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Outcome of cold coagulation for the treatment of cervical intraepithelial neoplasia in a department of genitourinary medicine.

OBJECTIVE: To evaluate the outcome of "cold coagulation" as a treatment modality for major grade cervical pathology, cervical intraepithelial neoplasia (CIN 2 and 3) in a department of genitourinary medicine. DESIGN: Prospective programme trial with 18 month follow-up of patients undergoing "cold coagulation" of the cervical transformation zone following colposcopic assessment and biopsy. SETTING: A genitourinary medicine colposcopy clinic. PATIENTS: 125 female patients with histologically proven major cervical pathology (CIN 2 and 3). The mean age of the patients was 24.5 years; 73% were unmarried, 43% currently smoked and 62% had a history of exposure to the human papilloma virus. MAIN OUTCOME MEASURES: Eradication of cervical abnormality with cytological findings at 4, 8 and 12 months and colposcopy at 18 months, with intervention colposcopic assessment if follow-up cytology was abnormal. RESULTS: Eradication of CIN was achieved in 96.5% of patients, the majority of treatment failures being detected at first cytology. Attendance for follow-up was good, with only a 16% default rate. Final colposcopy yielded five treatment failures. No major complications were noted. CONCLUSION: These results confirm that "cold coagulation" provides an acceptable, efficient and effective, low cost consumer friendly treatment for CIN 2 and CIN 3 in an out-patient genitourinary medicine colposcopy clinic.

Adolescent↗

Long-term administration of intravaginal dehydroepiandrosterone on regression of low-grade cervical dysplasia--a pilot study.

Although many dysplastic cervical lesions regress spontaneously, treatment is common due to concern for progression. Lesions persist or progress in women whose immune systems are unable to clear infection by human papillomavirus (HPV). Dehydroepiandrosterone (DHEA) is an adrenal steroid that has both immune modulatory and tumor inhibitory activity. A pilot study was conducted to examine the feasibility, safety and potential efficacy of intravaginal DHEA in women with low-grade cervical dysplasia. Twelve women with low-grade dysplasia, confirmed by colposcopic exam, were given 150 mg of intravaginal micronized DHEA daily for up to 6 months. Follow-up evaluations of the cervix were done at 3 and 6 months of use. DHEA, DHEA-S, androstenedione and testosterone levels were also measured. By the end of the study period, 10 of the 12 women (83%) had no evidence of dysplasia; the remaining 2 had normal colposcopic exams but cytology showing atypical cells of undetermined significance. There were no serious side effects. Androstenedione levels were elevated at 3 months, whereas testosterone levels were unchanged over the course of treatment. The results suggest that intravaginal DHEA is safe and well tolerated and may promote regression of low-grade cervical lesions. Further study is needed to establish efficacy.

Administration, Intravaginal↗

Measurements of ascorbic acid and glutathione in exfoliated cervicovaginal epithelial cells of smokers and women with cervical dysplasias.

This report emphasizes the ability to quantify ascorbic acid (AA) and reduced glutathione (GSH) levels in exfoliated cervicovaginal epithelial cells obtained by a lavage technique. Sixty-two women with abnormal Papanicolaou smears underwent colposcopic examinations. Colposcopic lesions were biopsied and histopathologically graded. Marked variations in the number of cells and in the levels of AA and GSH were observed. In cigarette smokers, the number of exfoliated cells retrieved was significantly higher (p less than 0.05, by Student's t test). The simultaneous investigation of biochemical and virologic parameters in exfoliated cervicovaginal epithelial cells, in conjunction with the known cytopathologic and epidemiologic risk variables, provides a novel approach to elucidate factor(s) that may inhibit or promote cervical carcinogenesis in designed prospective studies.

Adult↗

Acantholytic cells exfoliated from pemphigus vulgaris of the uterine cervix. A case report.

