Mucinous Neoplasms of the Ovary: Radiologic-Pathologic Correlation.

Mucinous neoplasms of the ovary account for 10%-15% of ovarian neoplasms. They may be benign, borderline, or malignant. The large majority are benign or borderline, accounting for 80% and 16%-17%, respectively. Mucinous neoplasms of the ovary most commonly affect women in their 20s to 40s. The clinical manifestation is nonspecific, but most mucinous ovarian neoplasms manifest as large unilateral pelvic masses. At gross pathologic analysis, mucinous ovarian neoplasms appear as large multiloculated cystic masses. The contents of the cyst loculi vary on the basis of differences in internal mucin content. At histologic analysis, mucinous ovarian neoplasms are composed of multiple cysts lined by mucinous epithelium, often resembling gastrointestinal-type epithelium. Imaging evaluation most commonly includes US and/or MRI. The imaging findings parallel the gross pathologic features and include a large, unilateral, multiloculated cystic mass. The cyst loculi vary in echogenicity, attenuation, and signal intensity depending on the mucin content. Mucinous neoplasms of the ovary are staged surgically using the FIGO (International Federation of Gynecology and Obstetrics) staging system. Primary treatment is surgical, with adjuvant chemotherapy considered in the uncommon case of mucinous carcinoma with extraovarian disease. Since most mucinous ovarian neoplasms are benign or borderline, the overall prognosis is excellent.

Relative Effects of Age, Race, and Stage on Mortality in Gestational Choriocarcinoma.

OBJECTIVE: Gestational choriocarcinoma is a malignant form of gestational trophoblastic disease that usually arises after a molar pregnancy, but may follow any antecedent pregnancy. Investigations in this rare cancer are limited. We evaluated the prognostic effects of age, race, and stage in choriocarcinomas diagnosed for 4 decades. METHODS: Patients diagnosed as having gestational choriocarcinoma between 1973 and 2014 from the Surveillance, Epidemiology, and End Results program were eligible. Relationships with overall survival and cancer-specific survival were evaluated using log-rank testing and Cox modeling. Multivariate analyses included adjustments for age, race, and stage. RESULTS: There were 947 patients with choriocarcinoma including 403 non-Hispanic white (NHW) patients, 473 with distant stage, and 142 who died. Median age at diagnosis was 25 years for non-Hispanic black (NHB) patients and 35 years for Asian/Pacific Islanders (API) compared with 29 years for NHW patients (P = 0.0001). Five-year overall survival varied between 82% and 92% when diagnosed at the age of at least 40 years compared with less than 20 years (P < 0.0001), and from 85% to 95% in patients with distant vs local disease (P < 0.0001), respectively. Multivariate analysis demonstrated that age, race, and stage were independent predictors of mortality. Risk of death increased incrementally in patients diagnosed at 20 to 39 years of age (adjusted hazard ratio [aHR], 3.87; 95% confidence interval [CI], 1.69-8.86; P = 0.001) and at least 40 years of age (aHR, 7.18; 95% CI, 2.95-17.49; P < 0.0001) compared with 20 years or younger. Non-Hispanic black patients were the only racial group at higher risk of death compared with NHW patients (aHR, 1.86; 95% CI, 1.22-2.82; P < 0.004). Distant vs local disease added an additional risk of death (aHR, 2.43; 95% CI, 1.57-3.75; P < 0.0001) over that attributable to age at diagnosis and NHB race. Similar relationships to cancer-specific survival were also observed (P < 0.05). CONCLUSIONS: Most patients with choriocarcinoma have excellent prognosis. However, NHB patients and patients who are diagnosed at the age of at least 20 years or have distant stage have significantly worse mortality.

Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities.

We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.

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.

Cytologic-Histologic Correlation Practices for Nongynecologic Cytology Specimens: A Survey by the College of American Pathologists Cytopathology Committee.

CONTEXT.­: Cytologic-histologic correlation (CHC) is a Clinical Laboratory Improvement Amendments-mandated requirement for gynecologic cytology, but no similar requirement exists for nongynecologic cytology. This study presents the findings from a College of American Pathologists' survey of nongynecologic cytology practice patterns. OBJECTIVE.­: To survey the current CHC practices for nongynecologic cytology. DESIGN.­: Data were analyzed from a survey developed by the committee and distributed to participants in the Nongynecologic Cytopathology Education Program mailing. RESULTS.­: Adoption of CHC for nongynecologic cytology cases is worldwide, with 88.5% of institutions performing CHC on these specimens, a substantial increase from previous years. Performance of CHC varied by institution type, with clinic or regional/local independent laboratories and national/corporate laboratories performing CHC significantly less frequently than hospitals, university hospitals/academic medical centers, and Veterans Administration/Department of Defense hospital institutions. Most CHC was performed concurrently in real time, when the corresponding surgical specimen was reviewed. Selection for real-time concurrent CHC was by the interpreting pathologist, the pathologist diagnosing the surgical biopsy sample or cytopathology case, or both. Sampling was by far the most common reason for discordance. A 2-step difference was the most frequent threshold for discordance between cytology and surgical specimens, but this criterion varied among institutions, with no majority definition. The positive predictive value of a positive cytology finding was calculated rarely in North American institutions but was calculated more frequently in international institutions. CONCLUSIONS.­: CHC practices for nongynecologic cytopathology mirror those found for CHC of gynecologic cytopathology.

