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.

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 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.

2013 statement on human papillomavirus [corrected] test utilization.

This statement from the Cytopathology Education and Technology Consortium summarizes appropriate and inappropriate uses of human papillomavirus testing in cervical cancer screening based on guidelines from the American Society for Colposcopy and Cervical Pathology and the American Cancer Society. © 2014 S. Karger AG, Basel.

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.

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.

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.

Performance of specific morphologic features in distinguishing low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions in borderline cases: a College of American Pathologists Cytopathology Committee multiobserver study.

INTRODUCTION: Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program. MATERIALS AND METHODS: Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL). We evaluated the significance of these 11 variables using a nonlinear mixed model analysis. RESULTS: LSIL had greater concordance (92 of 121 responses; 76.0% concordance) than HSIL (68 of 110 responses; 61.8% concordance; P < 0.001). The only predictors of misclassified cases were the number of atypical squamous metaplastic cells and the number of HSIL cells (P < 0.001). The more of these cells identified, the more likely the reviewers were to classify the slide as HSIL. The reproducibility of the diagnosis was fair (Gwet's agreement coefficient, 0.33). CONCLUSIONS: Interobserver reproducibility is a challenge for a subset of cases with features intermediate between LSIL and HSIL. Atypical squamous metaplasia and dysplastic nuclei with a nuclear/cytoplasmic ratio greater than one half of the cell volume (HSIL) present on a Pap test influenced the likelihood that a reviewer would interpret the case as HSIL rather than LSIL.

Impact of laboratory work-up of lymphoma guidelines on cytopathology practices.

A multi-society expert panel recently published evidence-based guidelines and recommendations for the primary diagnosis and classification of lymphoma, which included a public comment period. The guideline concludes: "primary diagnosis and classification of lymphoma can be achieved with a variety of specimens." The guideline recommends that fine-needle aspiration biopsy (FNAB) cytomorphology not be used without ancillary testing, and that either flow cytometry or immunohistochemical immunophenotyping be performed for any type of specimen. Either excisional or core biopsy should be obtained when there is a high suspicion of lymphoma, and excision is recommended when feasible for Hodgkin lymphoma primary diagnosis. The use of cerebrospinal fluid to diagnose central nervous system lymphoma is discussed. For any patient with initial negative biopsy or fluid specimens and a high suspicion of lymphoma, additional tissue samples should be obtained. Additional molecular testing and good practice statements are summarized in the guideline. Cytopathologists should continue to advocate for judicious use of lymph node FNAB as an excellent triage tool that may require additional tissue biopsy for definitive diagnosis.

Co-design and development of online video resources about immunotherapy with patients and their family.

BACKGROUND: Patients receiving novel treatments like immune checkpoint inhibitor therapy (ICI or immunotherapy) to treat their cancer require comprehensive information so they know what to expect and to encourage the identification and reporting of possible side-effects. Videos using patient stories can be reassuring and an effective method for conveying health information. OBJECTIVE: The objective of this study was to use a co-design process to develop video resources about immunotherapy to identify a) the key informational and supportive care needs of patients and family carers and b) topics clinicians recommended be addressed during pre-treatment nurse-led education. PATIENT INVOLVEMENT: Experience Based Co-design (EBCD) provided the framework for video development, to facilitate patient and carer involvement in every stage of research design and implementation, and video design and development. METHODS: Data were collected and used in four stages: 1) qualitative interviews, 2) co-design workshop, 3) filming plan and 4) feedback and editing. RESULTS: Thirty-five individuals contributed to the development of a suite of five videos called "Immunotherapy: What to Expect". Videos covered general treatment information, preparation for infusion, potential side-effects, balancing lifestyle with treatment and seeking support. Video run time ranges from 6 to 15 min. DISCUSSION: The EBCD process ensured that videos were developed to meet patient and carer identified needs associated with commencing and managing ICI therapy. The structure of EBCD in facilitating patient and carer involvement throughout the research and video development process ensured transparency throughout the project, and continuity of message, scope and outcomes. PRACTICAL VALUE: EBCD is a useful framework for developing patient-centred health resources. The videos developed are now available for patients and carers via YouTube, and provide education and support tailored to this groups' needs regarding ICI therapy for cancer.

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: review of ancillary testing modalities and implications for follow-up.

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

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.

The Differential Diagnosis of Reparative Changes and Malignancy: Performance in the College of American Pathologists Pap Education and Proficiency Testing Programs.