BACKGROUND: Pemphigus vulgaris of the uterine cervix is rare and almost always associated with cutaneous or mucosal lesions elsewhere on the body. Without a history of pemphigus, acantholytic cells in cervical smears may be misdiagnosed as malignant ones. CASE: A 52-year-old female presented with a vaginal discharge, and a routine cervical smear was collected for cytology. The smear displayed atypical cells lying singly and in loose clusters, having vesicular nuclei, a thin nuclear membrane, prominent nucleoli and well-defined cytoplasmic margins. These were labeled atypical glandular cells of undetermined significance, and colposcopic examination and biopsy were advised. On colposcopy vesicular lesions and erosions were noticed on the cervix. The biopsy revealed typical intact as well as denuded suprabasal bullae of pemphigus vulgaris. On reevaluation of the cytologic smear, the cytomorphologic features correlated well with the acantholytic cells of pemphigus. Thorough reexamination of the patient revealed 2 tiny vesicles on the oral mucosa that, on biopsy, confirmed the diagnosis of pemphigus vulgaris. CONCLUSION: Cytopathologists should be aware of the typical cytomorphologic features of pemphigus vulgaris and, in an appropriate clinical setting, should be able to diagnose or at least suspect this entity in even rare sites like the cervix. A false positive diagnosis of malignancy can be avoided if the cytologic findings are judiciously correlated with the history and with clinical and colposcopic examinations.

Acantholysis↗

Comparing the accuracy of ThinPrep Pap tests and conventional Papanicolaou smears on the basis of the histologic diagnosis: a clinical study of women with cervical abnormalities.

OBJECTIVE: To confirm that the ThinPrep Pap test (TP) is as effective as or more effective than the conventional Papanicolaou smear (CS) in detecting epithelial cell abnormalities in a population with cervical abnormalities. STUDY DESIGN: In a blinded, split-sample, matched-pair study, a CS was prepared using a cytobrush, and then TP slides were prepared from the remainder of the sample. All slides were evaluated as defined and classified by the Bethesda System. The results of the two cytologic tests were compared in 483 women relative to the histologic diagnoses of subsequent colposcopically directed cervical biopsies in 158 cases. RESULTS: The cytologic diagnoses from the two methods agreed exactly in 91.4% of cases. The comparison between the two cytologic diagnoses with reference to the histologic diagnosis of subsequent colposcopically directed cervical biopsies showed that TP was significantly more specific for diagnosing lesions than was CS. The sensitivity of the two methods was equivalent. CONCLUSION: In a population with cervical abnormalities, TP is more specific than and as effective as CS in detecting cervical epithelial cell abnormalities. TP improved the specificity of disease detection by reducing the atypical squamous cells of undetermined significance category and/or false positive cases.

Biopsy↗

High-grade cervical squamous intraepithelial lesion during pregnancy.

AIMS AND BACKGROUND: An increasing incidence of high-grade squamous intraepithelial lesion (HSIL) has been observed among young women. Consequently, an increased number of cases are being discovered during pregnancy. We analyzed the clinical and therapeutic management of HSIL during pregnancy. METHODS: A retrospective study was conducted from 1979 to 1998, and 58 registries of women with a cytological or histological diagnosis of HSIL during the pregnant-puerperal period were reviewed. Information obtained from medical records included age, gestational age at diagnosis, parity, age of first intercourse, number of sexual partners before pregnancy, tobacco use, cytologic and colposcopic findings, route of delivery, postpartum follow-up, and treatment. This information was compared with a non-pregnant control group with HSIL. RESULTS: The average age of pregnant women with HSIL was 27.9 +/- 5.2 years. The cytologic or histologic diagnosis of HSIL was made in the first trimester in 12 (20.7%) women and in the second trimester in 30 (51.7%) women. Average parity was 2.8 +/- 2 deliveries. Age of first intercourse ranged from 13 to 29 years (16.1 +/- 3.3). Thirty-two women (55.1%) had more than one sexual partner before pregnancy. Thirty-seven (63.8%) refereed tobacco use. According to the aforementioned aspects, no statistical difference was found in relation to control, except to cervical ectopia, which was more frequent in pregnant women (56.9% versus 42.6%). From the total of 58 pregnant women with cytologic or biopsy HSIL diagnosis, 53 had HSIL diagnosis made on cervical biopsy directed by colposcopy performed during the pregnancy; 44 (83%) of them were submitted to conservative management. HSIL was diagnosed by cervical biopsy in postpartum evaluation in 76% pregnant women with vaginal delivery and 78.6% women who underwent cesarean section. CONCLUSIONS: A conservative management of HSIL in pregnancy is proposed, with colposcopic evaluation during gestation and postpartum, regardless of route of delivery.

