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Michele Follen

Publications and source records attributed to Michele Follen.

At least 37 records · Page 2Linked to original sources
PubMed2005

Knowledge of cervical dysplasia and human papillomavirus among women seen in a colposcopy clinic.

OBJECTIVE: This study was undertaken to evaluate knowledge of cervical dysplasia and human papillomavirus (HPV) among women seen in a colposcopy clinic. STUDY DESIGN: Demographics, knowledge, and psychological distress were assessed in structured interviews with 175 women before, during, and after colposcopy. RESULTS: Respondents had low knowledge scores before and after colposcopy; however, their overall knowledge improved slightly (P = 0.013) following the exam. When responses were examined by question, respondents demonstrated a significant increase of correct answers to only one question: Does dysplasia, or precancerous cells on the cervix, always go away without treatment? Pre-exam knowledge was positively associated with educational level and was lower among Hispanics and patients recruited at the clinic. Post-exam knowledge was positively associated with pre-exam knowledge and educational level. CONCLUSION: Routine clinical education during colposcopy can improve patients' understanding of cervical cancer; however, the low level of knowledge that persisted after colposcopy is a cause for concern.

Adolescent↗
PubMed2005

Confocal microscopy: imaging cervical precancerous lesions.

OBJECTIVES: We explore the clinical potential of reflectance and fluorescence confocal microscopy to image the morphologic and biochemical changes associated with precancer, in order to aid in the detection and diagnosis of cervical dysplasia. METHODS: Cervical epithelial tissue samples imaged ex vivo or in vivo were obtained from M. D. Anderson Cancer Center and Lyndon B. Johnson Hospital in Houston, Texas. Confocal reflectance microscopy was used to image ex vivo cervical biopsies and in vivo cervical tissue. Confocal fluorescence microscopy was used to image ex vivo cervical tissue slices. RESULTS: We present reflectance and fluorescence confocal images of cervical tissue demonstrating the ability to differentiate between normal and abnormal cervical tissue. CONCLUSIONS: We believe that there is significant clinical potential for confocal microscopy to provide a sensitive and specific method for cervical precancer detection.

Biopsy↗
PubMed2005

Participant recruitment and motivation for participation in optical technology for cervical cancer screening research trials.

In order to improve recruitment for cervical cancer screening trials, it is necessary to analyze the effectiveness of recruitment strategies used in current trials. A trial to test optical spectroscopy for the diagnosis of cervical neoplasia recruited 1000 women from the community; the trial evaluated the emerging technology against Pap smears and colposcopically directed biopsies for cervical dysplasia. We have examined women's reasons for participating as well as the effectiveness and efficiency for each recruitment strategy. Reasons for participation were identified and compared between trials. The recruitment method that resulted in the most contacts was newspaper reportorial coverage and advertising, followed by family and friends, then television news coverage. The most cost-effective method for finding eligible women who attend the research appointment is word of mouth from a family member or friend. Recommendations are given for maximizing the efficiency of recruitment for cervical cancer screening trials.

Clinical Trials as Topic↗
PubMed2005

Sources of scattering in cervical tissue: determination of the scattering coefficient by confocal microscopy.

Most models of light propagation through tissue assume that the scattering properties of various tissue layers are the same. We present evidence that the scattering coefficient of cervical epithelium varies by a factor of 3 within the epithelium owing to variations in nuclear density and to the presence of keratin. We estimated the scattering coefficient from regions of normal and precancerous cervical epithelium by fitting reflectance measurements from confocal images to an exponential function of depth based on Beer's law of attenuation. The results suggest that the normal cervix is characterized by highly variable scattering in the superficial epithelium, low scattering in the intermediate epithelium, and high scattering in the basal and stromal regions. In high-grade dysplasia, high scattering from high-density nuclei is observed throughout the entire epithelium.

Algorithms↗
PubMed2005

In vivo fiber-optic confocal reflectance microscope with an injection-molded plastic miniature objective lens.

