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Context.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16 INK4a immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs)., Objective.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses., Design.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available., Results.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall ( P trend ≤ .001) and within each HPV risk group ( P trend ≤ .001 except for low-risk HPV [ P trend < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group ( P trend < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies ( P < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL + cytology, or to be diagnosed as CIN3 + by the EP ( P < .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies ( P < .001)., Conclusions.—: p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.

Context: The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2011 gynecologic cytology survey., Objective: To provide a cross-sectional survey of gynecologic cytology practices in 2010., Design: In 2011, a survey was sent to 1604 laboratories participating in the College of American Pathologists gynecologic cytology interlaboratory comparison education program and proficiency testing programs requesting data from 2010 on the following topics: terminology/reporting, cytotechnologist workload, quality assurance, reagents, and ancillary testing., Results: Six hundred and twenty-five laboratories (39%) replied to the survey. The nonstandard use of "low-grade squamous intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion" is used by most laboratories to report the presence of low-grade squamous intraepithelial lesion with possibility of high-grade squamous intraepithelial lesion. Most laboratories also report the presence or absence of cells from the transformation zone. Most respondents do not limit cytotechnologist screening workload during the work shift. Only about one-third of laboratories (188 of 582; 32%) use image-assisted screening devices. Rapid prescreening as a quality assurance measure is used by only 3.5% (21 of 594) of the laboratories. When used for screening, most laboratories use the imager for retrospective review of slides to detect human locator and interpretive errors. Most laboratories receive both liquid-based cytology samples (mainly ThinPrep, Hologic, Marlborough, Massachusetts) and conventional Papanicolaou tests. Expiration dates of liquid-based cytology test vials are not usually recorded., Conclusions: The field of gynecologic cytology is evolving rapidly. These survey results offer a snapshot of national gynecologic cytology practices in 2010.

Context: In cytology proficiency testing (PT), participants fail for incorrectly interpreting a high-grade squamous intraepithelial lesion or cancer (HSIL+) Papanicolaou test result as negative. This penalty may lead to a false-positive interpretation of negative slides as HSIL+ to avoid failure., Objective: To investigate factors related to false-positive responses in a PT versus an educational environment., Design: We analyzed 420,079 responses from 9414 validated negative reference slides in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytopathology (PAP Education) and compared them with responses from the Gynecologic Cytology Proficiency Testing Program for the percentage of false-positive (HSIL+) interpretations in each of 7 negative subcategories. We evaluated the influence of preparation type (ThinPrep, SurePath, and conventional Papanicolaou test), participant type (pathologist or cytotechnologist), and program time interval (preproficiency test or PT) on a false-positive response., Results: Reference diagnosis and participant type, but not preparation type, were statistically correlated to false-positive responses. The interaction between program time interval and participant type was also significant. Pathologists had higher rates of false-positive results on preproficiency test (1.2% [800 of 68,690]) than they did on PT (0.8% [993 of 129,857]). Cytotechnologists had no differences between program time intervals (preproficiency, 0.9% [515 of 63,281] versus PT, 1.0 [1231 of 121,621]; P = .91). Negative subcategories frequently mistaken for HSIL+ were reparative changes (4.7% [427 of 9069]), atrophic vaginitis (1.8% [18 of 987]), and negative for intraepithelial lesion or malignancy (1.2% [2143 of 178,651]), but during PT, false-positive rates were significantly increased only for the negative for intraepithelial lesion or malignancy and herpes simplex virus (P < .001)., Conclusions: Pathologists had lower false-positive rates in the Gynecologic Cytology Proficiency Testing Program than they did in PAP Education, but participants were more likely to report a false-positive response (HSIL+) for negative for intraepithelial lesion or malignancy and herpes simplex virus in the Gynecologic Cytology Proficiency Test Program.