Adolescent↗

Contribution of cytology, colposcopy, target biopsy and conization to the early diagnosis of precancerous and cancerous lesions of the cervix uteri.

The study is based on 334 cytologic suspect or positive women observed in the area of Florence. Cytologic diagnoses of dysplasia, carcinoma in situ (CIS), and invasive carcinoma are related to the histologic reports. To the same histologic reports are related the colposcopic aspects. Lastly, diagnoses made by target biopsy are compared with the final diagnoses made by cone biopsy. The 3 diagnostic methods and their diagnostic accuracy are then compared. As regards dysplasia, the diagnostic precision of cytology is 40.2% and for target biopsy in 76.9%. In the diagnosis of CIS, cytology shows a diagnostic accuracy (77.7%) that is a little lower than that of target biopsy (81.7%). In invasive carcinoma, cytology has a good diagnostic precision (88.2%), which becomes 100% if the diagnosis is made by target biopsy. The correlation between colposcopic aspects and histologic reports is not very reliable. We conclude that cytology is a valid test in an extensive mass screening, that colposcopy is essential to execute target biopsy, and that the latter is useful in defining dysplasia and invasive carcinoma diagnoses. On the contrary, in the case of CIS, target biopsy does not greatly increase cytology diagnostic precision.

Biopsy↗

Quality control for colposcopy in the Florence screening program for cervical cancer.

The authors report on the quality control for colposcopy adopted in the Florence District screening program. The sensitivity of colposcopy was determined on all cases of CIN III recorded in the local cancer registry in a four-year period. However although this showed that a centralized colposcopic clinic employing a limited number of expert operators is superior to the performance of colposcopy in private practice, such a parameter was impractical for further routine quality control since differences among operators were too small and statistically insignificant. Other parameters for quality control were chosen, namely a) the rate of colposcopically directed biopsies performed, b) the detection rate of CIN II or more severe lesions, and c) the positive predictive value of a directed biopsy for CIN II or more severe lesions. Analysis of these indicators after stratification by cytologic report allows the identification of those operators who need additional training and provides useful information for colposcopists to optimize their diagnostic and operative criteria.

Adult↗

Training in colposcopy: experience with a videocolposcopy test.

The authors evaluate the results of a videocolposcopy test (330 total cases, 12 cases of histologically confirmed CIN2 or more severe lesions) taken by 9 accredited and 17 unaccredited colposcopists during 1995. Seven of 9 accredited and 4 of 13 unaccredited colposcopists reached the requested standard (sensitivity > 90%, biopsy rate < 60%). Performance was definitely better when the test was not blind to the cytologic report (4 of 13 reached the requested standard) with respect to blind reading (none of 17). The study confirmed that colposcopy at unaccredited practices is poorly accurate. Colposcopic assessment of patients with abnormal smears should be centralized in accredited practices, which should undergo periodic quality control to guarantee screening efficacy. Tape-recorded videocolposcopy tests are a good, simple, practical and inexpensive method for interobserver quality control of colposcopic performance.

Clinical Competence↗

Subclinical human papillomavirus infection of the male lower genital tract: colposcopy, histology and DNA analysis.

