Biomedical subjects

D C Wilbur

Publications and source records attributed to D C Wilbur.

46 records · Page 3Linked to original sources

PubMedDate not supplied

Human papillomavirus. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cervical squamous cell carcinomas, adenocarcinomas and their precursors are caused by the human papillomavirus (HPV). Although HPV appears to be essential to the transformation of these epithelial cells, it is not sufficient, and a variety of cofactors and molecular events must take place between when an HPV infection occurs and a cervical cancer or its precursor develops. This review examines the data supporting these contentions, briefly outlines the molecular events that occur, considers the epidemiology and natural history of the disease, and details the implications of using HPV detection and typing in both clinical management and population-based screening programs. CONSENSUS POSITION: 1. Based on the available molecular, clinical and epidemiologic data, a subset of HPVs are unequivocally the etiologic agents for cervical cancers and their precursors. 2. Different mucosotropic HPVs have varying neoplastic potential. However, the great majority of cervical HPVs have oncogenic potential. Since oncogenic HPV-induced epithelial transformation to a high grade lesion or cancer is rare relative to the rate of infection, the term high risk is discouraged. 3. HPV's interaction with host cells has two principal biologic consequences: a) All anogenital HPVs induce low grade squamous lesions, which are the morphologic correlate of a productive infection. b) Rarely, HPVs induce a proliferative epithelial phenotype that pathologists recognize as a high grade lesion and that is the proximate cytohistologic precursor of invasive cervical carcinoma. 4. HPV biology and issues of practical clinical management should be reflected in the classification systems used for cytologic and histologic diagnosis. ONGOING ISSUES: The molecular identification of HPVs (HPV testing) potentially may be very useful for primary screening or secondary triage of patients with certain lesions. However, the technology available to the practicing clinician is still evolving. Optimization of type spectrum, sensitivity, specificity and ease of use is under development. Data regarding these factors as well as a clear cost benefit analysis are sparse or pending in several large trials. Until such data are available, caution in clinical implementation of HPV testing is warranted.

Adenocarcinoma↗

PubMedDate not supplied

Computerized screening devices and performance assessment: development of a policy towards automation. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The extension of automation to the diagnostic assessment of clinical materials raises issues of professional responsibility, on the part of both the medical professional and designer of the device. The International Academy of Cytology (IAC) and other professional cytology societies should develop a policy towards automation in the diagnostic assessment of clinical cytologic materials. CONSENSUS POSITION: The following summarizes the discussion of the initial position statement at the International Expert Conference on Diagnostic Cytology Towards the 21st Century, Hawaii, June 1997. 1. The professional in charge of a clinical cytopathology laboratory continues to bear the ultimate medical responsibility for diagnostic decisions made at the facility, whether automated devices are involved or not. 2. The introduction of automated procedures into clinical cytology should under no circumstances lead to a lowering of standards of performance. A prime objective of any guidelines should be to ensure that an automated procedure, in principle, does not expose any patient to new risks, nor should it increase already-existing, inherent risks. 3. Automated devices should provide capabilities for the medical professional to conduct periodic tests of the appropriate performance of the device. 4. Supervisory personnel should continue visual quality control screening of a certain percentage of slides dismissed at primary screening as within normal limits (WNL), even when automated procedures are employed in the laboratory. 5. Specifications for the design of primary screening devices for the detection of cervical cancer issued by the IAC in 1984 were reaffirmed. 6. The setting of numeric performance criteria is the proper charge of regulatory agencies, which also have the power of enforcement. 7. Human expert verification of results represents the "gold standard" at this time. Performance characteristics of computerized cytology devices should be determined by adherence to defined and well-considered protocols. Manufacturers should not claim a new standard of care; this is the responsibility of the medical community and professional groups. 8. Cytology professionals should support the development of procedures that bring about an improvement in diagnostic decision making. Advances in technology should be adopted if they can help solve problems in clinical cytology. The introduction of automated procedures into diagnostic decision making should take place strictly under the supervision and with the active participation and critical evaluation by the professional cytology community. ONGOING ISSUES: Guidelines should be developed for the communication of technical information about the performance of automated screening devices by the IAC to governmental agencies and national societies. Also, guidelines are necessary for the official communication of IAC concerns to industry, medicolegal entities and the media. Procedures and guidelines for the evaluation of studies pertaining to the performance of automated devices, performance metrics and definitions for evaluation criteria should be established.