For in vivo optical diagnostic technologies to be distributed to the developed and developing worlds, optical imaging systems must be constructed of inexpensive components. We present a fiber-optic confocal reflectance microscope with a cost-effective injection-molded plastic miniature objective lens for in vivo imaging of human tissues in near real time. The measured lateral resolution is less than 2.2 microm, and the measured axial resolution is 10 microm. Confocal images of ex vivo cervical tissue biopsies and in vivo human lip taken at 15 frames/s demonstrate the microscope's capability of imaging cell morphology and tissue architecture.

Cervix Uteri↗
PubMed2005

Results of a phase II double-blinded randomized clinical trial of difluoromethylornithine for cervical intraepithelial neoplasia grades 2 to 3.

PURPOSE: Our purpose was to conduct a double-blinded randomized trial of difluoromethylornithine (DFMO) at 0.125, 0.5 gm/m2, versus placebo in the treatment of cervical intraepithelial neoplasia (CIN) grades 2 to 3. A promising phase I study has shown histopathologic responses at these dose levels. EXPERIMENTAL DESIGN: Patients with histopathologically confirmed CIN 2-3 lesions were recruited from a colposcopy clinic and underwent Papanicolaou testing, human papillomavirus testing, and colpophotography. They took oral contraception and DFMO or placebo elixir for 28 days and filled out the National Cancer Institute common toxicity calendars. They returned for follow-up and a repeat Papanicolaou smear, colpophotograph, and loop excision of the cervix. RESULTS: There were no statistically significant differences among the arms in histopathologic response. This could no be explained by any biases in risk factors. The prominent toxicities were diarrhea, dizziness, nausea, and headaches. There were no differences in the toxicities among arms. The Papanicolaou smear was a poor biomarker of response and correlated poorly with the histopathology. CONCLUSIONS: DFMO is no active at 0.125 and 0.5 gm/m2 for 28 days when given orally in CIN 2-3. Higher oral doses or longer administration is necessary, supporting data from breast trials. Alternatively, a trial of topical DFMO might merit attention as activity has been noted in trials of actinic keratoses.

Adolescent↗
PubMed2005

Optical coherence tomography: a pilot study of a new imaging technique for noninvasive examination of cervical tissue.

OBJECTIVE: Optical coherence tomography (OCT) is a novel noninvasive technique that can map subsurface tissue structure with a resolution of 10 to 20 mum. The objective of this study was to determine whether an OCT imaging system could be used clinically in vivo to image and distinguish features of normal and abnormal cervical tissue. STUDY DESIGN: Cervical OCT images and biopsy specimens were obtained from consenting volunteers. Images were analyzed quantitatively for intensity of backscattered light from the epithelia and for rates of signal decay of signal over the depth of epithelia (slope). Patients were stratified by menopausal status, and parameters were compared in normal and abnormal cervical samples, as diagnosed by routine histopathologic techniques. RESULTS: Average epithelial intensities were significantly stronger in the abnormal tissue than in the normal tissue of premenopausal women (P<.0024), but were stronger in the normal tissue of postmenopausal women (P<.062). No significant differences in signal decay rate were detected. CONCLUSION: OCT images, which contain information about epithelial and stromal structure, can be clinically obtained. Image features of normal and abnormal cervical epithelium differ significantly.

Adult↗
PubMed2005

Human papillomavirus type 16 E2 and E6/E7 variants.

OBJECTIVES: Polymorphisms in human papillomavirus (HPV) type 16 have been shown to be related to geographic areas and are broadly classified as European (E), African (Af), Asian (As), or Asian-American (AA). Certain variants have been reported as being more likely to cause cervical disease; our objectives were to identify new HPV16 polymorphisms, to determine the linkage of the E2 and E6/E7 regions and to determine the minimum sequence necessary to classify variants. METHODS: We sequenced the complete E2, E6, and E7 regions in all HPV16-positive cervical samples identified in a case-control study of pre-invasive cervical disease. RESULTS: In the 100 samples analyzed, only one new polymorphism was identified, a synonymous change, T3205A, in region E2. The frequency distribution of variants in the sample set was 37 European prototypes and 27 E-G350, 16 AA, 5 Af1, 2 Af2, 8 E-C109G, 3 E-G131G, and 2 As. As shown by others, region E7 varied much less than E6 and E2. CONCLUSIONS: In each case, E2 changes were linked to the expected E6/E7 changes, and there was no evidence for recombination. The linkage between E2 and E6/E7 allows variant classification to be based on a short E6 sequence (nt 109-350).

