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Biomedical subjects

Daron G Ferris

Publications and source records attributed to Daron G Ferris.

At least 19 recordsLinked to original sources

Prediction of cervical histologic results using an abbreviated Reid Colposcopic Index during ALTS.

OBJECTIVE: The purpose of this study was to determine the accuracy of an abbreviated Reid Colposcopic Index (RCI) to detect cervical intraepithelial neoplasia (CIN) 2 and CIN 3 during the National Cancer Institute (NCI) ASCUS LSIL Triage Study (ALTS). STUDY DESIGN: Colposcopists from 4 ALTS clinical centers indicated an RCI score after colposcopically examining subjects. Colposcopy quality control reviewers also documented an RCI score for the same subjects after assessing their digitized cervical images. Associations of colposcopist and reviewer RCI scores with histologic results were evaluated. Agreement rates between colposcopists and reviewers were calculated for colposcopic impression. RESULTS: Overall RCI score agreement was poor (weighted Kappa = 0.17). The sensitivity, specificity, positive and negative predictive values of a colposcopist's RCI score of >3/6 to detect CIN 3 or worse were 37.3% (95% CI 32.5%-42.3%), 89.7% (88.6%-90.8%), 30.8% (26.7%-35.2%), and 92.1% (91.1%-93.0%), respectively. The 3 colposcopic signs were not individually sensitive in detecting CIN 3. CONCLUSION: Colposcopists using the RCI in the ALTS trial failed to detect CIN 2/3 at the levels expected.

Colposcopy↗

Digitized cervical images: problems, solutions, and potential medical impact.

OBJECTIVE: To demonstrate compression, illumination enhancement, registration, segmentation, automated classification and steganography using digitized cervical images. MATERIALS AND METHODS: The Hybrid Multi-Scale Vector Quantization algorithm developed at Texas Technological University and other automated systems were used to improve digitized cervical images. RESULTS: We demonstrated high levels of image compression, illumination enhancement, registration, automated segmentation and classification and steganography of digitized cervical images. CONCLUSIONS: Digitized cervical images can be altered to facilitate research of cervical neoplasia.

Cervix Uteri↗

Smokers at higher risk for undetected antibody for oncogenic human papillomavirus type 16 infection.

OBJECTIVE: To determine the association between tobacco smoking and serologic evidence of human papillomavirus type 16 (HPV16)-specific antibodies among HPV16 DNA-positive women. DESIGN, SETTING, AND PARTICIPANTS: Baseline health history, physical examination, and laboratory data for 205 HPV16 DNA-positive women with no prior cytologic evidence of squamous intraepithelial lesions who were enrolled subsequently in a randomized clinical trial. MAIN OUTCOME MEASURE: HPV16-L1 antibody (anti-HPV16 antibody) detected from serum using RIA or ELISA. RESULTS: Eighty-seven percent (179 of 205) of women tested positive for HPV16 DNA using cervicovaginal swabs or lavage specimens, and 26 women showed similar results using swab specimens of external genitalia alone. HPV16-infected women who reported increasingly greater levels of daily cigarette smoking were less likely to test positive for anti-HPV16 antibodies than nonsmoking women (P = 0.02). Smokers were twice as likely as nonsmokers to test negative for anti-HPV16 antibodies, even after controlling for the effects of other covariates in the analyses (adjusted odds ratio, 0.5; 95% confidence limits, 0.2-0.9). Although Papanicolaou test findings and smoking characteristics were poorly correlated (r(2) = 0.01), women who showed atypical cells of unknown significance or squamous intraepithelial lesion were twice as likely to test anti-HPV16 antibody positive as women who showed normal Papanicolaou tests (adjusted odds ratio, 2.0; 95% confidence limits, 1.1-3.7). CONCLUSION: These data suggest that smoking may influence the long-term risk for cancer by perturbing early immune responses to the virus and may increase the likelihood of persistent infection. Patient education messages should alert women to this additional risk of smoking. A clinical trial of smoking cessation should be explored as a therapeutic intervention for primary HPV16 infection.

Adolescent↗

Vaccines for preventing HPV-related anogenital infection and neoplasia.

