Diane D. Davey

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.

Quality management in gynecologic cytology using interlaboratory Comparison

OBJECTIVEnTo describe a comprehensive integrated laboratory quality management plan for gynecologic cytology.nnnDESIGN AND SETTINGnCytopathology laboratory performance monitors with interlaboratory comparison.nnnRESULTSnUtilizing College of American Pathologists Q-Probes studies, the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, and other published data, a quality management program for gynecologic cytology involving diagnostic statistics, screening limits and competency assessment, retrospective rescreening, real-time rescreening, cytology-biopsy correlation, follow-up of patients with abnormal cytology results, turnaround time, examination of unknown slides (survey programs), and new technology is described.nnnCONCLUSIONnRegular coordinated monitoring of performance, with longitudinal and interlaboratory comparison utilizing the methods described, provides an opportunity to optimize gynecologic cytology service.

Cervical cytology specimen adequacy: Patient management guidelines and optimizing specimen collection

Objective. To provide updated management guidelines according to cervical cytology specimen adequacy and techniques to optimize adequacy based on literature review and expert opinion. Materials and Methods. Selected members of the American Society for Colposcopy and Cervical Pathology committee and invited experts conducted a literature review and discussed appropriate management and areas for future research emphasis. Results. The guidelines recommend a repeat Pap test in a short interval of 2 to 4 months for most women when the cytology result is unsatisfactory. The preferred follow-up for women with a negative cytology result lacking an endocervical/transformation zone component or showing other quality indicators is a repeat Pap test in 12 months. Indications for an early repeat Pap test in 6 months are provided, and the influence of human papillomavirus testing results on management is discussed. Techniques for optimizing specimen adequacy are provided in detail. Conclusion. The specimen adequacy management guidelines will help promote uniform and optimal follow-up of patients receiving cervical cytology screening. The topics for future research emphasis will be helpful in promoting studies in needed areas.

Endometrial Cells in Cervical Cytology: Review of Cytological Features and Clinical Assessment

Abstract: The 2001 Bethesda System for Reporting Cervical Cytology recommends reporting benign exfoliated endometrial cells in women age 40 and older, and a review of the literature supports this recommendation. Stromal cells and histiocytes do not need to be reported. The effect of hormonal therapy on endometrial shedding is reviewed. Clinical information should be provided to the laboratory so that appropriate educational notes can be appended to the cytology report. Benign endometrial cells in premenopausal women in the first half of the cycle are not associated with significant pathology and such women do not need additional evaluation. Significant pathology is also unlikely in the second half of the cycle and evaluation may not be required unless clinically indicated. Initial evaluation of other women with benign endometrial cells may include either endometrial sampling or transvaginal ultrasound. Atypical endometrial cells are associated with a higher rate of significant pathology and should lead to additional evaluation. Additional prospective studies on the management of patients with endometrial cells on Pap tests are needed.

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

Abstract 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.

Reparative Changes and the False-Positive/False-Negative Papanicolaou Test A Study From the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology

CONTEXTnReparative changes can be a diagnostic challenge on Papanicolaou tests and must be distinguished from epithelial cell abnormalities. Both squamous intraepithelial lesions (SIL) and carcinoma may be underdiagnosed as repair. This study examines laboratory and cytologist performance in the diagnosis of repair.nnnOBJECTIVESnTo determine if laboratories and cytologists can consistently distinguish reparative changes from SIL and carcinoma and to document how often SIL and carcinoma are mistaken for repair in a standardized educational slide program.nnnDESIGNnResults for reparative changes, SIL, and carcinoma slides from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology for 1998 were analyzed. Only results from validated referenced slide responses were used.nnnRESULTSnThe concordancy rate for reparative-change slides, that is, any response of within normal limits or benign cellular changes, ranged from 91% to 94% for cytotechnologist, pathologist, and laboratory responses. False-negative rates for squamous carcinoma and adenocarcinoma, high-grade SIL, and low-grade SIL ranged from 0.47% to 5.41%; the proportion of false-negative diagnoses of reparative changes ranged from 24% to 62% of all discordant responses.nnnCONCLUSIONSnOf all benign cellular changes and within normal limits categories in the Interlaboratory Comparison Program in Cervicovaginal Cytology, repair most often elicits a false-positive laboratory response. Underdiagnosing epithelial abnormalities as repair is also a source of false-negative Papanicolaou test results.

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.

Accuracy of ThinPrep Imaging System in detecting low-grade squamous intraepithelial lesions.

CONTEXTnThe ThinPrep Imaging System (Imager) for cervical cytology is used in many US laboratories, but the ability of the system to identify classic changes of low-grade squamous intraepithelial lesion (LSIL) has not been independently reported.nnnOBJECTIVEnTo evaluate the accuracy of this system in detecting classic LSIL cells.nnnDESIGNnA total of 114 imaged ThinPrep LSIL cases from April to June 2005 were reviewed to determine whether the most diagnostically relevant cells were present in the 22 fields selected by Imager. Those LSIL specimens from January to June 2005 that were initially screened by the Imager and classified as negative in the 22 fields were also reviewed. The average number of classic koilocytes per slide was compared among cases that had koilocytes within 22 fields with cases upgraded during full review.nnnRESULTSnTwelve (10.5%) of 114 LSIL cases from April to June 2005 did not show diagnostic LSIL cells within the initial 22 fields. Full manual rescreening was performed on 1025 cases from January to June (20.4% of negative cases). Nine cases that were initially negative in the 22 fields were revised to LSIL (2.4% of all 381 LSIL cases reported from January to June 2005). An average of 10 to 11 koilocytes were present in these 2 groups, which was significantly lower than the average of 75 koilocytes in cases in which the 22 Imager-selected fields showed LSIL.nnnCONCLUSIONSnAlthough the ThinPrep Imager finds abnormal cells in most LSIL cases, the system may have limitations in detecting koilocytes in the 22 Imager-selected fields. When 10% quality control rescreening is performed as required by federal regulations, full manual rescreening will provide the most accurate results.

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

CONTEXTnThe 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.nnnOBJECTIVEnTo 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.nnnDATA SOURCESnThe statements are based on a survey of gynecologic cytology QA practice patterns and of opinions from working group members and consensus conference attendees.nnnCONCLUSIONSnThe 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.

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.