Biomedical subjects

M F Mitchell

Publications and source records attributed to M F Mitchell.

At least 37 records · Page 2Linked to original sources

PubMed1998

A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix.

OBJECTIVE: To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). METHODS: Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using chi2 statistics, logistic regression analysis, and the Cox proportional hazards model. RESULTS: Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6-37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). CONCLUSION: The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above.

Adolescent↗

PubMed1997

Involvement of reactive oxygen species in N-(4-hydroxyphenyl)retinamide-induced apoptosis in cervical carcinoma cells.

BACKGROUND: The inhibitory effects of N-(4-hydroxyphenyl)retinamide (4HPR) on tumorigenesis and tumor growth may result from its ability to induce apoptosis (programmed cell death). Since antioxidants inhibit 4HPR-induced apoptosis, experiments were planned to determine whether the levels of reactive oxygen species increase in cells undergoing apoptosis after exposure to 4HPR. METHODS: Cells of the human cervical carcinoma cell line C33A and normal human cervical epithelial cells were treated with 4HPR and analyzed for survival, induction of apoptosis, generation of reactive oxygen species, and expression of the apoptosis-related proteins Bcl-2 and Bax. RESULTS: Treatment with 4HPR decreased C33A cell number by inducing apoptosis in a time- and dose-dependent fashion. DNA fragmentation typical of apoptosis was observed in cells exposed to 4HPR at concentrations of 3 microM or higher for 6-24 hours. The generation of reactive oxygen species was enhanced by 1.85-fold to 4.5-fold after a 1.5-hour treatment with 0.4-10 microM 4HPR. Pyrrolidine dithiocarbamate, an oxygen radical scavenger, suppressed the rate of generation of reactive oxygen species and inhibited 4HPR-induced apoptosis. 4HPR failed to modulate cellular levels of the Bcl-2 and Bax proteins. N-(4-Methoxyphenyl)retinamide, the major 4HPR metabolite, and several other retinoids that bind to nuclear retinoic acid receptors or retinoid X receptors failed to enhance the generation of reactive oxygen species and to induce apoptosis. 4HPR was much less effective in generating reactive oxygen species and in inducing apoptosis in normal human cervical epithelial cells than in C33A cervical carcinoma cells. CONCLUSIONS: Enhancement of the generation of reactive oxygen species may be involved in apoptotic pathway induction by 4HPR.

Antioxidants↗

PubMed1997

Adenocarcinoma of the cervix. Expression and clinical significance of estrogen and progesterone receptors.

BACKGROUND: Although hormone receptor status is an important prognostic indicator in adenocarcinoma of the breast and the endometrium, few studies have investigated the expression and clinical significance of estrogen receptor (ER) and progesterone receptor (PgR) in adenocarcinoma of the cervix. METHODS: ER and PgR expression were determined using an immunohistochemical method in 84 cervical adenocarcinomas. Clinical features and outcome were determined by chart review. RESULTS: ER was identified in 17 of the 84 cases (20%). ER positivity was most frequently detected in mucinous adenocarcinoma of the endocervical type (in 11 of 48 cases) and endometrioid adenocarcinoma (in 4 of 10 cases). PgR was identified in 23 of the 84 cases (27%). PgR positivity was also most frequently detected in mucinous adenocarcinoma of the endocervical type (in 15 of 48 cases) and endometrioid adenocarcinoma (in 6 of 10 cases). Mucinous adenocarcinoma of the intestinal type (five cases), glassy cell carcinoma (two cases), and clear cell adenocarcinoma (two cases) were uniformly negative for both ER and PgR. No association was detected between International Federation of Gynecology and Obstetrics stage and receptor status, but there was a somewhat lower frequency of ER positivity in poorly differentiated tumors (P = 0.07). No association was detected between PgR status and disease free survival. Similarly, no association between ER status and overall survival was observed. Although ER positive tumors may be associated with longer disease free survival than ER negative tumors, this difference did not reach statistical significance in this study (P = 0.06). CONCLUSIONS: ER and PgR positivity were found in 20% and 27%, respectively, of primary cervical adenocarcinomas. However, receptor status was not significantly associated with either overall survival or disease free survival.

Adenocarcinoma↗

PubMed1997

Safety analysis: relative risks of ultraviolet exposure from fluorescence spectroscopy and colposcopy are comparable.