Automation↗

PubMedDate not supplied

Computerized training and proficiency testing. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Computerized technologies probably will revolutionize the field of gynecologic cytology in the next century. Such technologies will be useful in both training and evaluating proficiency. However, manual screening/review of gynecologic cytology preparations is the current "gold standard" for both training and assessment of proficiency. CONSENSUS POSITION: Training programs for cytotechnologists and pathologists should provide instruction and experience in new technologies, but their introduction may depend on the availability of equipment and staff. Advantages of digital images for training include standardization of teaching sets and interactive capabilities, allowing educational feedback. Computerized support/assistance devices aid in complete screening of the slide during training and provide feedback to cytologists on screening techniques. Liquid-based cytopreparatory instruments facilitate multiple glass slides for teaching or testing. Proficiency testing (PT) in cytology has similar quality assurance goals as in other areas of the laboratory, but the subjective nature of cytologic analysis poses many challenges for implementation. There is consensus that all cytology practitioners would like to know the proficiency of the laboratory. However, the majority question the value and validity of any large-scale formal testing programs. Locator and diagnostic skills are both critical in cytology, but assessment of each skill may occur in different ways using computerized technologies. Any type of assessment should provide educational feedback to participants. Psychometric issues in PT include the consideration of different types of validity, including face, content, construct and criterion related. The reliability or consistency of the testing event is also critical. A valid and reliable correlation between work performance and performance on a PT needs to be established. The goal is to ensure that PT will identify submarginal practitioners and that persons successful on PT are in fact competent. Any cytology PT program should also be considered in the context of other laboratory quality assurance tools and the entire cervical cancer screening program. Regulatory agencies should evaluate entire laboratory performance, while each laboratory director should assume primary responsibility for evaluating and documenting the competency and daily performance of each practicing cytologist. Professional scientific organizations should take the lead in recommending methods and standards of performance assessment. ONGOING ISSUES: A reliable method of correlating daily competency with results on PT is not yet established. Methods may evolve ever time using new technologies. The use of computerized techniques and images for assessment will require careful deliberation by experts as well as validation by practicing cytologists. Variables include diagnostic categories for testing, numbers of challenges per testing event, types of slide preparations and characteristics of the digital images. Availability of equipment and staff will affect the introduction of new technologies in different regions.

Cell Biology↗

PubMedDate not supplied

The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice.

OBJECTIVE: To evaluate the effectiveness of the AutoPap System in detecting abnormal and normal cervical smears when used in a primary screening/quality control mode, as compared with currently established laboratory practices. STUDY DESIGN: Slides were obtained prospectively and were initially processed in the routine fashion with cytotechnologist screening followed by 10% random quality control rescreening. Slides were then processed on the AutoPap System and allocated into the following groups: (1) approximately 25% of the lowest-ranking slides were placed in the laboratory's archives as within normal limits; (2) the remaining approximately 75% of slides were subjected to manual screening. Approximately 15% of the highest-ranking slides in this group underwent quality control rescreening. For each slide needing manual screening, the cytotechnologist was supplied with a report giving the ranking score of that slide. All discrepant slides for either adequacy or diagnosis were subjected to a truth-determination process. The results obtained from the two arms of the protocol were then compared. RESULTS: The AutoPap System-assisted arm of the study was superior to the current practice arm for the identification of abnormal slides at the level of atypical squamous cells of undetermined significance and above (ASCUS+), low grade squamous intraepithelial lesion (LSIL) and higher LSIL+. AutoPap System-assisted practice was equivalent to current practice for the identification of unsatisfactory and satisfactory but limited by slides. All results showed statistical significance. In addition, AutoPap System-assisted practice in the study indicated improved specificity of diagnosis. CONCLUSION: AutoPap System-assisted practice shows superior sensitivity and specificity when compared to current practice. Its clinical use as a primary screening device should improve the overall practice of cervical cytology as well as provide potential enhancement in overall laboratory productivity.

