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A Ferenczy

Publications and source records attributed to A Ferenczy.

At least 37 records · Page 2Linked to original sources

Low false-negative rate of PCR analysis for detecting human papillomavirus-related cervical lesions.

Although PCR analysis is a sensitive test for detection of human papillomavirus (HPV) in the cervix, the proportion of cases of cervical dysplasia missed, or the false-negative rate, has been unknown. We determined the accuracy of PCR analysis for HPV DNA as a predictor of HPV-related cervical lesions in a cross-sectional study of sexually active women, aged 18 to 50 years, from the University of Michigan Family Medicine HPV study. Of 133 eligible participants, 41 underwent colposcopy because of a positive result for HPV of the cervix by the PCR method and 92 underwent screening colposcopy with biopsy prior to knowing the HPV PCR results. Twenty-four of those screened were subsequently found to also be HPV DNA positive. In those found to be HPV positive, histological studies revealed the presence of condyloma or cervical intraepithelial neoplasia in 16 women (24.6%) and changes suggestive of condyloma in 5 (7.6%). No HPV-negative woman had an abnormal biopsy or cytology report (P = 0. 000001). The false-negative rate (1 - sensitivity) for HPV PCR analysis for detection of the presence of a cervical HPV-related lesion was 0% (95% confidence interval, 0 to 0.047), and the specificity was 60.7%. In summary, PCR analysis for HPV DNA had a very low false-negative rate for predicting HPV-related lesions of the cervix in a community-based population. This supports the validity of using the absence of HPV at the cervix, as determined by PCR testing, as an inclusion criterion for patients in control groups in studies dealing with low-grade cervical lesions.

Adolescent↗

Therapeutic approaches to genital warts.

Although many treatments are available for genital warts caused by human papillomavirus (HPV), none are uniformly successful in the treatment of this disease. Most current treatment options work by destroying affected tissue, either by a cytotoxic or a physically ablative mode of action. Interferons have antiviral, antiproliferative, and immunomodulatory activities, but these have not translated into a high level of cure rates against warts. With all current treatments, recurrent warts are common. Therapies currently being investigated include a 5-fluorouracil/epinephrine collagen gel that achieves high concentrations of 5-fluorouracil at the site of injection. Other new treatment modalities focus on activating the host's immune system or improving the delivery of therapeutic compounds to the affected site. Imiquimod, a novel immune-response modifier, induces interferon and a number of other endogenous cytokines. A cream formulation containing 5% imiquimod resulted in good total clearance rates and generally tolerable side effects in controlled clinical trials of patients with external genital warts. Perhaps the most effective means for managing HPV disease would be a vaccine that prevents the occurrence of genital warts. Although it is unlikely that such a vaccine will be introduced in the near future, preliminary studies indicate that it may be possible to develop suitable prophylactic and therapeutic vaccines.

Adjuvants, Immunologic↗

Human papillomavirus infection in postmenopausal women with and without hormone therapy.

OBJECTIVE: To determine whether postmenopausal hormone therapy is associated with high-risk human papillomavirus (HPV) infection. METHODS: The detection rate of HPV DNA was studied in cellular residue from liquid-based collection tubes taken from 180 postmenopausal hormone users attending a menopausal clinic and 126 postmenopausal nonusers. The samples were analyzed with a hybrid capture technique using a mix of high- to intermediate-risk viral RNA probes. In all patients, information on potential confounding factors for HPV infection, including sociodemographic, reproductive, and gynecologic characteristics, was obtained. RESULTS: The prevalence of HPV DNA in this cohort of postmenopausal women was 1% (three of 306); only two of the 180 current users and one of the 124 nonusers tested positive. Only one of the three women with HPV-positive tests had lesional tissue (i.e., vulvar condylomata acuminata). The remaining two HPV-positive women had negative cytology, colposcopy, and biopsy. In all three cases, viral burden was low, about 10 pg per cellular sample. The very low HPV prevalence precluded the analysis of correlation with age, ethnicity, education, sexual history, smoking, history of abnormal Papanicolaou smear, therapy for HPV-related lesions, and contraceptive use. CONCLUSION: Identification of high-risk HPV types in post-menopausal women is rare, as detected by hybrid capture in cellular residue from the liquid-based cytology-collection system. Postmenopausal hormone therapy does not appear to promote viral replication or the risk of carrying high-risk HPV DNA or related lesional tissue in the lower genital tract.