Fluorescence spectroscopy is a promising tool for use in the diagnosis of disease in human tissue. However, few published reports have evaluated the safety of this technique, despite the fact that many spectroscopic systems use UV illumination. This study determined the relative risk associated with light exposure from spectroscopic systems compared with the traditional light sources that are used to illuminate tissue and direct biopsies. We compared spectroscopic detection systems for the cervix to the colposcope, a low-power microscope routinely used to illuminate the cervix, which does not cause any known photochemical damage. We measured the average spectral irradiance (W/[cm2nm]) and the average tissue exposure time during a diagnostic colposcopy examination. To quantify the relative risks, we multiplied illumination spectra by several action spectra from the literature and compared the areas under the curves corresponding to each procedure. The risk associated with the average power colposcope served as our basis for comparison. We conclude that the risks of illumination using spectroscopic systems are lower than or comparable to those already encountered in routine diagnostic procedures such as colposcopy with an average power colposcope. Spectroscopic examination can be associated with a somewhat higher risk than a colposcopy with the lowest power colposcope or a shorter than average colposcopy. The analysis presented can be repeated to estimate the magnitude of risks associated with other spectroscopic diagnostic devices.

Colposcopy↗

PubMed1997

Progressive dysregulation of proliferation during cervical carcinogenesis as measured by MPM-2 antibody staining.

To better characterize the amount and location of loss of proliferation control during cervical carcinogenesis, 44 cervical cone biopsy specimens containing various grades of premalignant and malignant lesions and 12 normal cervix specimens were immunohistochemically examined using MPM-2. This antibody recognizes a phosphorylated epitope on a group of proteins that are preferentially phosphorylated at mitosis. The spatial organization of mitotic figures was determined using a computer-assisted image analysis system. The mitotic figure frequencies/unit of epithelial area were found to increase as the histological type progressed; the numbers of mitoses/square millimeter was 1.7 +/- 0.5 (mean +/- SE) for control normal epithelium (n = 12), 3.1 +/- 1.7 for normal epithelium adjacent to cervical intraepithelial neoplasia (CIN) and cancer (n = 28), 7.9 +/- 1.3 for CIN1 (n = 24), 75.8 +/- 16.3 for CIN2 (n = 11), 127.2 +/- 9.7 for CIN3 (n = 22), 196.9 +/- 33.2 for carcinoma in situ (n = 9), and 156.2 +/- 31.0 for cervical carcinoma (n = 8). The MPM-2 index was higher in high-risk premalignant lesions (i.e., those adjacent to areas of high-grade CIN and carcinoma) than it was in lower risk premalignant lesions (i.e., those with no adjacent higher grade CIN or cervical cancer), even if they exhibited the same histological grade. Moreover, the mean relative distance of the mitotic cells from the basement membrane (i.e., the distance from the basal layer to the surface) also increased as the histological grade progressed. These results suggest that proliferation becomes sequentially dysregulated both quantitatively and spatially during cervical carcinogenesis and that the MPM-2 antibody might be useful as a proliferation biomarker.

Antibodies, Monoclonal↗

PubMed1997

DNA image cytometric measurement as a surrogate end point biomarker in a phase I trial of alpha-difluoromethylornithine for cervical intraepithelial neoplasia.

Cervical intraepithelial neoplasia grade 3 (CIN 3) is considered a high-risk precursor of invasive cervical cancer. alpha-Difluoromethylornithine (DFMO) is a promising antiproliferative chemopreventive agent. The purpose of this study was to evaluate image cytometric measurement of nuclear DNA (ICM-DNA) as a surrogate end point biomarker (SEB) in a Phase I trial of DFMO for CIN. Thirty patients with CIN 3 were treated with DFMO at five doses, ranging from 0.0625 to 1.0 g/m2/day, for 1 month. Half of the patients had histological responses. Twenty-five pre- and posttreatment cervical biopsy specimens (from 11 responders and 14 nonresponders) were available for this analysis. ICM-DNA was performed on 4-micron sections cut from formalin-fixed tissue blocks and stained with a thionin-SO2 Feulgen reaction. ICM-DNAs for each case were expressed as normalized measurements (against the nuclear modal absorbance of lymphocytes) of the absorbance of each cell of interest and were presented in bar histograms. The mean normalized summed absorbance (sigma ODn) was obtained as a mean histogram of the cell population of interest. Nineteen (76%) of 25 patients had a significant decrease in sigma ODn after DFMO treatment. Posttreatment values were significantly lower than pretreatment values in a paired analysis, and responders had significantly lower values than nonresponders. Analyses of different ICM-DNA references, including percentile values of sigma ODn distribution, DNA malignancy grade, and 5c exceeding rate, showed a decrease of mean sigma ODn during DFMO treatment. In addition, the summed posttreatment sigma ODn histograms also showed progressively shorter right shoulders compared with pretreatment histograms in both responders and nonresponders. We concluded that the modulation of sigma ODn reflected the chemoprevention effect of DFMO even before morphological changes appeared, and thus, ICM-DNA may be useful as a SEB in chemoprevention trials of DFMO. Additional reasons for using ICM-DNA as a SEB are the relative simplicity of its use, the high accuracy of the results, the low cost of the reagents, the ability to use small tissue samples, and the objectivity and reproducibility of the procedure.