Human papillomavirus (HPV) is a common sexually transmitted pathogen. Although most anogenital HPV infections resolve within several years, persistent infection may lead to neoplasia of the cervix, vagina, vulva, anus, and penis, and also genital warts. High-risk HPV types 16 and 18 are known to cause approximately 70% of all cervical cancers, and low-risk HPV types 6 and 11 are the main causes of genital warts. Prophylactic HPV vaccines have the potential to block the acquisition of HPV and hence subsequent development of anogenital neoplasia. Results from several clinical trials have demonstrated that the HPV L1 virus-like-particle vaccines are safe and highly immunogenic. These trials have documented a 100% vaccine efficacy in prevention of persistent HPV infection and, more important, of HPV-associated anogenital neoplasia in per-protocol analyses. Widespread vaccination of sexually naïve preadolescent children could substantially reduce the morbidity and mortality associated with anogenital malignancies. Furthermore, such a primary prevention program would also reduce healthcare costs.

Anus Diseases↗

Interobserver agreement for colposcopy quality control using digitized colposcopic images during the ALTS trial.

OBJECTIVE: To estimate interobserver agreement among colposcopy quality control reviewers viewing digitized cervical images during the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). MATERIALS AND METHODS: Three colposcopy quality control reviewers independently examined modem-transferred digitized colposcopic images from subjects examined at four clinical centers. Reviewers indicated colposcopic impression, Reid colposcopic index scores, lesion size, and the technical quality of the image. Rates of agreement were evaluated using the kappa statistic and McNemar and Bowker tests of symmetry. RESULTS: Regarding colposcopic impressions, the average weighted kappa for pairs of initial reviewers was 0.36 (95% confidence interval, 0.33-0.39). kappa scores with respect to Reid colposcopic index, cervical image quality, and lesion size ranged from 0.23 to 0.28, 0.18 to 0.27, and 0.33 to 0.42, respectively. CONCLUSIONS: Fair rates of agreement and poor to fair kappa scores among ALTS colposcopy quality control reviewers were noted for colposcopic impression, Reid colposcopic index scores, image quality, and lesion size. Great latitude exists in the interpretation of digitized cervical images. Poor image quality partially may explain these suboptimal results.

Cervix Uteri↗

Colposcopy quality control by remote review of digitized colposcopic images.

OBJECTIVE: This study was undertaken to estimate the accuracy of colposcopy quality control review of subjects' digitized colposcopic images during the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion triage study (ALTS). STUDY DESIGN: After colposcopic examination and the acquisition of 2 digitized cervical images, colposcopists recorded colposcopic diagnoses in a standardized computer database. The images were transferred by modem to colposcopy quality control reviewers for a blinded interpretation, including assessment of image quality. Reviewers' and colposcopists' diagnoses were compared with histologic diagnoses using standard contingency table methods. RESULTS: Colposcopists and reviewers underdiagnosed 16.1% and 25.3% of subjects, and overdiagnosed 44.7% and 19.8% of subjects compared with histology, respectively. The sensitivity and specificity for detecting cervical intraepithelial neoplasia 2 or greater were 35.4% versus 23.2%, P < .0001, and 89.9% versus 95.0%, P < .0001, respectively, for colposcopists and reviewers. CONCLUSION: Colposcopy quality control by review of digitized colposcopic images in clinical trials warrants further evaluation if the accuracy can be improved.

Biopsy, Needle↗

Telemedicine network telecolposcopy compared with computer-based telecolposcopy.

OBJECTIVES: To compare computer-based telecolposcopy with telemedicine network telecolposcopy. MATERIALS AND METHODS: An on-site expert and local clinician at two rural sites conducted colposcopic examinations on 264 women. Colposcopic images were captured and transmitted to two other experts at a remote location using a statewide telemedicine system and a computer and modem-based system. Sensitivity and specificity, agreement of examination adequacy and management, effects of delayed interpretations, and costs were compared for each system. RESULTS: A greater rate of satisfactory colposcopy results was reported by the telemedicine network (66.1%) compared with computer-based (43.6%) telecolposcopy (p < .0001). Greater rates of cervical biopsy (p = .005) and endocervical curettage (p = .03) were required by delayed telecolposcopy compared with immediate telecolposcopic services. There were no significant differences in sensitivity of detecting cervical neoplasia among the types of the telecolposcopy. Computer-based telecolposcopy cost 28 dollars less per patient than telemedicine network telecolposcopy. CONCLUSIONS: Computer-based telecolposcopy may be a reasonable, cost-effective adjunct to on-site colposcopy for evaluating women in medically underserved areas. Synchronous telecolposcopic examination minimizes histologic sampling and improves consultation.