Aged↗

Endometrial histology and bleeding patterns in post-menopausal women taking sequential, combined estradiol and dydrogesterone.

OBJECTIVES: To determine the endometrial response and bleeding patterns in post-menopausal women who were given a sequential hormone replacement regimen with estradiol 2 mg and dydrogesterone 10 mg. METHODS: One-hundred-and-eighty-eight (188) post-menopausal women with amenorrhea of 6 months or longer, with FSH/estradiol (E2) levels in the post-menopausal range and normal endometrium were entered in the study. All patients received a daily dose of 2 mg E2 during day 1-14 of each 28 day cycle and 2 mg E2 combined with 10 mg dydrogesterone during cycle day 15-28. The total duration of treatment was 12 months (13 cycles of 28 days). RESULTS: The rate of adequate progestational response (secretory or atrophic) in the 146 patients who remained in the study for at least 356 days with 90% study medication compliance and received an endometrial biopsy after 13 cycles of study medication was 97.2%. Three patients had proliferative endometrium and one simple hyperplasia. Cyclic bleedings in the 153 women who remained on study medication for at least 76 days occurred in over 85% of all cycles; the day of onset occurring regularly on day 13 or 14 of the combined period; the mean duration of bleeding per cycle was approximately 5 days with most patients having (very) slight bleeding. Sixty percent of patients had no intermittent bleedings over the whole 12-month study period. The average incidence of intermittent bleeding in the remaining patients was only 2.7 and generally of very slight quantities and of short duration. Per evaluable cycle the percentage of patients with an intermittent bleeding varies from 4.6 to 9.8%. Only two patients discontinued therapy because of bleeding problems. A clear decrease in the incidence of typical menopausal symptoms, i.e. hot flushes and night sweats was observed by the first visit after 6 weeks of treatment. CONCLUSIONS: The endometrial safety of 2 mg E2 sequentially combined with 10 mg dydrogesterone is very good as determined by the histologic response of the endometrium. The incidence of cyclic bleedings with this combination therapy is very high as is the regularity of day of onset and duration of bleeding. Blood loss during intermittent bleedings was mild and of short duration.

Climacteric↗

Induction of p16 during immortalization by HPV 16 and 18 and not during malignant transformation.

The p16 (MTS1) tumour-suppressor gene is a cyclin-dependent kinase (cdk) inhibitor that decelerates the cell cycle by inactivating the cdks that phosphorylate the retinoblastoma tumour-suppressor gene (Rb) protein (pRb). In cervical cancers, pRb is inactivated by the HPV E7 oncoprotein or by mutations. The hypothesis of earlier reports was that the disruption of the p16/cdk-cyclin/Rb cascade is essential for malignant cervical transformation/carcinogenesis. We previously established in vitro model systems of cervical cancer representing four steps of oncogenic progression initiated by the two most common oncogenic HPVs in ectocervical and endocervical epithelial cells. This report used these systems to investigate the role of p16 in cervical cancers. A dramatic enhancement of the p16 RNA level was observed after immortalization by HPV 16 or 18. Furthermore, the p16 protein was newly observed following immortalization. However, no further changes were found for RNA or protein levels after serum selection or malignant transformation. For three cervical carcinoma cell lines, similar high levels of p16 expression were seen. Point mutations or homozygous deletions of p16 were not observed in the in vitro systems or in clinical specimens. These results suggest that the inactivation of the p16/cdk-cyclin/Rb cascade does not occur during malignant transformation but occurs during the immortalization by HPV in HPV-harbouring premalignant lesions, the in situ equivalent of immortalized cells. Also suggested is that p16 has no role in the specific malignant transformation step from immortal premalignant lesions during the carcinogenesis of HPV-initiated cervical cancers.

Adenocarcinoma↗

Loop electrosurgical excision procedure for squamous intraepithelial lesions of the cervix: advantages and potential pitfalls.