Adult↗

PubMed1997

Polyamine measurements in the uterine cervix.

Cervical cancer remains a significant health problem. New strategies based on the molecular aspects of cervical carcinogenesis are needed. Chemoprevention represents a novel strategy for cervical cancer prevention. Our group plans phase I and II trials using alpha-difluoromethylornithine, a suicide inhibitor of ornithine decarboxylase and potent antiproliferative chemopreventive agent. We conducted a study to identify which polyamines in tissue could best serve as surrogate endpoint biomarkers for future trials. Thirty patients with biopsy-proven cervical intraepithelial neoplasia grade 3 underwent colposcopically directed biopsies of normal and abnormal areas of the uterine cervix for analysis of polyamine synthesis biomarkers. Statistically significant differences were found in the ornithine decarboxylase value and the spermidine:spermine ratio between normal and abnormal areas of the cervix. In general, the ranges in measurements varied widely. Differences in polyamine synthesis biomarkers between colposcopically normal and abnormal areas can be demonstrated. However, studies using polyamine synthesis biomarkers in the cervix would require large numbers of patients to achieve significance.

Cervix Uteri↗

PubMed1996

Sexual adjustment of patients undergoing gracilis myocutaneous flap vaginal reconstruction in conjunction with pelvic exenteration.

BACKGROUND: Although the technique for gracilis myocutaneous vaginal reconstruction was first described in the mid-1970s and has been used in conjunction with pelvic exenteration since that time, there is little available information regarding sexual adjustment after such a procedure. The purpose of this study was to assess the sexual adjustment of women who underwent pelvic exenteration and gracilis myocutaneous vaginal reconstruction at the study institution. METHODS: In a prospective study design, 95 patients were identified who underwent pelvic exenteration and gracilis myocutaneous vaginal reconstruction at the study institution from 1977 through 1989 and a convenience sample was selected of 44 patients who completed a modified version of the Sexual Adjustment Questionnaire (SAQ) when they returned to the gynecologic oncology outpatient clinic for routine follow-up care. A vaginal assessment was also performed by the attending physician. RESULTS: Twenty-one of 40 patients (52.5%) completing the questionnaire reported not resuming sexual activity after surgery; 19 patients reported sexual activity between 1.5 months to 12 years postoperatively. Of the patients who resumed sexual activity, 84% did so within 1 year of surgery. The most common problems noted by patients in adjusting to sexual activity after surgery were self-consciousness about the urostomy or colostomy and being seen in the nude by their partner, vaginal dryness, and vaginal discharge. The mean rank of preexenteration SAQ scores was 66.4, and the mean rank of postexenteration scores was 48.7 (P < 0.0001), demonstrating that sexual adjustment after exenteration was significantly poorer than before the surgery. On the basis of data gathered from a vaginal assessment form, 31 of 44 patients (70.4%) were judged to have a potentially functional neovagina. CONCLUSIONS: Based on the findings of this questionnaire study, sexual adjustment is often significantly impaired in women after pelvic exenteration and gracilis myocutaneous vaginal reconstruction. Future modifications in surgical technique, more realistic patient counseling and aggressive postoperative support will hopefully minimize such problems.

Adaptation, Psychological↗

PubMed1996

Adenovirus-mediated transfer of a wild-type p53 gene and induction of apoptosis in cervical cancer.

In most cervical cancers, the function of p53 is down regulated. To explore the potential use of p53 in gene therapy for cervical cancer, we introduced wild-type p53 into cervical cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p53, and analyzed its effects on cell and tumor growth. The transduction efficiencies of all cell lines were 100% at a multiplicity of infection of 100 or greater. The p53 protein was detected in Ad5CMV-p53-infected cells. Protein expression peaked at day 3 after infection and lasted 15 days. The Ad5CMV-p53-infected cells underwent apoptosis, and cell growth was greatly suppressed. The Ad5CMV-p53 treatment significantly reduced the volumes of established s.c. tumors in vivo. These results indicate that transfection of cervical cancer cells with the wild-type p53 gene via Ad5CMV-p53 is a potential novel approach to the therapy of cervical cancer.