In 25 partners of women with genital human papillomavirus (HPV) infection or cervical intraepithelial neoplasia, colposcopic examination revealed the existence of subclinical HPV infection of the male lower genital tract in 22 cases. It manifested either as short papillae tipped with acetowhite changes, or flat acetowhite lesions on the foreskin, glans, periurethral region, scrotum, perineum and/or perianal region. Multiple lesions involving several anogenital areas were common. Some of these abnormalities were small and inconspicuous. Of these 22 cases, 17 had histological evidence of HPV infection. Although Southern blot hybridization detected HPV DNA in only one case, polymerase chain reaction (PCR) analysis revealed HPV DNA in 20 cases. There were 10 cases of HPV 16. Subclinical HPV disease is best identified by colposcopy and confirmed by PCR. In treating HPV disease, colposcopic recognition of subclinical HPV disease forms an essential part of the management plan.

Biopsy↗

Ten year follow-up study of women presenting to a genitourinary medicine clinic with anogenital warts.

One hundred heterosexual women presenting at our clinic in 1979 with anogenital warts, were reviewed 10 years later. Median duration of warts following initial clinic attendance was 2 months (range 0-120 months). In 1979 cervical PAP smear results were available for 76 patients; cervical intraepithelial neoplasia (CIN) was seen in 15/76 (19.7%) women; 3 (4%) women had low grade CIN, 12 (15.7%) women had high grade CIN. Nineteen women had had treatment for CIN between 1979 and 1989, 7 laser ablation, 9 cone biopsy, 2 laser ablation and cone biopsy, and one woman laser ablation, cauterization and cone biopsy. At 10-year follow-up in 1989 4/100 women had anogenital warts, 12/100 women had cytological evidence of CIN (7 low grade, 5 high grade), and 37/100 women had CIN detected on colposcopic biopsy (31 low grade, 6 high grade). No women developed invasive cervical carcinoma during the study period. CIN lesions, detected in 1979, regressed without any treatment in 2 women. Colposcopic biopsy was 3.1 times more sensitive than single cervical PAP smear at detecting CIN (4.4 times as sensitive in detecting low grade CIN; 1.2 times as sensitive in detecting high grade CIN). In 1989 CIN was detected in 7/19 (36.8%) of women who had undergone cervical treatment between 1979 and 1989, and in 35/81 (43.2%) of women having no cervical treatment within this period (chi squared P greater than 0.5). These findings suggest that cervical laser ablative therapy and cone biopsy do not in the long term influence the natural history of cervical human papilloma virus-associated disease (CIN) in women with anogenital warts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Telecolposcopy - a feasibility study in primary care.

Organized cervical screening has reduced the incidence of invasive cervical cancer, but this has resulted in large numbers of women requiring investigation. We have investigated the negative predictive value of colposcopy and used telemedicine to develop a secondary screening technique for use in primary care. A video-colposcope was used to record video-clips, which were subsequently transmitted to a specialist for interpretation. The gold standard for the comparison was the opinion of the colposcopist who examined the women in the hospital colposcopy clinic. Eighty-one out of 97 women were studied by both techniques. Using a diagnosis of normal or abnormal, telecolposcopy had a sensitivity of 88.9% and a specificity of 93.3%. There was very good agreement between the telecolposcopy screener and the colposcopist (Cohen s kappa statistic = 0.70). Furthermore, telecolposcopy screening did not grade any cases of colposcopic high-grade cervical intraepithelial neoplasia as normal. The pilot study has established the validity of diagnosing from transmitted computerized video-clips.

Colposcopy↗

Changes in lipid peroxidation and antioxidant trace elements in serum of women with cervical intraepithelial neoplasia and invasive cancer.

This study investigated serum lipid peroxidation, antioxidant capacity, and trace element levels in Korean women as related to uterine cervical neoplasia. Twenty-eight subjects had cervical intraepithelial neoplasia (CIN), 36 had invasive cervical cancer, as determined by a colposcopically directed biopsy, and controls included 44 subjects with normal colposcopic findings. Significantly lower selenium (Se) and zinc (Zn) levels and higher copper/Zn ratios were found in both CIN and cancer patients compared with the controls. Serum malondialdehyde levels decreased significantly in the order CIN>cancer>control, implying the involvement of reactive oxygen species at the precancerous stage, that is, prior to progression into invasive cervical cancer. Serum glutathione peroxidase activity was significantly lower in patients with CIN or cancer than controls, and total antioxidant ability decreased from controls to CIN to cancer (P < 0.0001). This study demonstrated the involvement of lipid peroxidation, decreased Se and Zn levels, and an impaired serum antioxidant system in the pathogenesis of cervical dysplasia. Further research is needed to examine the possibility of an effective chemopreventive treatment in cervical cancer based on enhancing the endogenous antioxidant system.