Algorithms↗

PubMedDate not supplied

A feasibility study of the AutoPap system location-guided screening.

OBJECTIVE: To study the feasibility of AutoPap System location-guided screening and to evaluate the accuracy of the AutoPap System in selecting locations of potentially abnormal cellular material, the accuracy of triaging slides using the selected locations and the improvement in laboratory accuracy and workload reduction resulting from a combination of location-guided rescreening and AutoPap System primary screening. STUDY DESIGN: For the study, 683 conventionally prepared cervical cytologic smears (263 WNL, 184 atypical squamous cells of undetermined significance/atypical glandular cells of undetermined significance, 173 low grade squamous intraepithelial lesions, 55 high grade squamous intraepithelial lesions and 8 cancer slides) were acquired from nine laboratories. The study slides were independently screened to establish study reference diagnoses. The slides were processed on the AutoPap System and screened by cytotechnologists who were guided by the field of view (FOV) locations provided by the AutoPap System. The location-guided information was used either for initial manual screening (location-guided screening or after initial manual screening of the entire slide (location-guided rescreening). The results were compared to the study reference diagnoses. Sensitivity and workload reduction figures were estimated for different slide populations. RESULTS: The accuracy of location-guided slide triage was high and did not vary significantly over different slide populations. Also, for > 80% of the abnormal slides, the AutoPap System-selected FOV slide locations did contain the most diagnostic cells, which were used to assign an accurate diagnosis to the slide. By combining location-guided rescreening with AutoPap primary screening, the estimated overall location-guided screening false negative fraction (FNF) for LSIL+ slides was approximately 40 times lower than the cytotechnologist-only FNFs, and this improvement was achieved-even at a no review rate of 70%. CONCLUSION: The feasibility study results showed that the AutoPap System location-guided screening process can triage slides accurately and enhance the overall accuracy of slide diagnosis. The combination of location-guided rescreening and AutoPap primary screening could improve the accuracy and workload of the laboratory.

Automation↗

PubMedDate not supplied

Clinical trials of the CytoRich specimen-preparation device for cervical cytology. Preliminary results.

OBJECTIVE: To obtain preliminary data on the Roche CytoRich thin-layer system for the preparation of gynecologic cytology specimens, derived from a preclinical startup evaluation of the instrument and comparing the CytoRich method to conventional smears. STUDY DESIGN: At six different clinical sites, 286 pairs of conventional and CytoRich slides derived from the same patient sample were compared for the following: final Bethesda classification diagnosis, specimen adequacy and presence of microorganisms. RESULTS: The study showed agreement between the methods for an exact Bethesda diagnosis in 78% and agreement within one Bethesda diagnosis category in 95%. The CytoRich method diagnosed more cases of squamous intraepithelial lesion (SIL) than did the conventional method, and the differences in SIL detection were statistically significant. The CytoRich method identified similar numbers of cases with microorganisms as did the conventional smears, and the CytoRich system improved overall specimen adequacy as compared to the conventional method, with fewer cases of unsatisfactory and less-than-optimal smears. CONCLUSION: The CytoRich method may improve the overall sensitivity and specificity of the cervical cytology procedure. Clinical trials to verify these preliminary data are ongoing.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Atypical squamous cells of undetermined significance. Stratification of the risk of association with, or progression to, squamous intraepithelial lesions based on morphologic subcategorization.