Adenoviridae↗

PubMed1996

Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo.

BACKGROUND AND OBJECTIVE: A general multivariate statistical algorithm has been developed to analyze the diagnostic content of cervical tissue fluorescence spectra acquired in vivo. MATERIALS AND METHODS: The primary steps of the algorithm are to: (1) preprocess the data to reduce inter-patient and intra-patient variation of tissue spectra within a diagnostic category, without a priori information, (2) dimensionally reduce the preprocessed fluorescence emission spectrum with minimal information loss and use it to select the minimum number of the original emission variables of the fluorescence spectrum required to achieve classification with negligible decrease in predictive ability, and (3) assign a posterior probability to the diagnosis of each sample, so that samples with relative uncertain diagnosis can be reevaluated by a clinician. The algorithm was tested retrospectively and prospectively on cervical tissue spectra acquired from 476 sites from 92 patients at 337 nm excitation. RESULTS: The algorithm based on the entire fluorescence spectrum differentiates squamous intraepithelial lesions (SILs) from normal squamous epithelia and inflammation with an average sensitivity and specificity of 88% +/- 1.4 and 70% +/- 1, respectively. The average sensitivity and specificity of the identical algorithm based on intensity selected at only two emission wavelengths is 88% +/- 1.4 and 71% +/- 1.4, respectively. CONCLUSION: The multivariate statistical algorithm based on both types of spectral inputs at 337 nm excitation has a similar sensitivity and significantly improved specificity relative to colposcopy in expert hands.

Algorithms↗

PubMed1996

Spectroscopic diagnosis of cervical intraepithelial neoplasia (CIN) in vivo using laser-induced fluorescence spectra at multiple excitation wavelengths.

BACKGROUND AND OBJECTIVE: The diagnostic contribution of cervical tissue fluorescence spectra acquired in vivo at 380 and 460 nm excitation were analyzed using a general multivariate statistical algorithm. MATERIALS AND METHODS: The primary steps of the algorithm are to: (1) preprocess data to reduce interpatient and intrapatient variation of tissue spectra from the same diagnostic category, without a priori information, (2) dimensionally reduce the pre-processed spectral data using Principal Component Analysis, and (3) develop a probability based classification scheme based on logistic discrimination using the diagnostically useful principal components. The algorithm was tested on cervical tissue spectra acquired from 165 sites at 380 nm excitation and from 147 sites at 460 nm excitation. A retrospective and prospective estimate of the algorithm's performance was determined. RESULTS: At 460 nm excitation, (1) SILs can be differentiated from normal squamous tissues with an average sensitivity and specificity of 91% +/- 1.3 and 75.5% +/- 1, respectively; furthermore, (2) high grade SILs can be differentiated from low grade SILs with an average sensitivity and specificity of 80% +/- 4 and 76% +/- 5, respectively. In addition, using tissue spectra at 380 nm excitation, SILs can be differentiated from normal columnar epithelia and inflammation with an average sensitivity and specificity of 77% +/- 1 and 72% +/- 9, respectively. CONCLUSIONS: Fluorescence spectra at multiple excitation wavelengths are essential for the detection and differential diagnosis of SILs at colposcopy.

Algorithms↗

PubMed1996

Growth inhibition of human cervical cancer cells with the recombinant adenovirus p53 in vitro.

Human papillomavirus (HPV) has been identified in the majority of invasive cancers of the uterine cervix sampled and has been found to contribute in a significant way to the genesis of human cervical cancer. HPV has two transforming genes that encode the oncoproteins E6 and E7. E6 can form complexes with p53 and promote p53 degradation. We introduced wild-type p53 into a cervical cancer cell line via a recombinant adenoviral vector, Ad5CMV-p53. Human cervical cancer cell line HeLa, which has HPV type 18 and wild-type p53, was used in this study. Cells were grown in RPMI medium supplemented with 10% heat-inactivated fetal bovine serum. Ad5CMV-p53 was created by inserting the cytomegalovirus promoter, wild-type p53 cDNA, and SV40 polyadenylation signal in a minigene cassette into the E1-deleted region of the modified Ad5 adenovirus. The transduction efficiency was 100% when a dose ensuring a multiplicity of infection of 100 or greater was used. The p53 protein was detected in Ad5CMV-p53-infected cells by immunohistochemical and Western blot analyses. The growth of the Ad5CMV-p53-infected cells was greatly suppressed as detected by both cell count and [3H]thymidine incorporation assay. These data suggest that transfection of HPV-positive cervical cancer cells with a wild-type p53 gene in a form such as Ad5CMV-p53 is a potential novel therapy for cervical cancer.