OBJECTIVE: to evaluate the advantages and pitfalls of the loop electrosurgical excision procedure as applied to the diagnosis and treatment of cervical cancer precursors. METHODS: Loop electrosurgical excision procedure using local anesthesia and colposcopic guidance was performed in an outpatient clinical setting in 1189 consecutive patients referred for colposcopy for an abnormal Papanicolaou smear during a period of 4 years. RESULTS: Of the 1189 patients, 915 (77%) were managed in one sitting with the "see and treat" approach, and in 274 patients endocervical curettage and cervical biopsies preceded loop electrosurgical excision procedure. One hundred nineteen (10%) patients were lost to follow-up. Twenty-one patients had either adenocarcinoma in situ (15) or microinvasive squamous cell carcinoma (six) in the loop electrosurgical excision procedure specimen, whereas the electroexcised specimens contained no lesional tissue in 166 (14%) patients. Cure (ie, disease-free at 6 months or longer) was observed in 92% of the 883 evaluable patients after a single treatment and 95% after a repeat loop electrosurgical excision procedure. High-grade squamous intraepithelial lesion was successfully treated with loop electrosurgical excision procedure in 287 (93%) of 309 patients. Complications, mainly intra- and postoperative bleeding, occurred in 7% of the patients. In most loop electrosurgical excision procedure-negative cases, the referral cytologic diagnosis or colposcopy and/or history were false-positive on review, or the biopsies performed before loop electrosurgical excision procedure removed smaller areas of abnormal tissue. CONCLUSION: Loop electrosurgical excision procedure using the see and treat approach should be limited to cytologically and colposcopically unequivocal intraepithelial lesions, and depth of excision should be controlled by colposcopy using loop electrodes of appropriate size. In doubtful cases, particularly in the young patient, disease should be ascertained by expert histology and colposcopy before definite therapy. Loop electroexcision represents an attractive means of diagnosing and treating cervical cancer precursors.

Adenocarcinoma↗

Tissue effects and host response. The key to the rational triage of cervical neoplasia.

Genital HPV infections are associated with a spectrum of lesions ranging from benign condylomata to invasive cancer and its precursor lesions. The transformation zone of the cervix is the most frequent target of the high-risk HPV types. Depending on the nomenclature used, cancer precursors are subdivided on the basis of their morphologic presentation into dysplasias (mild, moderate, and severe); cervical intraepithelial neoplasias (CIN I, II, and III); or low-grade and high-grade squamous intraepithelial lesions (LGSILs and HGSILs). The HGSILs (i.e., moderate and severe dysplasias, CIN II and III lesions) are recognized universally as cancer precursors. The LGSILs (i.e., very mild dysplasia and mild dysplasias, condylomata and CIN I lesions), have shown that one of the most important denominators of their cancer potential is the presence of intermediate and particularly high-risk HPV types. HPV typing provides the most rational basis for selecting women with LGSILs to be colposcoped and treated or given follow-up treatment with Pap smears. Until the clinical significance of HPV typing is known, management decisions may be based on an individual's risk factors such as age, compliance, past history of abnormal Pap smears, sexual habits, and access to adequate cytologic diagnosis.

Colposcopy↗

Diagnostic performance of Hybrid Capture human papillomavirus deoxyribonucleic acid assay combined with liquid-based cytologic study.

OBJECTIVE: Our purpose was to determine the diagnostic performance of human papillomavirus deoxyribonucleic acid testing when performed on liquid-based (Thin-prep) cytologic samples. STUDY DESIGN: Thin-prep cytologic study, human papillomavirus deoxyribonucleic acid assay with probes for high oncogenic risk human papillomavirus types (16, 18, 31, 33, 35, 45, 51, 52, and 56), and cervical biopsies on women referred to colposcopy for an abnormal Papanicolaou smear were performed. RESULTS: Of the 364 patients, 186 (51.6%) had a low-grade squamous intraepithelial lesion or worse by histologic diagnosis. Human papillomavirus deoxyribonucleic acid quantitation was correlated with a histologic diagnosis of squamous intraepithelial lesion (p < 0.0001) and the morphologic severity (p < 0.01). The combination of Thin-prep cytologic study and human papillomavirus deoxyribonucleic acid testing correctly identified 87.7% of histologic low-grade lesions and 95.1% of the women with high grade lesions and invasive cancer (p < 0.01). CONCLUSIONS: A liquid-based cytologic system provides adequate material for concomitant human papillomavirus testing. Addition of human papillomavirus testing to Thin-prep cytologic study provides significant gains in diagnostic accuracy over either cytologic study or human papillomavirus deoxyribonucleic acid testing alone.

Adolescent↗

Management of patients with high grade squamous intraepithelial lesions.