Intravascular Large B-Cell Lymphoma.

CONTEXT.­: Intravascular large B-cell lymphoma (IVLBCL) is a rare hematopathologic entity, posing both a clinical and histologic challenge for diagnosis. Numerous pitfalls can hinder making the diagnosis. OBJECTIVE.­: To summarize recent developments in literature pertaining to IVLBCL and point out key pitfalls pathologists should be prepared to encounter. DATA SOURCES.­: Literature review via PubMed search and hospital (Darnall Medical Library) resources. CONCLUSIONS.­: The 3 primary pitfalls of IVLBCL include masking of IVLBCL, mimicry by IVLBCL, and mimicry of IVLBCL. These scenarios illustrate the importance of histologic pattern recognition and subsequent usage of immunohistochemistry, especially in context of a clinical history that may be noncharacteristic.

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.

The international system for reporting serous fluid cytopathology-diagnostic categories and clinical management.

INTRODUCTION: Effusions can develop inside serous cavities in several pathologic states, both neoplastic and non-neoplastic. They are easy to drain and can provide useful diagnostic information. However, the reported diagnostic efficacy of these specimens has not been uniform across different laboratories. To standardize practices, the international system for reporting serous fluid cytology (TIS) was developed in accordance with the best international practices, the most up-to-date reported data, and expert consensus. RESULTS: TIS has set the basic principles for laboratory handling of serous effusion specimens, defined the adequacy criteria, and set a standardized reporting terminology with well-defined criteria for each diagnostic category. These include nondiagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, and malignant. Each can provide useful inherent information for appropriate clinical management and follow-up, with a defined expected diagnostic category incidence and risk of malignancy. CONCLUSIONS: TIS applies to serous fluids collected from the pleura, peritoneal, and pericardial cavities. Using TIS, indeterminate categories are presented as either preliminary or as options of last resource. TIS has emphasized the role of ancillary tests in arriving at the correct interpretation within each category. It also has emphasized the importance of a malignant diagnosis as a definitive diagnosis, comparable to histologic examinations. Because of the well-documented outcomes in the adoption of uniform cytology terminology for other organ systems, we recommend the use of the upcoming TIS and believe its use will be paramount to improving the diagnostic yield in this area of cytology.

Proceedings of the American Society of Cytopathology Companion Session at the 2019 United States and Canadian Academy of Pathology Meeting Part 1: towards an International System for Reporting Serous Fluid Cytopathology.

INTRODUCTION: The International System for the Reporting of Serous Fluid Cytopathology was initiated to provide a common language for cytopathology reports on body fluids. MATERIALS AND METHODS: The International Academy of Cytology and the American Society of Cytopathology collaborated to provide evidence-based and expert-driven terminology for reporting serous fluids. Lead editors were selected and expert authors invited to form working groups for the diagnostic categories and special sections. RESULTS: Preliminary results of the collaboration include the 6 diagnostic terminology categories: non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, malignant-primary, and malignant-metastatic. Four special sections on ancillary testing, peritoneal washings, cytotechnical aspects, and quality assurance will appear in the final text. Initial results of an international survey indicate strong support for a uniform terminology for reporting serous fluids. CONCLUSIONS: This article outlines the initial findings of the collaboration as presented to the United States and Canadian Academy of Pathology at the 2019 annual meeting at the National Harbor, MD.

Touch imprint (TI) cytology of needle core biopsies (NCB) in pathology laboratories: A practice survey of participants in the College of American Pathologists (CAP) Non Gynecologic Cytopathology (NGC) Education Program.