Base Sequence↗
PubMed2005

See-and-treat strategy for diagnosis and management of cervical squamous intraepithelial lesions.

In a see-and-treat protocol, patients referred for colposcopy because of an abnormal Pap smear in cervical-cancer screening can be treated by loop excision, without biopsy, during one visit to the clinic. However, overtreatment in the see-and-treat strategy has been reported to be 1.2-83.3% for low-grade squamous intraepithelial lesions (SIL) and to be 13.3-83.3% for high-grade SIL. Range of overtreatment narrowed to 4.0-23.5% for those with normal pathology and to 18.0-29.4% for those with normal or low-grade pathology when calculation of overtreatment was restricted to patients diagnosed with high-grade SIL on colposcopy and referral Pap smear. Most common treatment complications are bleeding and infection. Nonetheless, the strategy has become accepted internationally: low costs, decreased patient anxiety, and increased compliance make it appealing, especially in settings with limited health resources, and for patients at risk of not being treated in a timely manner or of not returning for a second appointment. Mathematical modelling may give information about the appropriateness and usefulness of this treatment while the results of long-term clinical trials are awaited.

Clinical Trials as Topic↗
PubMed2005

Correlation of human papillomavirus type 16 and human papillomavirus type 18 e7 messenger RNA levels with degree of cervical dysplasia.

Infection with certain types of human papillomavirus (HPV) is a necessary event in the development of cervical carcinoma; however, not all women who become infected with HPV will progress to cancer. Much is known about the molecular influence of HPV E6 and E7 proteins on the malignant transformation. Little is known about the additional factors needed to drive the process. Quantitative real-time PCR was used to quantitate mRNA expression of the E7 gene in women exhibiting normal epithelium, low-grade squamous intraepithelial lesions (LSIL), and high-grade squamous intraepithelial lesions (HSIL). Prevalence of mRNA transcripts was lower among normal women (27%) than for women with LSIL (40%) and HSIL (37%). Mean levels ranged from 2.0 (ln scale per 20 ng cDNA) among normal women to 4.2 among those with HSIL, with a significant trend (P=0.008). This trend was only significant for HPV 18 transcripts if separately analyzed by HPV type. The transcriptional activity of HPV 18 is higher than that of HPV 16 and increases with increasing level of dysplasia. This is in concert with the findings of other studies, and reinforces the notion that HPV 18 is a more aggressive viral type. Real-time PCR of viral transcripts could provide a more efficient method to analyze the oncogenic potential within cells from a cervical swab, thus providing a way to better screen women who may progress to higher grade lesions or invasive carcinoma from those who will spontaneously regress.

Adult↗
PubMed2005

Optical technologies for cervical neoplasia: update of an NCI program project grant.

Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer mortality in women in developing countries. In the United States, over $6 billion is spent annually in the evaluation and treatment of low-grade lesions, many of which do not develop into full-blown cancer. In developing countries, however, the chief concern is that cervical cancer goes undetected because of the cost of testing and the lack of resources and trained personnel to screen and diagnose the disease. The goal of the National Cancer Institute Program Project Grant CA82710 is to assess the emerging technologies of fluorescence and reflectance spectroscopy and quantitative cytology and histopathology for the diagnosis of cervical neoplasia. All of these technologies should decrease mortality, morbidity, and the cost of treating cervical cancer.

Computational Biology↗
PubMed2004

Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus.