Context: Anal cytology is being used more frequently for anal cancer screening, yet many cytologists are unfamiliar with it., Objective: To describe the performance of anal cytology in the College of American Pathologists' Interlaboratory Comparison Program in Non-Gynecologic Cytology (CAP NGC) educational slide program during a 6-year time span, from 2006 to 2011, using participant responses (pathologist, cytotechnologist, and laboratory)., Design: Concordance rates for the target diagnosis and general category for each slide challenge were analyzed. Four main factors were included in the analysis: (1) general category or specific responses, (2) program year from 2006 to 2011, (3) participant type (pathologist, cytotechnologist, or overall laboratory), and (4) preparation type (liquid-based or conventional)., Results: Participants most frequently correctly classified negative for intraepithelial lesion or malignancy, low-grade squamous intraepithelial lesion, and herpes simplex virus infection, with concordance rates of 78.8%, 85%, and 80.2%, respectively. Performance on challenges with target diagnoses of high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, and ameba was poor, with concordance rates of 57.1%, 56.2%, and 41.5%, respectively. Significant improvement during the 6 years was seen in the concordance rates of participants' responses for low-grade squamous intraepithelial lesion challenges but not for HSIL. There was no significant difference in performance by slide preparation type., Conclusions: The poor performance on anal cytology in the CAP NGC program, especially with regard to correct identification of HSIL and squamous cell carcinoma, indicates that there is a need for continued education about anal cytology.

Context: The College of American Pathologists' Interlaboratory Comparison Program in Gynecologic Cytology has seen an increase in enrollment in liquid-based Papanicolaou test challenges with a decrease for conventional Papanicolaou tests. Trichomonas vaginalis can be difficult to identify in all preparation types., Objectives: To evaluate 20 years of participant results from the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology for Trichomonas to ascertain whether performance has changed because of the introduction of liquid-based Papanicolaou and proficiency testing., Design: Concordance rates for the target diagnosis of Trichomonas vaginalis were evaluated for 167,956 participant responses (1990-2010). A nonlinear mixed model was fit with participant type, preparation type, and a 2-level program year (1990-2005 and 2006-2010) reflecting before and after proficiency testing began. A repeated-measures component allowed modeling of the slide-specific performance to ensure that the overall results were not based on the performance of a few slides., Results: Cytotechnologists had higher concordance with the target diagnosis than did pathologists (89.8% [72,992 of 81,319] versus 83.4% [72,271 of 86,637], P < .001) and better performance for each preparation type (P = .003). Concordance initially dropped after the introduction of proficiency testing (P < .001) for conventional and liquid-based (SurePath) preparations by both participant types, followed by quick, parallel improvement., Conclusions: Performance is high in the detection of Trichomonas vaginalis in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology. Liquid-based Papanicolaou and proficiency testing minimally affected participant performance. Cytotechnologists performed better over time and across preparation types than did pathologists, although pathologists showed performance results parallel to that of the cytotechnologists. Awareness of the performance differences by pathologists and cytotechnologists, as well as their difference in proficiency among liquid-based techniques, may help ensure accurate results in clinical practice.

Context: Atrophic vaginitis is a commonly reported subset of Papanicolaou test results that are negative for intraepithelial lesion or malignancy, but interpretive criteria overlap with atrophic changes and other entities, hindering concordance among observers., Objectives: To report on the participant concordance from 2000 to 2009 in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytopathology, with a reference interpretation of atrophic vaginitis, and to investigate cytologic features of good and poorly performing slides to identify criteria useful in the interpretation of atrophic vaginitis., Design: We summarized 18 302 responses from the program for slides with a reference interpretation of atrophic vaginitis. We randomly selected 18 Papanicolaou test results (3 conventional, 4 SurePath, and 11 ThinPrep) from good and poor performers for prospective, blinded criteria scoring for the following features: abundance of neutrophils, more than 100 degenerating parabasal cells, more than 25% necrotic background, more than 100 pseudoparakeratotic cells, and the presence of stripped or streaked nuclei, histiocytes, and superficial or intermediate squamous cells., Results: Most Papanicolaou test results (>90%) with a specific reference interpretation of atrophic vaginitis were categorized as negative. Cytotechnologists are more likely than pathologists are to label it negative for intraepithelial lesion or malignancy (NILM) and are equally likely to mistake it for a high-grade lesion. Degenerating parabasal cells, pseudoparakeratosis, and necrotic background are associated with atrophic vaginitis (P  =  .001) on Papanicolaou. Abundant neutrophils (>100 per ×400 field) are also significantly correlated (P  =  .01)., Conclusions: Exact concordance to atrophic vaginitis is less than 90%. Most of the discrepancies are negative results for intraepithelial lesion or malignancy. Advanced atrophic features are as significant as neutrophils are to the interpretation of atrophic vaginitis.