Adult↗

Characteristics of apparently false-negative digene hybrid capture 2 high-risk HPV DNA testing.

This study characterized cases with a negative high-risk Hybrid Capture 2 (HRHC2; Digene, Gaithersburg, MD) test result with concurrent or follow-up biopsy-confirmed high-grade cervical intraepithelial neoplasia (CIN 2/3). From 2,306 HRHC2 tests, 10 negative results were identified with CIN 2/3 (false-negative rate, 4.5%). The majority of the patients had abnormal colposcopic findings and high-grade squamous intraepithelial lesion (HSIL) shown by concurrent cytologic examination, although with few abnormal cells. No trend was evident in the location of the dysplastic epithelium or overall lesion size. In 4 tests, the relative light units over cutoff was more than 0.4 but less than 1.0, suggesting that low quantities of human papillomavirus (HPV) DNA were present in the sample. The negative predictive value for HRHC2 testing may be compromised when the copy number of the HPV DNA is low, and a negative HRHC2 test result may be falsely negative in patients with abnormal colposcopic findings or concurrent cytologic findings showing HSIL.

Adult↗

Human papillomavirus screening in pediatric victims of sexual abuse.

OBJECTIVE: To evaluate for the presence of subclinical human papillomavirus (HPV) in cases of suspected sexual abuse in children. DESIGN: Prospective data collection via interviews, physical examination, colposcopic examination, and tissue sampling by a surface swab technique. SETTING: A total of 40 pediatric patients ranging in age from 1 to 16 years who were referred to the Special Assessment and Management Clinic at Cardinal Glennon Children's Hospital, St Louis, MO, for probable or confirmed sexual abuse. INTERVENTIONS: In addition to colposcopic examination for physical signs of abuse, the patients were screened for evidence of sexually transmitted diseases, including syphilis, gonorrhea, and Chlamydia. At that time, surveillance sampling of the throat, vaginal introitus, and/or rectum by a simple, rapid surface swab technique was performed to detect the presence of HPV. MEASUREMENTS: Template DNA was extracted from cotton swabs and analyzed using polymerase chain reaction analysis. RESULTS: Human beta-globin sequences were detected in 58 (83%) of 70 specimens obtained from 40 patients, indicating successful processing had occurred. Using a consensus L1 primer-probe set capable of detecting multiple HPV genotypes, 2 (3%) of 58 samples from 2 (5%) of 40 patients were positive for HPV 16. None of the other 56 specimens yielded evidence of HPV. Appropriate positive and negative controls were included in each assay. CONCLUSIONS: Our results suggest that subclinical HPV infection is possible, but not commonly associated with sexual abuse in children from St Louis, MO. In this group of children without condyloma, HPV 16 was the only type identified.

Adolescent↗

The prevalence of genital human papillomavirus infections in abused and nonabused preadolescent girls.

