordance rate with the reference diagnosis was highest for leukemia/lymphoma (94.0%). In the benign category, the concordance rate was lowest for normal cerebrospinal fluid reference diagnoses (58.6%), followed by acute and chronic inflammation (64.6%), fungal infection (80.8%), and macrophages (85.3%). Significant differences in concordance were uncovered when performance was evaluated by participant type and stain technique. Leukemia/lymphoma was the most common diagnosis for misclassified nonhematopoietic small blue round cell tumor cases and negative or inflammatory cerebrospinal fluid cases. CONCLUSIONS: - This study illustrates the difficulties in achieving accurate diagnoses from cerebrospinal fluid specimens, particularly for nonhematopoietic small blue round cell tumors and normal and inflammatory cerebrospinal fluid specimens.

Primary HPV cervical cancer screening in the United States: Are we ready?

In September 2017, the United States Preventive Services Task Force put forth updated draft guidelines for cervical cancer screening in the United States, which were then open to public comment. The recommendations allowed for every-3-year cervical cytology screening in women aged 21 to 65 years with an option for every-5-year high-risk human papillomavirus testing in women aged 30 to 65 years. There was no option for cotesting. Other recommendations were similar to those published by other professional organizations. The Cytopathology Education and Technology Consortium provided an official response during the open comment period, which is summarized here along with additional commentary by the authors.

False-Negative Interpretation of Adenocarcinoma In Situ in the College of American Pathologists Gynecologic PAP Education Program.

CONTEXT: - Adenocarcinoma in situ (AIS) is difficult to correctly interpret on Papanicolaou (Pap) cytology slides and false-negative interpretations of AIS can cause significant problems in daily practice. OBJECTIVE: - To investigate the false-negative interpretation rate of AIS and the factors related to false-negative interpretation through responses in an educational environment. DESIGN: - We retrospectively evaluated 11 337 responses in the PAP Education Program (PAP-Edu) from 173 AIS slides from 2011 to 2015. The false-negative interpretation rate, most common false-negative interpretations, and related other factors were evaluated. RESULTS: - The overall false-negative rate was 6.9% (784 of 11 337). Respondents correctly interpreted AIS 50.0% (5667 of 11 337) of the time; high-grade intraepithelial lesion (HSIL) and malignancies (adenocarcinoma, squamous cell carcinoma, and other carcinomas) accounted for 42.7% (4842 of 11 337) and low-grade intraepithelial lesion accounted for 0.4% (44 of 11 337) of responses. Overall, 92.7% (10 509 of 11 337) of responses were HSIL and above. Among 784 false-negative responses, negative for intraepithelial lesion or malignancy was the most common (61.5% [482 of 784]), followed by reparative changes (24.1% [189 of 784]) and atrophic vaginitis (7.7% [60 of 784]). Overall, pathologists' responses showed a significantly higher false-negative rate than cytotechnologists' responses (8.3%, 403 of 4835 versus 5.7%, 275 of 4816; P < .001). The false-negative response rates were not statistically different among preparation types. CONCLUSIONS: - The low correct interpretation rate and higher false-negative rate for AIS demonstrate the difficulty in interpreting AIS on Pap cytology, which may cause clinical consequences. The higher false-negative rate with pathologists than with cytotechnologists suggests cytotechnologists' higher screening sensitivity for AIS or cautious interpretation to avoid false-positive results by pathologists.

Update on the College of American Pathologists Experience With High-Risk Human Papillomavirus Proficiency Testing for Cytology.