CONTEXT.­: Repair is a challenging diagnosis and a significant source of false-positive (FP) interpretations in cervical cytology. No large-scale study of performance of repair in the liquid-based era has been performed. OBJECTIVE.­: To evaluate the performance of repair in the College of American Pathologists Pap Education and Proficiency Testing (PT) programs. DESIGN.­: The FP rate for slides classified as repair was evaluated by preparation type, participant type (cytotechnologist, pathologist, or laboratory), and program. The specific misdiagnosis category and individual slide performance were also evaluated. The rate of misclassification of slides as repair by participants for other diagnostic categories in the Pap Education program was assessed. RESULTS.­: The overall FP rate was 1700 of 12 715 (13.4%). There was no significant difference by program or preparation type. Within the Education program there was no difference by participant type, but pathologists' FP rate in the PT program (47 of 514, 9.1%) was significantly better than cytotechnologists in the PT program (51 of 380, 13.4%) and pathologists in the Education program (690 of 4900, 14.1%). High-grade squamous intraepithelial lesions/cancers (HSIL+) accounted for 1380 of 1602 FP interpretations (86%) in Education, but 43 of 98 (43.9%) in PT. Most slides had a low rate of misclassification, but a small number were poor performers. False-negative diagnosis of HSIL+ as repair was less common, ranging from 0.7% to 1.8%. CONCLUSIONS.­: Despite initial indications that liquid-based cytology might reduce the rate of misclassification of repair, FP interpretations remain common and are no different by preparation type. Misclassification is most commonly as HSIL or carcinoma, potentially resulting in significant patient harm.

Bethesda 2014 Implementation and Human Papillomavirus Primary Screening: Practices of Laboratories Participating in the College of American Pathologists PAP Education Program.

CONTEXT.­: Cervical cancer screening laboratory practices may evolve with new terminology and technologies. OBJECTIVE.­: To investigate changes in cervical cytopathology practice resulting from the 2014 Bethesda System updates and screening technologies. DESIGN.­: Questionnaires accompanied 2016 and 2017 mailings of the College of American Pathologists PAP Education program. RESULTS.­: In 2016, most laboratories surveyed had adopted or were planning to adopt 2014 Bethesda System updates, and the majority (53%; 365 of 689) used an age cutoff of 45 for reporting benign-appearing endometrial cells. However, 51.3% (354 of 690) of laboratories used the term low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion, for cases with indeterminate features, and 44.9% (298 of 664) of laboratories used a 5000-cell cutoff for minimum squamous cellularity for posthysterectomy and posttherapy specimens. Reporting rates for cervical cytology metrics changed very little from 2013 to 2016, and the median ratio of atypical squamous cells to squamous intraepithelial lesion cases was 1.9 for ThinPrep and 1.8 for SurePath preparations. Most laboratories (59.4%; 389 of 655) did not offer stand-alone primary human papillomavirus (HPV) testing in 2017, and primary HPV testing accounted for a low proportion of HPV testing volumes. The Roche Cobas method was the most common platform for HPV primary screening. CONCLUSIONS.­: These questionnaire surveys provide data about the current status of cervical cytology screening, including changes related to the 2014 Bethesda System updates and the adoption of HPV primary screening techniques.

Trends in Thyroid Fine-Needle Aspiration Cytology Practices: Results From a College of American Pathologists 2016 Practice Survey.

CONTEXT.­: The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2016 survey concerning thyroid fine-needle aspiration (FNA). OBJECTIVE.­: To provide a cross-sectional survey of thyroid cytology practices in 2016. DESIGN.­: In 2016, a survey was sent to 2013 laboratories participating in the College of American Pathologists Non-Gynecologic Cytology Education Program (NGC-A) requesting data from 2015-2016 on several topics relating to thyroid FNA. RESULTS.­: A total of 878 laboratories (43.6% of 2013) replied to the survey. Radiologists performed the most thyroid FNA procedures in most laboratories (70%; 529 of 756), followed by endocrinologists (18.7%; 141 of 756), and most of these were performed under ultrasound guidance (92.1%; 699 of 759). A total of 32.6% of respondents (251 of 769) provided feedback on unsatisfactory rates for nonpathology providers who performed FNA. Intraprocedural adequacy assessment was primarily performed by attending pathologists (77.4%; 490 of 633) or cytotechnologists (28.4%; 180 of 633). Most laboratories used the Bethesda System for Reporting Thyroid Cytopathology (89.8%; 701 of 781) and performed molecular testing based on clinician request (68.1%; 184 of 270) rather than FNA diagnosis. Correlation of thyroid excisions with prior cytology results most often occurred retrospectively (38.4%; 283 of 737) and was used for pathologist interpretive quality assurance purposes. CONCLUSIONS.­: These survey results offer a snapshot of national thyroid FNA cytology practices in 2016 and indicate that standardized cytology terminology is commonly used; pathologists perform most immediate adequacy assessments for thyroid FNA; laboratories use correlation statistics to evaluate pathologists' performance; and molecular tests are increasingly requested for indeterminate interpretations, but reflex molecular testing is rare.

Low-Grade Squamous Intraepithelial Lesion or High-Grade Squamous Intraepithelial Lesion? Concordance Between the Interpretation of Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion in Papanicolaou Tests: Results From the College of American Pathologists PAP Education Program.

CONTEXT.­: Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. OBJECTIVE.­: To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. DESIGN.­: We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. RESULTS.­: There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL ( P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). CONCLUSIONS.­: More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.