OBJECTIVE: To compare the prevalence of genital human papillomavirus (HPV) infections in sexually abused and nonabused preadolescent girls and assess the feasibility of conducting a longitudinal study of the natural history of HPV infection in this population. METHOD: Consecutively referred, 5- to 12-year-old girls who were evaluated for sexual abuse by a Child Advocacy and Protection Team were invited to participate in the study. During a standard forensic medical examination, 2 specimens for HPV testing were obtained (one by rubbing a Dacron swab over the perineum and the other by lavaging the vagina with phosphate-buffered saline). The specimens were evaluated for HPV DNA by polymerase chain reaction using MY09/11 consensus primers and high-risk (16,18,31,33,35,39,45,51,52, 56,58) and low-risk (6,11,42,43,44) types were detected with a solution hybridization assay, the SHARP Signal System (Digene Diagnostics). The genital area was examined for warts and subclinical, colposcopic evidence of HPV. Participants were invited to return for longitudinal evaluation at 4-month intervals for 2 years. RESULTS: Sexual abuse was confirmed in 29 (72.5%) of the 40 study participants, suspected in 2 (5%), and ruled out in 9 (22.5%). None of the girls had genital warts or abnormal colposcopic findings. HPV DNA was detected in 5 (16%) of the 31 girls with confirmed or suspected sexual abuse (1 with high-risk and 4 with low-risk types) and none of the nonabused girls (Fisher's exact test). Girls who tested positive and negative for HPV did not differ significantly in age or type of abuse. Despite close telephone follow-up and numerous attempts to schedule appointments, none of the participants returned for follow-up. CONCLUSIONS: Genital HPV infection is more common among sexually abused than nonsexually abused girls, with the majority of infections not clinically apparent. Because it is so difficult to study the natural history of these infections in abused children, it may be necessary to draw inferences about the long-term sequelae of pediatric HPV infections from longitudinal studies of girls who voluntarily initiate sexual activity soon after menarche.

Child↗

High prevalence of cervical dysplasia in STD clinic patients warrants routine cytologic screening.

The results of routine cervical cytology screening at a Planned Parenthood Center (PPC) clinic were compared to those at a nearby sexually transmitted diseases (STD) clinic in Seattle. Cervical cytologic findings were consistent with cervical intraepithelial neoplasia (CIN), grades 1 (mild dysplasia), 2 (moderate dysplasia), or 3 (severe dysplasia to carcinoma in situ) in 502 (5.9 per cent) of 8,504 PPC patients and 87 (11.4 per cent) of 764 STD patients (p = .001). This rate for STD patients is five times that reported for the general population. Sixty-three PPC patients and 31 STD patients with screening smears consistent with CIN 1 or 2 underwent further prospective study by us, including repeated cytologic and colposcopic examinations. Thirty-seven (59 per cent) of 63 PPC patients and 26 (84 per cent) of 31 STD patients (p = .02) had at least on additional smear or colposcopy consistent with CIN and were advised to undergo cervical biopsy. Among those who underwent recommended biopsy, CIN was confirmed histologically in 15 (50 per cent) of 30 PPC patients and 11 (61 per cent) of 18 STD patients. Thus, the proportion of patients who had screening cytologic findings consistent with CIN, the proportion with persistent cytologic or colposcopic findings consistent with CIN on retesting, and the proportion of those biopsied who had histologically confirmed CIN, all were higher for STD than for PPC patients. There is a serious need for cytologic screening in STD clinics throughout the nation.

Adolescent↗

Cryosurgery for dysplasia of the uterine ectocervix. A randomized study of the efficacy of the single- and double-freeze techniques.

This prospective, randomized study of 142 women with mild or moderate dysplasia of the uterine ectocervix shows that the double-freeze technique is significantly more effective than the single-freeze technique, the recurrence rates being, respectively, 6.2% and 16.3%. The highest recurrence rate was found in the group treated with a single freeze and having the most extensive portio involvement. All patients were examined colposcopically before cryosurgery in order to exclude patients with lesions extending into the cervical canal and in order to evaluate the size of the lesion. Recurrent lesions were usually diagnosed within the first year (75%) and in only one patient more than 2 years after treatment. None of the patients developed invasive cancer. The mean follow-up period was 27 months (24-42 months). We consider cryosurgery to be an acceptable treatment for selected patients. Our criteria for entry were mild or moderate dysplasia of the uterine ectocervix, and colposcopic visualization of the entire transformation zone to ensure that the lesion does not extend into the cervical canal. Our experience from the present study is that the following criteria should be added: the portio involvement must not be too extensive and the patient must agree to follow-up examination. When these conditions are fulfilled, future treatment in our department will consist of a double freeze extending 3 mm beyond the lesion, with a thaw interval of 4 min.

Adolescent↗