Journal Article↗

Multicenter direct to vial evaluation of a liquid-based pap test.

OBJECTIVE: To estimate the efficacy of a fluid-based, thin-layer preparation (TP) compared with the conventional Pap (CP) test to detect biopsy confirmed precancerous cervical lesions. MATERIALS AND METHODS: A total of 10,226 evaluable patients at 10 separate clinical sites were screened for cervical abnormalities using the TP (ThinPrep pap test; Cytyc Corporation, Boxborough, MA). Results were compared with an historical control cohort of 20,918 patients from a similar patient population and with a similar patient profile who had received CP screening. RESULTS: The TP significantly increased the detection rate of high-grade squamous intraepithelial lesion and more severe (HSIL+) cytologic results as compared with the CP smear. Overall, the TP method yielded a 59.7% increase in the detection of HSIL+ compared with the CP smear. Overall, the TP method yielded a 59.7% increase in the detection of HSIL+ compared with the conventional method (3.9% vs. 2.4%; p < .001). There was also a significant increase in the detection of low-grade squamous intraepithelial lesions with TP (p < .01). The rates of cancer, atypical squamous cells of undetermined significance, and atypical glandular cells of undetermined significance were similar for the TP and CP groups. CONCLUSIONS: The overall cytologic detection of HSIL and low-grade squamous intraepithelial lesions with the TP method was significantly increased compared with a control group screened with the CP method. Histologic confirmation showed increased detection, not an increased false-positive cytologic interpretation.

Journal Article↗

Personal digital assistants used to document compliance of bacterial vaginosis treatment.

OBJECTIVE: The objective of this study was to estimate patient compliance with oral and vaginal metronidazole treatment of bacterial vaginosis using personal digital assistants (PDAs) and paper diaries. GOAL: The goal of this study was to assess a novel compliance documentation approach. STUDY: After each dose of intravaginal or oral metronidazole, 71 subjects recorded the time on a paper diary and answered questions on a PDA. All PDA entries were unknowingly time-date-stamped. Subjects returned for 2- and 6-week posttreatment examinations. Compliance was calculated using a repeated-measures multivariate analysis of variance (ANOVA). RESULTS: Mean patient compliance rates within the oral metronidazole group were greater with the paper diary compared with the PDA (68.3% and 50.0%, respectively, P = 0.001). The observed rate of compliance agreement for PDA versus paper diary was 69.0% (kappa = 0.4). The majority of noncompliant subjects reported they were compliant with the PDA and paper diary. CONCLUSIONS: PDAs could more accurately document true compliance rates and could be reasonable instruments to assess compliance in intravaginal antimicrobial drug or contraceptive trials.

Administration, Intravaginal↗

Psychological effects women experience before and after a colposcopic examination and primary care appointment.

OBJECTIVE.: To estimate the psychological impact, health and behavior concerns, and coping styles of women awaiting colposcopic examination compared with women awaiting a scheduled primary care appointment. MATERIALS AND METHODS.: A convenience sample of 150 women presenting for a scheduled colposcopy examination and 201 women scheduled for a primary care appointment were assessed for demographic status, depression (Center for Epidemiologic Studies/Depressed Mood Scale), anxiety, health beliefs and concerns, and coping style (Miller Behavioral Style Score). Subjects also completed a postexamination questionnaire. Mean responses were compared using Wilcoxon rank sum test. RESULTS.: Mean anxiety scores were considered "mild" and equivalent for women in the two groups. Although the colposcopy group had a significantly greater mean depression score (36.3) compared with the noncolposcopy group (33.4, p = .03, Wilcoxon test), both mean scores indicated mild depression. Women undergoing colposcopy reported greater mean scores for concern about their disease, the procedure, and potential consequences (p < .01, Wilcoxon test). CONCLUSION.: Women scheduled for colposcopy have a similar level of mild anxiety and mild depression as women scheduled for a primary care appointment. Consequently, universal, instead of selective, use of anxiolytic agents before colposcopy appears unjustified. Avoidance of triage to colposcopy for atypical squamous cells of undetermined significance Pap smear results may be unwarranted based on concerns for causing excessive anxiety. In fact, colposcopy provides substantial reassurance.