CONTEXT: - Since 2008, the College of American Pathologists has provided the human papillomavirus for cytology laboratories (CHPV) proficiency testing program to help laboratories meet the requirements of the Clinical Laboratory Improvement Amendments of 1988. OBJECTIVES: - To provide an update on trends in proficiency testing performance in the College of American Pathologists CHPV program during the 4-year period from 2011 through 2014 and to compare those trends with the preceding first 3 years of the program. DESIGN: - Responses of laboratories participating in the CHPV program from 2011 through 2014 were analyzed using a nonlinear mixed model to compare different combinations of testing medium and platform. RESULTS: - In total, 818 laboratories participated in the CHPV program at least once during the 4 years, with participation increasing during the study period. Concordance of participant responses with the target result was more than 98% (38 280 of 38 892). Overall performance with all 3 testing media-ThinPrep (Hologic, Bedford, Massachusetts), SurePath (Becton, Dickinson and Company, Franklin Lakes, New Jersey), or Digene (Qiagen, Valencia, California)-was equivalent (P = .51), and all 4 US Food and Drug Administration (FDA)-approved platforms-Hybrid Capture 2 (Qiagen), Cervista (Hologic), Aptima (Hologic), and cobas (Roche Molecular Systems, Pleasanton, California)-outperformed laboratory-developed tests, unspecified commercial kits, and other (noncommercial) methods in ThinPrep medium (P < .001). However, certain off-label combinations of platform and medium, most notably Cervista with SurePath, demonstrated suboptimal performance (P < .001). CONCLUSIONS: - Laboratories demonstrated proficiency in using various combinations of testing media and platforms offered in the CHPV program, with statistically significant performance differences in certain combinations. These observations may be relevant in the current discussions about FDA oversight of laboratory-developed tests.

Human Papillomavirus Genotyping Testing Practice in 2014: Results of a College of American Pathologists National Survey.

CONTEXT: - College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratories. OBJECTIVE: - To investigate human papillomavirus (HPV) genotyping testing practice patterns in laboratories in 2014. DESIGN: - Data were analyzed from the CAP HPV Genotyping Practices Supplemental Questionnaire distributed to 749 laboratories participating in the CAP Human Papillomavirus (High Risk) for Cytology Program. RESULTS: - Six hundred four of 749 laboratories (80.6%) responded to the survey. More laboratories offered HPV genotyping testing and performed in-house HPV genotyping testing as compared to previous surveys. The Roche cobas HPV test was the most commonly used genotyping method (37.0%; 160 of 433), followed by Hologic Aptima HPV16 18/45 (26.1%; 113 of 433) and Hologic Cervista HPV16/18 (14.3%; 62 of 433). Most laboratories (287 of 399; 71.9%) offered HPV genotyping for high-risk HPV cases regardless of Papanicolaou (Pap) test results and patient age; this pattern was more common in laboratories using cobas. The remaining laboratories specifically offered testing to women with a negative Pap test result at age 30 years and older (65.2%, 73 of 112) or all ages (37.5%, 42 of 112). The median reporting rates of HPV16 and/or HPV18 positivity were 20.6%, 25.7%, 21.1%, and 57.4% for women with positive high-risk HPV adjunctive negative Pap results, atypical squamous cells of undermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous lesion, respectively. CONCLUSIONS: - Human papillomavirus genotyping testing has increased. Roche cobas and Hologic Aptima genotype methods were the most common, and laboratories using cobas usually offered genotyping regardless of Pap test result and age. The data provide a baseline and trend of HPV genotyping test practices in 2014.

Misinterpretation Rates of High-Grade Squamous Intraepithelial Lesion in the College of American Pathologists Gynecologic PAP Education and PAP Proficiency Test Program.