BACKGROUND: As part of a project to evaluate emerging optical technologies for cervical neoplasia, our group is performing quantitative histopathological analyses of biopsy specimens from 1,190 patients. Objectives in the interim analysis are (a) quantitatively assessing progression of the neoplastic process of cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesions (SIL), (b) detecting malignancy-associated changes (MACs), and (c) phenotypically measuring human papillomavirus (HPV) detected by DNA testing. METHODS: The diagnostic region of interest (ROI) from immediately adjacent sections were imaged, and the basal lamina and surface of the superficial layer were delimited. Nonoverlapping quantitatively stained nuclei were selected from 1,190 samples with histopathological characteristics of normal (929), koilocytosis (130), CIN 1 (40), CIN 2 (23), and CIN 3/carcinoma in situ (CIS) (68). A fully automatic procedure located and recorded the center of every nucleus in the region of interest (ROI). We used linear discriminant analysis to assess the changes between normal and CIN 3/CIS. RESULTS: Scores computed from the cell-by cell features and the clinical grade of CIN/SIL were highly correlated, as were those of the architectural features and the clinical grade of CIN/SIL. We found even higher correlations between a combination of cell-by-cell and architectural scores, and clinical grade. Using these scores, we found MACs in the normal biopsy specimens from patients with high-grade CIN/SIL. Furthermore, the same scores correlated with the molecular detection of HPV. CONCLUSIONS: Quantitative histopathology can be used in large clinical trials as an objective and reproducible measure of CIN/SIL. Detectable phenotypic changes correlate well with CIN/SIL neoplastic progression. It can also be used to infer the presence of CIN/SIL (MACs) and molecular changes associated with increased risk of cancer development (high-risk HPV).

DNA, Viral↗
PubMed2004

The effects of repeated spectroscopic pressure measurements on fluorescence intensity in the cervix.

OBJECTIVE: Fluorescence spectroscopy is a promising technology for the detection of cervical squamous intraepithelial lesions (SILs). In this study we took repeated measures in the cervix to determine whether the order of measurement produces changes in fluorescence intensity and whether there are differences in variation due to pressure. METHODS: A pressure sensitive fiber-optic probe to measure fluorescence spectra was calibrated at light, medium, and firm levels (0.2, 0.4, 0.6 N). Measurements were made 3 times at each of 2 sites in the patient's cervix. Spectroscopic data were preprocessed and analyzed to compare order of pressure and intensity variability as a function of pressure on measurements. RESULTS: Four providers took 3 measurements from 2 sites each in 18 patients, yielding 108 measurements. After corrections for multiple comparisons, neither the order of probe pressure nor the variability of probe pressure significantly affected variations in fluorescence intensity. CONCLUSION: This study shows that the probe pressure variability is probably not an issue for these devices.

Adult↗
PubMed2004

Quantitative histopathology and chromosome 9 polysomy in a clinical trial of 4-HPR.

OBJECTIVE: This trial examined the use of 4-hydroxyphenyl-retinamide (4-HPR), demonstrated to be a potent inhibitor of carcinogenesis in vitro and in animal models, in patients with cervical intraepithelial neoplasia (CIN) grades 2 to 3. Quantitative pathology and chromosome 9 polysomy were used to understand the biology and quantify the clinical histopathologic changes observed. METHODS: Patients were randomized to 4-HPR or placebo for 6 months and followed for six more months. Cervical biopsies were obtained at baseline, 6 months, and 12 months; the biopsies were read blinded three times by the study pathologist. Feulgen-stained sections were also obtained and analyzed using computer-assisted image cytometry. Chromosome 9 polysomy was performed on tissue slices using in situ hybridization and measured quantitatively. Statistical analyses were carried out in S-Plus (Insightful Corporation, Seattle, WA) and R. RESULTS: The interim analysis, planned for 40 patients, was carried out on 39. The 6- and 12-month analyses showed a statistically significant difference between the two study arms. When code was broken, the 4-HPR-treatment arm was found to have fared less well than placebo. Analyses of Feulgen-stained sections provided a quantitative measure of the increase of DNA content and texture features. Chromosome 9 polysomy was also measured using image analysis. The changes observed were consistent with those of cells displaying cancerous changes, indicating a lack of response. CONCLUSION: 4-HPR is not active at 200 mg/day. The interim analysis was helpful in directing the study; and, in this case, ending it. The intermediate endpoint biomarkers of quantitative histomorphometry and chromosome 9 polysomy yielded quantitative and repeatable results consistent with the findings of the clinical pathologist.

Anticarcinogenic Agents↗
PubMed2004

Distress after an abnormal Pap smear result: scale development and psychometric validation.

