Analytical and Clinical Sample Performance Characteristics of the Onclarity Assay for the Detection of Human Papillomavirus.

The objective of this study was to determine the result reproducibility and performance of the BD Onclarity human papillomavirus (HPV) assay (Onclarity) on the BD Viper LT platform using both contrived and clinical specimens. Reproducibility was assessed in BD SurePath liquid-based cytology (LBC) medium (SurePath) using contrived panels (HPV genotype 16 [HPV16] positive, HPV18 positive, or HPV45 positive) or clinical specimens (HPV16, -18, -31, -33/58, -45, or -52 positive or HPV negative). In addition, specimens from 3,879 individuals from the Onclarity trial were aliquoted prior to or following cytology processing and tested for HPV. Finally, specimens were collected using either the Cervex-Brush or Cytobrush (or Cytobrush/spatula) for comparison of HPV results. Contrived specimens showed >95% concordance with the expected results, and pooled clinical specimens had standard deviations and coefficients of variation ranging from 0.87 to 1.86 and 2.9% to 5.6%, respectively. For precytology and postcytology aliquot analyses, specimens showed >98.0% overall agreement and mean differences in cycle threshold (CT ) scores for HPV ranging from -0.07 to 0.31. Positivity rates were close between the Cervex-Brush and Cytobrush/spatula for all age groups tested. Onclarity results are reproducible and reliable, regardless of sample collection before or after cytology aliquoting. Onclarity performs well regardless of the method of specimen collection (Cervex-Brush or Cytobrush/spatula) for cervical cancer screening.

Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices.

BACKGROUND: In the United States, human papillomavirus (HPV) and Papanicolaou (Pap) testing (cotesting) for cervical screening in women ages 30 to 65 years is the preferred strategy, and cytology alone is acceptable. Recently, a proprietary automated test for identifying high-risk HPV types for primary cervical screening was approved by the US Food and Drug Administration. The objective of the current study was to document extensive cervical screening among these screening options. METHODS: To investigate the sensitivity of various testing options for biopsy-proven cervical intraepithelial neoplasia grade 3 or worse (≥ CIN3) and cancer, the authors reviewed 256,648 deidentified results from women ages 30 to 65 years at the time of cotest who had a cervical biopsy specimen obtained within 1 year of the cotest. RESULTS: A positive cotest result was more sensitive (98.8%; 4040 of 4090 cotests) for diagnosing ≥ CIN3 than either a positive HPV-only test (94%; 3845 of 4090 HPV-only tests) or a positive Pap-only test (91.3%; 3734 of 4090 Pap-only tests; P < .0001). A positive Pap-only result was more specific (26.3%; 66,145 of 251,715 Pap-only tests) for diagnosing ≥ CIN3 than a positive HPV-only test (25.6%; 64,625 of 252,556 HPV-only tests) or a positive cotest (10.9%; 27,578 of 252,558 cotests; P < .0001). Of 526 cervical cancers, 98 (18.6%) were HPV-only negative, 64 (12.2%) were Pap-only negative, and 29 (5.5%) were cotest negative. CONCLUSIONS: Compared with HPV-only testing, cotesting was more sensitive for the detection of ≥ CIN3 in women ages 30 to 65 years. The current data suggest that approximately 19% of women with cervical cancer may be misdiagnosed by an HPV-only cervical screen. It is important to consider these data as the guidelines for cervical cancer screening undergo revision. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

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 (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) and included 5 working groups; three 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 upon 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 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.

The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

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 cosponsored 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.

The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

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.

Analytical performance of Cervista HPV 16/18 genotyping test for cervical cytology samples.