Context .- Misinterpretation of high-grade squamous intraepithelial lesion (HSIL) is an important problem in daily practice and in the College of American Pathologists (CAP) PAP Proficiency Test (PAP-PT). Objective .- To investigate factors related to misinterpretation of HSIL through responses in a proficiency test versus an educational environment. Design .- We retrospectively evaluated 28 000 responses in the PAP Education Program (PAP-Edu) and 59 140 responses in PAP-PT from 1147 field-validated HSIL slides from 2007 to 2014. The related factors, such as program types, preparation types, participant types, and program years, were evaluated. Results .- Overall, 4.0% (2379 of 59 140) of responses for HSIL slides from PAP-PT were misinterpreted as either low-grade squamous intraepithelial lesion (LSIL) or negative, significantly more than those from PAP-Edu (3.2%; 898 of 28 000). However, the false-negative rate (misinterpreted as negative) was 0.9% (519 of 59 140) for PAP-PT, lower than that for PAP-Edu (1.0%; 266 of 28 000). The misinterpretation rates in PAP-PT trended down with time. Misinterpretation rates did not vary significantly by preparation methods. The misinterpretation rate for HSIL in the pathologists' responses was lower than that in cytotechnologists' in PAP-PT. More HSIL was misinterpreted as LSIL than as benign in both programs. Cytotechnologists interpreted HSIL as LSIL twice as much as pathologists. The most common false-negative misinterpretations were negative for intraepithelial lesion or malignancy and reparative change. Conclusions .- The higher LSIL misinterpretation rate by cytotechnologists may be related to the differences in reporting responsibilities and proficiency test grading criteria. The trend of gradually decreasing misinterpretation rates of a reference diagnosis of HSIL in the PAP-PT program may be related to higher test-taking confidence and better preparation through educational programs. The fact that pathologists performed better than cytotechnologists in PAP-PT, but not in PAP-Edu, may reflect a heightened approach and attentiveness in the test-taking environment for pathologists.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk HPV (hrHPV) testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology and cotesting (cytology in combination with hrHPV testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for healthcare providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Use of the NBME Comprehensive Basic Science Examination as a progress test in the preclerkship curriculum of a new medical school.

In the present study, we describe the innovative use of the National Board of Medical Examiners (NBME) Comprehensive Basic Science Examination (CBSE) as a progress test during the preclerkship medical curriculum. The main aim of this study was to provide external validation of internally developed multiple-choice assessments in a new medical school. The CBSE is a practice exam for the United States Medical Licensing Examination (USMLE) Step 1 and is purchased directly from the NBME. We administered the CBSE five times during the first 2 yr of medical school. Student scores were compared with scores on newly created internal summative exams and to the USMLE Step 1. Significant correlations were observed between almost all our internal exams and CBSE scores over time as well as with USMLE Step 1 scores. The strength of correlations of internal exams to the CBSE and USMLE Step 1 broadly increased over time during the curriculum. Student scores on courses that have strong emphasis on physiology and pathophysiology correlated particularly well with USMLE Step 1 scores. Student progress, as measured by the CBSE, was found to be linear across time, and test performance fell behind the anticipated level by the end of the formal curriculum. These findings are discussed with respect to student learning behaviors. In conclusion, the CBSE was found to have good utility as a progress test and provided external validation of our new internally developed multiple-choice assessments. The data also provide performance benchmarks both for our future students to formatively assess their own progress and for other medical schools to compare learning progression patterns in different curricular models.

The role of monitoring interpretive rates, concordance between cytotechnologist and pathologist interpretations before sign-out, and turnaround time in gynecologic cytology quality assurance: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 1.

CONTEXT: The College of American Pathologists (CAP) conducted a national survey of gynecologic cytology quality assurance (QA) practices. Experts in gynecologic cytology were asked to join 5 working groups that studied the survey data on different aspects of QA. Evaluating the survey data and follow-up questions online, together with a review of pertinent literature, the working groups developed a series of preliminary statements on good laboratory practices in cytology QA. These were presented at a consensus conference and electronic voting occurred. OBJECTIVE: To evaluate a set of QA monitors in gynecologic cytology. Working group 1 evaluated (1) monitoring interpretive rate categories for Papanicolaou tests (Pap tests), (2) concordance of cytotechnologist and pathologist interpretations before sign-out, and (3) turnaround time for Pap tests. DATA SOURCES: The statements are based on a survey of gynecologic cytology QA practice patterns and of opinions from working group members and consensus conference attendees. CONCLUSIONS: The outcomes of this process demonstrate the current state of practice patterns in gynecologic cytology QA. Monitoring interpretive rates for all Bethesda System categories is potentially useful, and it is most useful to monitor interpretive rates for cytotechnologists individually and in comparison to the entire laboratory. Laboratories need to determine what level of discrepancy between cytotechnologist and pathologist interpretations of Pap tests is important to track. Laboratories should consider formalizing procedures and policies to adjudicate such discrepant interpretations. Turnaround time should be monitored in gynecologic cytology, but individual laboratories should determine how to measure and use turnaround time internally.