OBJECTIVE: To analyze follow-up data on atypical squamous cells of undetermined significance (ASCUS) based on morphologic characteristics. STUDY DESIGN: Five years of follow-up was obtained on a cohort of 437 consecutive patients from 1986 who had initial diagnoses of ASCUS, with a further categorization of type based on the maturity of the atypical cells. All such categorizations were made on the basis of specific cytologic criteria. Follow-up cytology and/or biopsy was available on 366 patients. RESULTS: During the follow-up period, 40 patients (13.5%) with ASCUS were diagnosed as having a squamous intraepithelial lesion (SIL); 15 (5%) were interpreted as high grade. When stratified by type of ASCUS based on cellular maturity, the following association/progression rates were noted: mature ASCUS, 10%; metaplastic ASCUS, 24%; and immature metaplastic ASCUS, 42%. In metaplastic and immature metaplastic ASCUS cases, high grade SIL accounted for 42% and 60% of those subsequently diagnosed with a squamous intraepithelial lesion, respectively, versus 30% for mature ASCUS. CONCLUSION: With well-defined and consistent criteria for the diagnosis of the variety of "squamous atypias," a stratification of risk of progression to or association with SIL can be made. When features of metaplasia and immature metaplasia are noted in the cells of ASCUS, patients were observed to be at increasingly greater risk for the detection of SIL; those cases were proportionately more likely to be high grade.

Adult↗

PubMedDate not supplied

Sensitivity of the AutoPap 300 QC System for cervical cytologic abnormalities. Biopsy data confirmation.

OBJECTIVE: To assess the AutoPap 300 QC System's sensitivity to cases of high grade squamous intraepithelial cervical lesion and invasive cervical cancer, a comparison of outcome was made in cases that had surgical biopsy confirmation. STUDY DESIGN: The sensitivity of the device to biopsy-confirmed diagnostic categories at the level of high grade squamous intraepithelial lesion (HSIL) and greater was calculated. At two of six clinical trial sites, biopsy data were available and were compared to device scores indicating whether a case would or would not be selected for 10% or 20% quality control rescreening. RESULTS: In 86 biopsy-positive cases that had a cytologic diagnosis of HSIL or greater, the device indicated inclusion in the 10% or 20% review fraction for 66 slides (77%) and 74 (86%), respectively. This figure indicated an approximately eightfold improvement in the ability of the device to include such cases for quality control rescreening when compared to a 10% random case selection process. CONCLUSION: These data showed that the sensitivity of the AutoPap in identifying cases of HSIL and greater was similar to that previously calculated for these diagnostic categories in clinical trials, when calculated on the basis of an alternate or "higher" standard of tissue confirmation.

Biopsy↗

PubMedDate not supplied

Testing for human papillomavirus: basic pathobiology of infection, methodologies, and implications for clinical use.

New molecular biological evidence has recently emerged, strongly implicating the human papillomavirus (HPV) as playing an etiologic role in the development of neoplasias of the genital tract. As technologies advance, the ability to test for the presence of HPV has become simpler, more reliable, and less expensive. A great deal of controversy has arisen regarding the effective and proper utilization of these new tests in the management of HPV infections. This review will detail the new evidence implicating the putative role of HPV in neoplasia and the current methodologies available for assessing the presence of HPV in clinical samples and will describe the current controversy surrounding their utilization.

Female↗

PubMedDate not supplied

Behçet's disease in a vaginal smear. Report of a case with cytologic features and their distinction from squamous cell carcinoma.

A 52-year-old woman who had undergone a hysterectomy 15 years previously for benign disease presented with ulcerative lesions on the perigenital skin and external genitalia. A Papanicolaou smear of the vagina, unaccompanied by any history, showed a heavy, purulent exudate and many isolated pleomorphic and keratinizing squamous cells. The findings were suggestive of squamous cell carcinoma. Subsequently obtained clinical data revealed a long-standing history of ulcerating oral and genital lesions of Behçet's disease. Biopsy confirmed the nonneoplastic ulcerative nature of the process. Given this cytologic pattern, the presence of a substantial purulent exudate and the identification of cytologic features suggesting reparative epithelial changes should caution the observer against an interpretation of squamous cell carcinoma and suggest the presence of a nonneoplastic ulcerative process.

Behcet Syndrome↗