Laboratories as the Core for Health Systems Building.

If it is accepted that health care access to diagnosis and treatment is a universal human right, the principal challenge is how to deliver that health care to all people. Health systems that function are the most effective way to deliver such care; these health systems should cover all of the diseases facing a population. The central role of laboratories in making medical decisions is crucial. If organizations engaged in health systems building tackle a disease category, such a cancer, multiple modalities within and outside of the laboratory have to be improved or installed to make an effective system.

Building a laboratory workforce to meet the future: ASCP Task Force on the Laboratory Professionals Workforce.

OBJECTIVES: To analyze the demand for services from the nation's medical laboratories, which is predicted to dramatically increase as our citizens age and millions receive insurance coverage through the Affordable Care Act. METHODS: A systematic review of relevant publications and databases was conducted to assess the current state of the nation's medical laboratory workforce and to examine the impact of population demographics and health reform on workforce development to address the future demand for laboratory services. RESULTS: Building a Laboratory Workforce to Meet the Future, a new report from the American Society for Clinical Pathology (ASCP), provides a comprehensive strategy to address the future workforce needs of the nation's medical laboratories to meet this demand to provide timely, accurate, and safe patient care and to fully realize the benefits of personalized medicine. CONCLUSIONS: The report, from the ASCP Task Force on the Laboratory Professionals Workforce, is a comprehensive review of the myriad of factors affecting recruitment and retention of qualified laboratory professionals and provides a set of thoughtful recommendations outlining a multifaceted approach to bolster the pipeline of potential candidates for the profession as well as leadership in health care.

A cross-sectional study of a prototype carcinogenic human papillomavirus E6/E7 messenger RNA assay for detection of cervical precancer and cancer.

PURPOSE: To evaluate carcinogenic human papillomavirus (HPV) mRNA for E6 and E7 mRNA detection on clinical specimens to identify women with cervical precancer and cancer. EXPERIMENTAL DESIGN: We evaluated a prototype assay that collectively detects oncogenes E6/E7 mRNA for 14 carcinogenic HPV genotypes on a sample of liquid cytology specimens (n=531), masked to clinical data and to the presence of HPV genotypes detected by PGMY09/11 L1 consensus primer PCR assay. RESULTS: We found an increasing likelihood of testing positive for carcinogenic HPV E6/E7 mRNA with increasing severity of cytology (P(Trend) < 0.0001) and histology (P(Trend) < 0.0001), with 94% of cervical intraepithelial neoplasia grade 3 (CIN3) histology cases (46 of 49) and all five cancer cases testing positive for carcinogenic HPV E6/E7 mRNA. Overall, fewer specimens tested positive for carcinogenic HPV E6/E7 mRNA than for carcinogenic HPV DNA (P<0.0001, McNemar's chi(2) test), especially in women with

A comparison of the clinical utility of p16(INK4a) immunolocalization with the presence of human papillomavirus by hybrid capture 2 for the detection of cervical dysplasia/neoplasia.

BACKGROUND: Evidence suggests that overexpression of p16(INK4a) protein indicates infection and genomic integration of high-risk human papillomavirus (HR HPV) and predicts progression to cervical high-grade squamous intraepithelial lesions (HSILs) and carcinoma. The authors compared the ability of p16(INK4a) and HR HPV detection by Hybrid Capture 2 (HC2) to detect the presence of significant cervical disease. METHODS.: Four hundred ThinPrep specimens (100 each in 4 categories: 100 specimens that were negative for intraepithelial lesions, 100 specimens of atypical squamous cells of undetermined significance [ASC-US], 100 specimens of low-grade squamous intraepithelial lesions [LSILs], and 100 specimens of HSILs) were analyzed. p16(INK4a) protein was immunolocalized using a specific monoclonal antibody, and the detection of HR HPV in all 400 specimens was determined using HC2. RESULTS: p16(INK4a) was found to be positive in 78% of HSIL specimens, 42% of LSIL specimens, and 36% of ASC-US specimens; whereas HC2 was positive in 92% of HSIL specimens, 81% of LSIL specimens, and 45% of ASC-US specimens. In the HSIL category, the sensitivity, which was calculated using Grade 2 or greater cervical intraepithelial neoplasia as the endpoint, was 78% (50 of 66 specimens) for p16(INK4a) and 91% (60 of 66 specimens) for HC2. For LSIL, the sensitivity was 75% (3 of 4 specimens) for p16(INK4a) and 100% (4 of 4 specimens) for HC2. In the ASC-US category, the sensitivity was 89% (8 of 9 specimens) for p16(INK4a) and 100% (9 of 9 specimens) for HC2. Overall, the sensitivity for HSIL was 92% for HC2 and 78% for p16(INK4a). The specificity for HC2 was 8.3% for HSIL, 16.9% for LSIL, and 48.7% for ASC-US; whereas the specificity for p16(INK4a) was 25% in HSIL, 59.1% in LSIL, and 68.4% in ASC-US. The overall specificity was 25% for HC2 and 56% for p16(INK4a). CONCLUSIONS: Although both p16(INK4a) and HC2 may aid in the clinical management of patients with clinically significant lesions, HC2 was found to have greater sensitivity, and p16(INK4a) greater specificity. The labeling of normal cells and bacteria may preclude the use of p16(INK4a) in automated screening or nonmorphologic assays.