BACKGROUND: Intra-procedural assessment of touch imprint (TI) cytology from needle core biopsies (NCB) is used to ensure sample adequacy and to provide immediate diagnosis in various settings. We aimed to survey laboratories for current practices on the use of cytology with NCB. METHODS: A voluntary supplemental questionnaire including questions on demographics, personnel involved, sites, accessioning, and reporting was sent with the College of American Pathologists (CAP) 2015 Non gynecologic Cytopathology Education Program to survey practices of cytologic assessment of NCB. RESULTS: Among 844 respondents, 403 (48%) performed cytologic assessment of NCB. Common body sites included lung (94%; 368/392), liver (87%; 340/ 392), and lymph nodes/spleen (77%; 303/392). Most of the time, a pathologist was present on-site 75% (295/393) for adequacy assessment which was usually verbally reported to the provider performing the procedure. Specimens were prepared by cytotechnologists (50%; 193 of 388) or pathologists (45%; 176 of 388) by touching the core to the slide (50%; 196 of 390) and rolling the core on the slide (45%; 177/390). Among the respondents, 19% said that cytotechnologists independently performed immediate assessment of TI of NCB. Most laboratories (69%; 264/384) evaluated air-dried slides with a modified Giemsa stain and rendered one TI/NCB combined report (87%, 334/385). CONCLUSIONS: This is the first survey performed specifically to determine the practice of adequacy assessment of TI of NCB. Cytotechnologists are generally not performing adequacy assessment of TI without pathologist oversight. A single report is usually issued which includes the adequacy assessment as a part of the final report.

Self-collected Papanicolaou tests in the United States market: more questions than answers.

The United States Food and Drug Administration held a public hearing in January 2018 to consider how it should evaluate a self-collection device for cervical cytology. Although no such device has been approved for use in the US market, the implications for patients and cytologists could be both sweeping and complex. Herein, the existing literature basis for self-collected Papanicolaou testing is reviewed, and some questions raised by this testing are considered. Questions include: what would be the value to patients; how effective could self-collected Papanicolaou tests be; how might ordering and collection work; what are the unique pre-analytic, analytic, and post-analytic challenges of self-collected Papanicolaou testing; and what effect might self-collection have on cervical cancer rates?

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.

Internet-based gynecologic telecytology with remote automated image selection: results of a first-phase developmental trial.

A retrospective set of 191 gynecologic cytology slides with reference interpretations was run on an automated screening device that selects fields of view (FOVs) based on a hierarchical probability of abnormality being present. An interface was developed between the device and a remote server using customized image review software. FOVs were reviewed by 3 cytotechnologists and 3 cytopathologists, and binary triage (unsatisfactory for evaluation/negative for intraepithelial lesion or malignancy [NILM] vs "abnormal" [neither unsatisfactory nor NILM]) and specific interpretations were done. No morphologic training before FOV review was provided. Three or more reviewers agreed on the correct categorization of NILM/unsatisfactory in 89% (85/96) and abnormal in 83% (79/95). Three or more reviewers triaged cases to abnormal as follows: atypical squamous cells of uncertain significance, 83% (5/6); atypical squamous cells, cannot exclude high-grade lesion, 100% (3/3); low-grade squamous intraepithelial lesion (SIL), 83% (52/63); high-grade SIL, 94% (17/18); and atypical glandular cells, 40% (2/5). This procedure may have comparable sensitivity and specificity and possibly could provide effective initial triage to further evaluation. A review of individual cases suggests that further accuracy can be achieved with additional training and experience.

Cytologic-histologic correlation: Where are we now, and where are we going?

The author was the chair of a College of American Pathologists working group at the Gynecologic Cytopathology Quality Consensus Conference outlining then current practices in cytology-histology correlation, and published this work in the Archives of Pathology and Laboratory Medicine. Cancer Cytopathol 2018;126:301-8. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Performance Characteristics of Body Fluid Cytology Analysis of 344 380 Responses From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: - Body fluid cytology is an important diagnostic tool used to identify various conditions. However, an accurate diagnosis in this setting can sometimes be challenging. OBJECTIVE: - To identify the performance characteristics of body fluid cytology by analyzing participant responses from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. DESIGN: - Participant responses from 5102 slides were analyzed for concordance to the general category (GC) and to the reference diagnosis (RD). Nonlinear mixed models were used to analyze concordance. RESULTS: - The overall GC concordance was 95.2%. The GC type, participant type, and preparation type were significantly associated with GC concordance ( P < .001). Concordance for malignant cases was higher than it was for benign cases. Cytotechnologists had better GC concordance compared to pathologists. ThinPrep (Hologic, Marlborough, Massachusetts) slides had the highest GC concordance. Participant type, fluid type, preparation type, and participant interpretation were significantly associated with RD concordance ( P < .001). Pathologists performed better than cytotechnologists did for RD concordance. Pericardial fluid had the lowest RD concordance, especially for cases with normal or reactive findings. Modified Giemsa-stained slides performed best for lymphoma and hematopoietic malignancy. Small cell carcinoma had the highest GC concordance, and its RD concordance was higher in pleural than in peritoneal fluids. Adenocarcinoma showed the highest concordance rates for both GC and RD. CONCLUSIONS: - This study illustrates the challenges associated with interpreting body fluid cytology, particularly in pericardial fluid, and the factors that may affect accurate diagnoses. The results also highlight the value of using multiple preparation types in challenging cases.

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.