BACKGROUND: The advent of modern electrosurgical equipment has allowed for outpatient excisional procedures rather than ablative therapy for patients with high grade squamous intraepithelial lesions (HGSILs). METHODS: The advantages and disadvantages of the commonly used ablative and excisional techniques for treatment of HGSILs were reviewed. RESULTS: Electrofulguration or cryotherapy for HGSILs smaller than 2.5 cm results in a 90% cure rate after a single treatment, but the cure rate drops to 50% for treatment of large HGSILs. Carbon dioxide laser therapy has resulted in high cure rates, but the necessary equipment is expensive. Excisional techniques for HGSILs of any size and distribution provide for a greater than 90% cure rate after a single session. Complication rates arising from use of excisional techniques vary from 5% to 20%, depending on the method used; ablative techniques have a uniformly low complication rate (2%). The risk of inadvertently treating underdiagnosed invasive cancer is reduced with excisional but not with ablative methods. Of the excisional methods used to treat HGSILs, the loop electrosurgical excision procedure (LEEP) appears to be the most cost-effective. CONCLUSIONS: The use of ablative techniques for small ectocervical HGSILs may be appropriate provided invasive cancer has been ruled out and the patient can be followed up long term. Loop electrosurgical excision procedure is the preferred excisional technique for lesions larger than 2.5 cm. The "see-and-treat" approach used with LEEP must be limited to only those lesions that are unequivocally verified by an expert in colposcopy and cytology. In questionable cases, the disease should be histologically ascertained by endocervical curettage and punch biopsies before therapy is undertaken.

Electrosurgery↗

Evaluation of the Hybrid Capture human papillomavirus deoxyribonucleic acid detection test.

OBJECTIVE: Our purpose was to evaluate the sensitivity and accuracy of a new, nonradioactive human papillomavirus deoxyribonucleic acid detection method. STUDY DESIGN: Cervical samples from 520 women were assayed for human papillomavirus deoxyribonucleic acid with both the Hybrid Capture test and polymerase chain reaction. RESULTS: Human papillomavirus deoxyribonucleic acid was detected with Hybrid Capture in 106 (42%) of 254 samples from women with no evidence of cervical intraepithelial neoplasia and 211 (79%) of 266 with cervical intraepithelial lesions or cervical cancer. There was a good correlation between Hybrid Capture and polymerase chain reaction. Hybrid Capture correctly identified 92% of samples found to contain a human papillomavirus type with a high or intermediate oncogenic risk with polymerase chain reaction. Although Hybrid Capture can quantify the amount of human papillomavirus deoxyribonucleic acid present in a sample, no correlation was observed between the relative amount of human papillomavirus deoxyribonucleic acid detected with Hybrid Capture and the grade of cervical lesion. CONCLUSION: The Hybrid Capture test is a sensitive and accurate method for identifying human papillomavirus types of high and intermediate oncogenic risk in clinical specimens.

Cervix Uteri↗

The effect of cervical loop electrosurgical excision on subsequent pregnancy outcome: North American experience.

OBJECTIVE: Our purpose was to determine pregnancy outcome and parturition in women who were treated by loop electrosurgical excision for squamous intraepithelial lesions. STUDY DESIGN: A series of 574 consecutive women of reproductive age (15 to 44 years old) were treated by loop electroexcision for low- and high-grade squamous intraepithelial lesions. The incidence of pregnancies was determined in these women within a 3-year period after therapy by comparing the "observed" number of pregnancies with the "expected" number of pregnancies in the study population, assuming that fertility rates in these women were the same as in the untreated general female population. Pregnancy outcome was correlated in the 53 women who were delivered of an infant with the posttreatment appearance of the cervix and birth weight with maternal smoking. RESULTS: The incidence of pregnancy in the study population was 8.5 per 100 woman years compared with 7.4 per 100 woman years in the untreated central population. Fifty-three women had 54 pregnancies, of which 46 (84%) were live births either at term (40) or between 37 and 39 weeks of gestation (6), and three patients are at present at 24, 34, and 36 weeks of gestation. There were two stillbirths and three first-trimester spontaneous abortions. Premature delivery was not observed. External os stenosis (one case), shortening of the cervix (one case), and repeat electroexcision (four cases) had no adverse effect on pregnancy and parturition. Smoking > or = 10 cigarettes per day before and during pregnancy, rather than loop electrosurgical excision per se, was associated with lower-birth-weight babies than those of nonsmokers (p < 0.01). CONCLUSION: Loop electrosurgical excision to a maximum depth of 1.5 cm and a mean frontal diameter of 1.8 cm does not appear to have adverse effects on subsequent pregnancy outcome and parturition.