BACKGROUND: Psychological distress is severe in women who receive a report of abnormal findings on Pap smear, and may be one reason 10-61% of such women fail to undergo follow-up testing. METHODS: Using the 14-question Psychosocial Effects of Abnormal Pap Smears Questionnaire (PEAPS-Q) as a basis, we developed the 23-question Cervical Dysplasia Distress Questionnaire (CDDQ), testing its internal consistency and validity with 661 women undergoing colposcopy after an abnormal Pap smear finding in a three-phase analysis. RESULTS: Items were divided into two sets and factor analyzed separately: one addressed distress during medical procedures, and the other concerned perceived consequences of an abnormal Pap smear. The medical procedures items yielded two factors: embarrassment regarding the procedures and discomfort/tension with the procedures. Factor analysis of the second set also resulted in two factors: concern about sexual and reproductive issues and concern about health consequences. Subscales created from items loading highly on each factor had high internal consistency (alpha ranged from 0.76 to 0.90) and demonstrated good concurrent validity with other psychometrically validated measures of distress. CONCLUSIONS: The CDDQ is a reliable and valid questionnaire for measuring multiple domains of distress unique to women who test positive on a cervical cancer screening test.

Adult↗
PubMed2004

Depressed type 1 cytokine synthesis by superantigen-activated CD4+ T cells of women with human papillomavirus-related high-grade squamous intraepithelial lesions.

Carcinoma of the cervix is causally related to infection with the human papillomavirus (HPV), and T cells play a pivotal role in the immune response of the host to rid itself of HPV infection. Therefore, we assessed the T-cell function of women with HPV-related cervical neoplasia against a superantigen, Staphylococcus enterotoxin B (SEB). Each woman provided a cervical brush specimen for HPV DNA testing and Papanicolaou (Pap) smears for the staging of cervical lesions. They also provided a blood specimen for determination of the ability of CD4(+) T and CD8(+) T cells to synthesize Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and Th2 (IL-10) cytokines in response to activation with SEB. Compared with control subjects with self-attested negative Pap smears, women with high-grade squamous intraepithelial lesions (HSIL) had significantly lower percentages of activated CD4(+) T cells that produced IL-2 (P = 0.045), IFN-gamma (P = 0.040), and TNF-alpha (P = 0.015) and a significantly lower percentage of activated CD8(+) T cells that produced IL-2 (P < 0.01). These data indicate that women with HPV-related cervical HSIL show a decrease in Th1 cytokine production by activated CD4(+) T cells and suggested that compromised T-helper functions may negatively impact the function of cytotoxic CD8(+) T cells.

Antigens, Bacterial↗
PubMed2004

Quantitative histopathological analysis of cervical intra-epithelial neoplasia sections: methodological issues.

OBJECTIVES: As part a Program Project to evaluate emerging optical technologies for cervical neoplasia, our group is performing quantitative histopathological analysis of biopsies from 1,800 patients. Several methodological issues have arisen with respect to this analysis: (1) Finding the most efficient way to compensate for staining intensity variation with out losing diagnostic information; (2) Assessing the inter- and intra-observer variability of the semi-interactive data collection; and (3) the use of non-overlapping cells from the intermediate layer only. METHODS: Non-overlapping quantitatively stained nuclei were selected from 280 samples with histopathological characteristics of normal (199), koilocytosis (37), CIN 1 (18), CIN 2 (10) and CIN 3 (16). Linear discriminant analysis was used to assess the diagnostic information in three different feature sets to evaluate and compare staining intensity normalization methods. Selected feature values and summary scores were used to evaluate intra- and inter-observer variability. RESULTS: The features normalized by the internal subset of the imaged cells had the same discriminatory power as those normalized by the control cells and by both normalization methods seem to have additional discriminatory power over the set of features which do not require normalization. The use of the internal subset decreased the image acquisition time by approximately 50% at each center, respectively. The intra- and inter-observer variability was of a similar size. Good performance was obtained by measuring the intermediate layer only. CONCLUSION: The use of intensity normalization from a subset of the imaged non-overlapping intermediate layer cells works as well as or better than any of the other methods tested and provides a significant timesaving. Our intra- and inter-observer variability do not seem to affect the diagnostic power of the data. Although this must be tested in a larger data set, the use of intermediate layer cells only may be acceptable when using quantitative histopathology.

Cell Nucleus↗