Adenoviridae↗

PubMed1996

Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA to human cervical cancer cells.

To explore the potential of an adenoviral antisense RNA transcript for gene therapy of cervical cancer, we introduced the antisense RNA transcript of E6 and E7 genes of human papillomavirus (HPV) 16 into cervical cancer cells harboring HPV 16 via a recombinant adenoviral vector, Ad5CMV-HPV 16 AS and analyzed the effects of expression of these genes on cell growth and tumor growth. Ad5CMV-HPV 16 AS contains the cytomegalovirus-promoter, E6 and E7 genes of HPV 16 in antisense orientation, and the SV40 polyadenylation signal in a mini-gene cassette, which is inserted into the E1-deleted region of modified adenovirus 5. The entire E6/E7 region of HPV 16 was amplified by polymerase chain reaction (PCR) before cloning into the mini-gene cassette. By reverse transcriptase-PCR, HPV 16 E6/E7 antisense RNA was detected in SiHa cells infected with Ad5CMV-HPV 16 AS. The growth of the Ad5CMV-HPV 16 AS-infected cells was greatly suppressed, as evidenced by a decrease in cell count. The growth inhibitory effect of Ad5CMV-HPV 16 AS was significantly enhanced by an adenoviral p53 construct, Ad5CMV-p53. In an ex vivo study in nude mice, tumorigenicity was completely inhibited in mice injected with Ad5CMV-HPV 16 AS-infected SiHa cells. These data suggest that transfection of cervical cancer cells with HPV 16 E6/E7 antisense RNA in a form such as Ad5CMV-HPV 16 AS is a potential novel approach to the therapy of HPV 16-positive cervical cancer.

Adenoviridae↗

PubMed1996

Adenocarcinoma in situ of the cervix: significance of cone biopsy margins.

OBJECTIVE: To evaluate the treatment and outcome of patients with adenocarcinoma in situ of the cervix, with special emphasis on cone biopsy margins. METHODS: Sixty-one women with adenocarcinoma in situ of the cervix treated between April 1984 and December 1993 were identified. Medical records and histologic material were reviewed. Mixed lesions with both adenocarcinoma in situ and squamous cervical intraepithelial neoplasia (CIN) were included. RESULTS: The mean age of the patients was 35.9 years. Fifty-five of the 61 (90%) patients had cone biopsies, and 44 of these 55 (80%) subsequently had hysterectomies. Eight women (13%) had associated invasive cancer. Among 50 patients in whom the status of the margins was confirmed, 23 (46%) had positive margins and 27 (54%) had negative margins. Of 23 women with positive margins, 19 had hysterectomies and ten of the 19 (53%) had residual disease in the uterus. Of 27 patients with negative cone margins, 21 had hysterectomies, and seven of the 21 (33%) had residual disease in the uterus. Two women with negative margins who did not have hysterectomies developed recurrent disease. Fifty-five of the total series of 61 patients followed-up for a median of 57 months (range 17-132) had no evidence of disease at last follow-up. CONCLUSION: Women with adenocarcinoma in situ of the cervix often have residual disease in the uterus, regardless of whether the margins on cone biopsy are positive or negative.

Adenocarcinoma↗

PubMed1996

Transgene expression in the rhesus cervix mediated by an adenovirus expressing beta-galactosidase.

OBJECTIVES: More than 90% of cervical cancers are positive for human papillomavirus, which functionally represses p53 and pRb. The remainder have been found to contain p53 mutations. Gene therapy involves insertion of a functioning gene into a patient to correct a genetic abnormality. STUDY DESIGN: The ability of a beta-galactosidase adenovirus to mediate transgene expression in the rhesus cervix was evaluated. Three different doses and two different entry techniques of virus were investigated. RESULTS: The ideal dose determined by X-galactosidase staining was 2 x 10(10) plaque-forming units, and the injection method yielded better staining than did abrasion with topical application. Increased adenoviral-specific immunoglobulin G antibody response in the injected monkeys confirmed the results. CONCLUSION: High transduction efficiency by use of adenoviral vectors can be achieved in the cervix. Reversing the effects of human papillomavirus and p53 mutations with gene therapy may become a novel therapy for invasive and preinvasive cervical cancer.