Adolescent↗

A polymerase chain reaction-enzyme-linked immunosorbent assay method for detecting human papillomavirus in cervical carcinomas and high-grade cervical cancer precursors.

OBJECTIVE: To develop and evaluate a novel polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA)-based method for detecting high-oncogenic-risk human papillomaviruses (HPV). METHODS: An HPV assay based on PCR amplification of a region of the E6 open reading frame and ELISA detection of PCR products that specifically identify high-oncogenic-risk HPV types (eg, types 16, 18, 31, 33, 35, 39, 45, 56, 58, and 65) was developed. Dacron swabs were used to obtain samples from the cervices of 371 women referred for colposcopy. The swabs were analyzed using the PCR-ELISA method. The results of HPV DNA testing were then compared with the results of a repeat Papanicolaou smear and cervical biopsy obtained at the same visit. RESULTS: The sensitivity of the PCR-ELISA HPV test for detecting invasive cervical cancer or high-grade squamous intraepithelial lesions (SIL) was 90%. High-oncogenic-risk HPVs were detected in six of seven women with biopsy-confirmed invasive cervical cancer, 74 of 81 women with biopsy-confirmed high-grade SIL, 58 of 128 women with biopsy-confirmed low-grade SIL, and 46 of 155 women with no evidence of cervical disease by colposcopy and cervical biopsy. When used in conjunction with a repeat Papanicolaou test, 97% of the women with invasive cervical carcinoma and high-grade SIL lesions were identified. CONCLUSION: The PCR-ELISA-based HPV detection provides the potential for an automated, rapid, and sensitive test for cervical cancer and high-grade cervical lesions.

Base Sequence↗

Treating vaginal and external anogenital condylomas with electrosurgery vs CO2 laser ablation.

Our objective was to assess the technical characteristics, side effects, complications, and effectiveness of electrosurgery vs continuous wave CO2 laser in the treatment of genital warts. This open clinical trial was made up of 208 evaluable patients (135 women and 73 men) with vaginal and external anogenital condylomas. To avoid selection bias, in each patient half of the lesions measuring 2 cm2 or greater total linear area were treated with loop electroexcision and ball electrofulguration, and the other half were treated with CO2 laser excision and vaporization in a continuous wave mode spot welding. All patients were followed for at least 6 months (maximum 18 months, mean 8 months) after the last treatment received. The average operative time was 6 min for electrosurgery and 8 min for laser. Healing was completed in 95% of patients with a lesional area of 5 cm2 or less and 100% of patients with 5 cm2 or larger by the third and sixth postoperative week, respectively. Severe discomfort occurred in 12% of patients, and 4% of patients developed delayed complications, including vitiligo and scarring, irrespective of treatment modalities used. Complete clearance of warts in women and men after a single (51% and 38%) and multiple (75% and 64%) treatments were similar in areas treated with electrosurgery and CO2 laser. Electrosurgery appears to be as effective as continuous wave CO2 laser for treating vaginal and external anogenital condylomas, particularly those limited to a 5 cm2 or less area.

Adult↗

Electroconization of the cervix with a fine-needle electrode.

OBJECTIVE: To obtain electroexcised specimens in which the endocervical margin of the lesional tissue is devoid of thermocoagulation injury, facilitating accurate histologic interpretation of early stromal invasion. METHODS: Using local anesthesia, we performed electroexcision with fine-needle electrodes and a tonsillar snare wire; no sutures to the lateral vessels were required. We tried to obtain cylindrical specimens. The procedure was performed in 38 women with deep canal involvement by squamous intraepithelial lesions, without colposcopically visible endocervical margins. RESULTS: The mean duration of the procedure was 12 minutes (range 8-26). Complications occurred in seven of 38 patients (18%): four cases of perioperative bleeding, one of delayed bleeding, and two of asymptomatic stenosis of the external os. All cases were managed on an outpatient basis. Two cases of unsuspected microinvasive carcinoma were discovered. CONCLUSION: In nonpregnant women in whom the endocervical limit of a lesion cannot be visualized with a colposcope, fine-needle electroconization is an attractive alternative to loop electroexcision. With this technique, cervical specimens can be collected without thermal damage to the endocervical margins.

Adult↗