Journal Article↗

Patient acceptance of fluorescent and reflective spectroscopy as a replacement test for the pap smear.

OBJECTIVE: To determine women's acceptance of fluorescent and reflective spectroscopy (FRS) as a potential replacement test for the Pap smear. MATERIALS AND METHODS: Women scheduled for a colposcopic examination, or a colposcopic and FRS examination, completed a 22-item questionnaire that included demographic data, medical history, and preference-type questions. Data were compared using chi and Wilcoxon's rank sum tests. RESULTS: Women considered accuracy, comfort, and quick results to be the most important characteristics for new cervical cancer tests. Immediate test results were preferred strongly by both groups (control, 84.5%; scanned, 88.6%). Provided FRS was more accurate than the Pap smear, most women (control, 74.7%; scanned, 68.2%) would rather have FRS if it cost the same as a Pap smear. CONCLUSIONS: Women consider accuracy, comfort, and time critical issues with respect to FRS used as a primary screening test. Acceptance of this new technology will be facilitated by designing equipment accordingly to satisfy the concerns of women.

Journal Article↗

Women's responses to cervical interrogation by fluorescent and reflective spectroscopy.

OBJECTIVE: To determine women's responses to cervical interrogation by fluorescent and reflective spectroscopy (FRS). MATERIALS AND METHODS: A convenience sample of women scheduled for a colposcopic examination was interrogated by a cervical FRS system. Thereafter, women completed a 24-item questionnaire that assessed their responses to the spectroscopic test. Likert-scale responses were compared among subgroups using the chi test for trend. RESULTS: Most women favored FRS used for locating (97.7%; 170/174) and selectively sampling (96.6%; 168/174) cervical neoplasia. Fewer women (81.0%; 141/174) wanted FRS to replace the Pap smear. Most women were neither nervous (73.6%; 128/174) nor bothered (89.1%; 155/174) by the extra time for the FRS assessment. Women's acceptance was substantiated by 84.9% (146/174) and 90.8% (157/173) wanting their doctor to have and insurance company to pay for FRS, respectively. CONCLUSIONS: Use of FRS as a colposcopic adjunct was supported very favorably by women. Fewer women supported FRS replacing Pap smears. These high rates of approval by women should help the implementation of FRS technology.

Journal Article↗

Liquid-based pap smears as a source of RNA for gene expression analysis.

The Papanicolaou smear has contributed to a decrease in cervical cancer rates in populations that receive regular screening. However, treatment of women with mildly abnormal cells is problematic because the majority of these women do not develop neoplasia. Thus, new techniques for identification of truly precancerous cells are needed. Characterization of cellular gene expression patterns is now possible through microarray techniques that survey the expression of large numbers of genes simultaneously. Here we have assessed the feasibility of combining new microscopic and molecular technologies to determine gene expression patterns in cervical intraepithelial neoplasia grade 3 cells recovered from liquid cytology-based Papanicolaou smear slides. Laser capture microdissection was used to retrieve cervical cells from ThinPrep prepared slides. The quality of RNA recovered from these cells proved suitable for reverse transcription polymerase chain reaction and for T7 RNA polymerase-based linear amplification of messenger RNA. We developed an optimized RNA amplification protocol that permitted microarray gene expression profiling in samples of as few as 20 cervical cells. This approach combining laser capture microdissection, linear RNA amplification, and microarray gene expression analysis will enable comparison of gene expression patterns between cytologically abnormal and normal cells taken from a single slide and may assist in the differential diagnosis of histologically difficult cases.

Biomarkers↗