BACKGROUND: Human papillomavirus (HPV) types 16 and 18 are the 2 most frequent types associated with cervical cancer. Identifying their presence or absence in cervical samples may assist in triaging women for subsequent management. The Cervista HPV 16/18 genotyping test specifically detects the presence of HPV 16 and 18 in ThinPrep cervical specimens. OBJECTIVES: The objective was to establish the analytical performance of the CERVISTA HPV 16/18 genotyping test. STUDY DESIGN: These studies were performed in support of a regulatory submission to the US Food and Drug Administration. Here we report the analytical sensitivity (limit of detection), accuracy compared to consensus L1 gene PCR/bi-directional sequencing, precision, reproducibility, and cross-reactivity (specificity) of the genotyping test. RESULTS: Analytical sensitivity for detection of HPV 16 and 18 ranged between 625 and 1250 copies/reaction for both types. When compared to PCR/sequencing for women with atypical squamous cells of undetermined significance cytology, the positive percent agreement was 94.1% (95% confidence interval [CI], 89.8-96.7) and the negative percent agreement was 85.7% (95% CI, 82.4-88.4). The test demonstrated high within-laboratory and inter-operator precision. Reproducibility within sites and between 3 testing sites resulted in 100% agreement with expected results (150 positive, 90 negative results). The genotyping test did not exhibit cross-reactivity to DNA from common low-risk HPV types and other microorganisms found in the human female reproductive tract. CONCLUSIONS: These analytical performance data support the use of CERVISTA HPV 16/18 genotyping test for the detection and differentiation of HPV 16 and 18 in ThinPrep cervical cytology specimens.

The Becton Dickinson FocalPoint GS Imaging System: clinical trials demonstrate significantly improved sensitivity for the detection of important cervical lesions.

Location-guided screening in cervical cytology offers a potentially significant advance over routine manual screening. A prospective, 2-armed, masked clinical trial of the BD FocalPoint GS Imaging System using SurePath slides (BD Diagnostics-TriPath, Burlington, NC) compared routine manual screening and quality control rescreening with computer-assisted, field-of-view screening and device-directed quality control rescreening. The results obtained in the 2 arms were compared with adjudicated reference diagnoses for each slide. Sensitivity, specificity, and negative predictive value were calculated for the detection of atypical squamous cells of undetermined significance and greater (ASC-US+), low-grade squamous intraepithelial lesion and greater (LSIL+), and high-grade squamous intraepithelial lesion and greater (HSIL+) groups. We evaluated 12,313 slides. The detection sensitivities for HSIL+ were increased by 19.6% (P < .0001) and for LSIL+ were increased by 9.8% (P < .0001) in the computer-assisted arm, with small statistically significant decreases in specificity. For ASC-US+ sensitivity and specificity, the study arms were not statistically different. Use of this system might be expected to improve accuracy for clinically important entities without increasing equivocal case detection.

Comparative analysis of conventional Papanicolaou tests and a fluid-based thin-layer method.

CONTEXT: A fluid-based, direct-to-vial method of thin-layer gynecologic cytology (ThinPrep Pap Test) is reported to be more effective than the conventional Papanicolaou test in the detection of squamous intraepithelial lesions. OBJECTIVE: This retrospective analysis evaluated the validity of the findings on the thin-layer method using case material at a large independent laboratory and represented a comparison of performance of both methods over an identical period. METHODS: Data for conventional and ThinPrep tests were compared for 2 periods. Period 1 included 1,421,080 conventional and 56,835 ThinPrep specimens, and period 2 included 564,270 conventional and 109,784 ThinPrep specimens. Squamous intraepithelial lesions were used to determine detection of disease. These 2 sets of data were also analyzed to eliminate effects of any selection bias toward ThinPrep for high-risk patients. RESULTS: Use of ThinPrep showed a greater than 100% increase in the detection rate of squamous intraepithelial lesions (1.3%-3.4% in period 1 and 1.3%-2.9% in period 2), which was statistically significant after correcting for selection bias. We also found a significant decrease in the false-negative proportion (57% in period 1 and 35% in period 2). There was a marked improvement (233%) in the detection of high-grade squamous intraepithelial lesions in high-risk cases and a decrease in the atypical squamous cells of undetermined significance to squamous intraepithelial lesion ratio from 3.1 to 1.5 in period 2. CONCLUSION: ThinPrep is better than the conventional Papanicolaou test in detecting squamous intraepithelial lesions and is a superior screening test in detection of precancerous changes of the cervix.