Pilot study of a commercialized human papillomavirus (HPV) genotyping assay: comparison of HPV risk group to cytology and histology.

We evaluated a commercialized PCR assay, Linear Array, that detects 37 human papillomavirus (HPV) genotypes, using a sample of liquid cytology specimens (n = 534). We found a strong association of an increasing level of HPV risk (HPV type 16 [HPV16] > HPV18 > other carcinogenic types > noncarcinogenic types > negative specimens) with increasing severities of cytologic interpretations (P(Trend) < 0.0005) and histologic diagnoses (P(Trend) < 0.0005).

Results of multiple-slide, blinded review of Papanicolaou slides in the context of litigation. Determining what can be detected regularly and reliably.

BACKGROUND: Multiple-slide, blinded review has been endorsed by several cytology and pathology organizations as the most appropriate method for the review of cervicovaginal specimens in the context of litigation. This process involves review of litigation slides in a blinded manner by multiple independent cytotechnologists and the comparison of those results with those of validation cases that are comprised of known abnormalities with biopsy follow-up. To the authors' knowledge, the results of this method have not been previously published. METHODS: The results of the blinded review program at the Center for Cytopathology and Molecular Research at the Medical University of South Carolina for the years 1998-2004 were reviewed. RESULTS: A total of 135 litigation slides and 122 validation slides were reviewed. The interpretations of these cases were found to be significantly different (P < 0.001). Litigation cases were significantly more likely to be interpreted as either negative for intraepithelial lesion (NIL) or atypical squamous cells/atypical glandular cells (ASC/AGC) (P < 0.001). The results appeared to be independent of the individual cytotechnologists involved. Approximately 10% of litigation cases were called at least ASC/AGC by all observers and 4% were interpreted as NIL by all observers. For litigation cases, ASC/AGC was found to be just as reproducible as high-grade squamous intraepithelial lesion. The results demonstrated that only 10% of litigation cases are regularly and reliably identified as abnormal, whereas a single review as performed by an expert cytologist can be expected to classify 56% of cases as abnormal. CONCLUSIONS: This program suggests that a majority of litigation cases are not regularly and reliably identified as abnormal, and a single review will routinely overestimate the percentage of cases that are identified regularly and reliably.

A novel filtration-based processing method of liquid cytology specimens for human papillomavirus DNA testing by hybrid capture II.

We evaluated a more efficient method of processing liquid-based cervical cytology specimens for human papillomavirus (HPV) DNA testing by Hybrid Capture II (HCII). Aliquots were made from 701 specimens in the following sequence: 4.0, 2.0, 1.0, 0.5, and 1.5 mL. The 4.0-mL aliquot was processed by the standard method (STP), and half of the processed material was tested by HCII. Other aliquots were processed with a new, filtration-based processing method (NPM). The 2.0-mL NPM aliquot had HCII test performance most similar to the STP, ie, similar HCII positivity (P = .4) and good test agreement (kappa = 0.85, 95% confidence interval [CI], 0.80-0.89). The 194 cytologic negatives had greater positivity by STP (P = .04) compared with the 2.0-mL aliquot processed by NPM; between-method agreement was modest (kappa = 0.54, 95% CI, 0.36-0.72). A lower positive cut point for the 2.0-mL NPM aliquot partially abrogated this minor difference. In 241 specimens diagnosed as low-grade and 31 as high-grade squamous intraepithelial lesions, there were no significant differences in HPVpositivity (>85% and 90%, respectively) between STP and NPM. NPM reduces specimen handling and decreases total testing time by approximately 33% without significant losses in HCII test performance.

Blinded review of Papanicolaou smears in the context of litigation.

BACKGROUND: Blinded review has been endorsed by several cytology and pathology organizations as the most appropriate method for the review of cervicovaginal specimens in the context of litigation. Methods for determining the statistical validity of this method were evaluated. METHODS: First, the authors calculated the sample size needed to detect various differences in case difficulty or ease of interpretation, in which ease of interpretation is defined as the percentage of the time a case could be identified as abnormal by routine screening. Very easy cases could be identified most reliably, whereas more difficult cases were detected less regularly and less reliably. Using construct sample sizes, the authors calculated the number of abnormal reviews that may be helpful to conclude that the case's difficulty or ease of interpretation was statistically significantly different from another case of a specified difficulty. Finally, they examined the effect of using two separate cutoff parameters to make these distinctions. RESULTS: Depending on the threshold chosen, it was determined that improvements in the statistically meaningful distinctions may be made using 15 or 20 reviews. To distinguish between routine false-negative cases (ease of detection, 40%) and routine cases (ease of detection, 80%), the thresholds may be set at 5 of 10 reviews (a case that would not be detected regularly and reliably in any given laboratory) and 7 of 10 reviews (defining a case that would be identified regularly and reliably), respectively. CONCLUSIONS: The authors provide data that can be used to interpret the results of a blinded review in a statistically appropriate manner. To improve the utility of blinded reviews, the standards are defined explicitly.