Adenoviridae↗

PubMed1996

Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths.

A portable fluorimeter was developed and utilized to acquire fluorescence spectra from 381 cervical sites in 95 patients at 337, 380 and 460 nm excitation immediately prior to colposcopy. A multivariate statistical algorithm was used to extract clinically useful information from tissue spectra acquired in vivo. Two full-parameter algorithms were developed using tissue fluorescence emission spectra at all three excitation wavelengths (161 excitation-emission wavelength pairs) for cervical precancer (squamous intraepithelial lesion [SIL]) detection: a screening algorithm that discriminates between SIL and non-SIL with a sensitivity of 82 +/- 1.4% and specificity of 68 +/- 0.0%, and a diagnostic algorithm that differentiates high-grade SIL from non-high-grade SIL with a sensitivity and specificity of 79 +/- 2% and 78 +/- 6%, respectively. Multivariate statistical analysis was also employed to reduce the number of fluorescence excitation-emission wavelength pairs needed to redevelop algorithms that demonstrate a minimum decrease in classification accuracy. Two reduced-parameter algorithms that employ fluorescence intensities at only 15 excitation-emission wavelength pairs were developed: the screening algorithm differentiates SIL from non-SIL with a sensitivity of 84 +/- 1.5% and specificity of 65 +/- 2% and the diagnostic algorithm discriminates high-grade SIL from non-high-grade SIL with a sensitivity and specificity of 78 +/- 0.7% and 74 +/- 2%, respectively. Both the full-parameter and reduced-parameter screening algorithms discriminate between SIL and non-SIL with a similar specificity (+/-5%) and a substantially improved sensitivity relative to Pap smear screening. A comparison of the full-parameter and reduced-parameter diagnostic algorithms to colposcopy in expert hands indicates that all three have a very similar sensitivity and specificity for differentiating high-grade SIL from non-high-grade SIL.

Algorithms↗

PubMed1996

Cervical human papillomavirus infection and intraepithelial neoplasia: a review.

Cervical human papillomavirus (HPV) infections and intraepithelial neoplasias are precursors to cervical cancer, the second most common cancer in women worldwide. HPV satisfies the epidemiologic criteria for causality; the role of other cofactors is under study. Natural history studies show that most low-grade lesions (productive HPV infections) regress or persist, whereas high-grade lesions (those with integrated HPV DNA) progress. Immunobiologic studies demonstrate that infection peaks in the early 20s, leading to a 10- to 20-year period of persistent infection, before finally progressing to a preinvasive or invasive lesion. Papanicolaou (Pap) screening has lowered the morbidity and mortality from cervical cancer in every country in which screening programs have been introduced. The diagnostic strategy for an abnormal Pap smear includes colposcopy; the role of HPV DNA testing in screening or diagnosis remains unclear. Patients are treated with cervical ablation, cone biopsy, or chemopreventive agents. Efforts to strengthen screening and prevention, as well as new directions for research, are needed.

Female↗

PubMed1996

Detection of genomic alterations in human cervical cancer by two-dimensional gel electrophoresis.

Two-dimensional gel electrophoresis was used to comprehensively scan the whole genome of 6 cervical intraepithelial neoplasia (CIN) lesions, 7 cervical squamous cell carcinomas, 1 cervical adenosquamous cell carcinoma, and 2 cervical adenocarcinomas for multiple genetic alterations, such as DNA amplification, chromosome deletion, loss of heterozygosity, and chromosome translocation, as compared with the paired normal tissues. DNA spot analysis of the genomic 2-dimensional gels was performed by a computer color overlay system and by spot recognition software allowing for objective spot comparison and quantitation. Nine spots were found to be amplified in the cervical carcinomas while two amplified spots were detected in the CIN III lesions. Fourteen DNA spots were either reduced in their intensity or absent in cervical carcinomas as compared to their normal paired tissues. Reduction of intensity in 6 spots was observed in the 5 CIN III lesions. These genetic alterations may represent changes in cancer genes that are associated with human cervical carcinogenesis. Further characterization of these alterations may be significant to the understanding of cervical tumorigenesis and to the development of biomarkers for clinical trials in cancer chemoprevention.

Adenocarcinoma↗