The terminology for human papillomavirus(HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was co-sponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.

Context: Herpes simplex virus (HSV) is a common sexually transmitted disease that is decreasing in prevalence. Herpes simplex virus challenge cases have performed well in the educational College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. However, since gynecologic cytology proficiency testing (PT) was instituted, performance of HSV challenge cases has worsened., Objective: To determine if the decrease in performance for HSV challenges is due to inexperience in identifying herpes virus or "gaming" of PT., Design: We compare graded (field-validated) and ungraded (educational) slides with HSV prior to PT (1991- 2005) and after PT (2006 and 2007) in an attempt to characterize changes in performance of slides demonstrating purely HSV cellular features. All HSV slides were negative for intraepithelial lesion with the specific reference interpretation of HSV. Slides were excluded from analysis if they demonstrated more than one diagnostic category or had squamous intraepithelial lesion in addition to HSV changes., Results: A total of 40 634 HSV responses were evaluated. A significant difference existed in the diagnosis of HSV in PT compared with graded challenges prior to PT (96.6 versus 98.6; P < .001). No difference was seen in educational challenges pre-PT and post-PT (P = .14). No difference was present between slide preparation type; however, a difference was seen between cytotechnologist and pathologist response., Conclusions: There is a change in the performance of slide challenges demonstrating the cellular features of HSV in PT, most likely due to testing strategies of participants, rather than lack of recognition of HSV secondary to decreased prevalence.

Context: Candida may elicit cellular changes on otherwise negative screening Papanicolaou tests that may be misinterpreted as atypical squamous cells of undetermined significance. Although these changes have been correctly interpreted in the educational program of the College of American Pathologists, the Interlaboratory Comparison Program in Gynecologic Cytology, the performance of negative slides with Candida faltered when the same field validated slides were included in proficiency testing (PT)., Objective: To identify the performance differences of negative for intraepithelial lesion (NILM) Candida challenges before and after PT., Design: We compare the performance of NILM College of American Pathologists slides with Candida as a single reference diagnosis, prior to PT (1991-2006) and after PT (2006-2007)., Results: There were 147,186 responses for slides with NILM Candida from the College of American Pathologists programs from 1991 through 2007. After PT, 79.7% of incorrect participant responses identified Candida as Category C (low-grade squamous intraepithelial lesion), whereas prior to PT only 59.5% of the incorrect diagnoses were low-grade squamous intraepithelial lesion (P < .001) in the field-validated component of the program. Validated Candida slides performed significantly more poorly in PT (97.2%) than prior to PT (98.3%) (P < .001). Candida challenges performed better in the educational component post-PT (98.3% versus 97.2%; P < .001). Cytotechnologists (97.9%) identified Candida more frequently than pathologists (97.3%) (P < .001) and ThinPrep preparations performed the best of all preparation types., Conclusions: Proficiency testing adversely affects the performance of participants in the identification of NILM Candida. Slides with Candida are more likely to be identified as low-grade squamous intraepithelial lesion in a PT exercise. Misidentification is not due to lack of recognition but most likely an attempt of test takers to optimize their likelihood of passing the examination.