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Randomized study comparing two techniques of conization: cold knife versus loop excision.

OBJECTIVE: To compare the histomorphologic and colposcopic results of cold knife conization and loop excision. METHODS: Sixty-six women were randomly allocated to have the cone specimen removed by cold knife excision (n = 38) or loop excision (n = 28). Subjects eligible for inclusion were those who presented histologically verified grade 3 cervical intraepithelial neoplasia (CIN) or grade 2 CIN with squamocolumnar junction not seen. RESULTS: The mean height of the cone specimens was greater in the cold knife group [18.9 mm (SD = 5. 5) and 12.8 mm (SD = 4.3), respectively; P = 0.0001], as was the frequency of clear margins (100 and 80%, respectively; P = 0.001). In the loop excision group, thermal injuries were present in half of the cone sections. The median (range) thickness of thermal injury was 0.98 mm (0-1.5 mm) in the ectocervix and 0.95 mm (0-1.75 mm) in the endocervix. Histologic evaluation of the endocervical margins was not possible in 2 cases (7%). At follow-up colposcopy, evaluation of the entire squamocolumnar junction was possible in 15 (39%) and 20 (71%) women, respectively (P < 0.01). Four patients in the cold knife group and 6 in the loop group had histologically confirmed persistent dysplasia (P > 0.05), yielding success rates of 90 and 79%, respectively (P > 0.05). CONCLUSIONS: Loop excision provides a sample that is adequate for histologic evaluation in most cases, results in the same success rate as cold knife conization, and allows optimal colposcopic surveillance in significantly more cases than cold knife excision.

Adult↗

Biopsy correlates of abnormal cervical cytology classified using the Bethesda system.

OBJECTIVE: The goal of this study was to determine the colposcopic findings underlying cytologic abnormalities classified according to the Bethesda system. METHODS: Women undergoing colposcopy for abnormal cytology at an urban teaching hospital between July 1, 1996 and December 31, 1999 had Papanicolaou smears repeated. Results were compared both with biopsy histology and with the worst histology reported after 8-26 months of follow-up. kappa statistics and Spearman's rho were calculated to determine the degree of agreement. RESULTS: Colposcopy was performed for 2263 (94%) women. Referral and repeat Pap smears were reported identically in 493 (25%) of the 1962 women with results for both. No AGUS (atypical glandular cells of uncertain significance) smears were confirmed on repeat smear, and after excluding AGUS, agreement within one grade was found in 1305 of 1854 (70%). Among the 1842 women with squamous cytologic abnormalities, biopsy revealed a lesion more severe than that suggested by referral cytology in 577 (31%) and a less severe lesion in 648 (35%); exact correspondence was found in only 646 (35%). Of 317 women with ASCUS (atypical squamous cells of uncertain significance) on referral Pap smear, a negative repeat smear, and a specific biopsy result, 95 (30%) had true negative histology, while 148 (47%) had condyloma, 56 (18%) had cervical intraepithelial neoplasia (CIN) 1, 8 (3%) had CIN 2, 10 (3%) had CIN 3, and none had cancer. Comparison of repeat smear and colposcopic biopsy yielded a kappa statistic of 0.16. CONCLUSIONS: Cytology classified according to the Bethesda system does not accurately predict histologic diagnosis.

Adolescent↗

Detection of transforming gene regions of human papillomavirus type 16 in cervical dysplasias by the polymerase chain reaction.

In a study of 29 cases of histologically confirmed, characterized colposcopically and cytologically, cervical intraepithelial neoplasias 48.3% (14/29) of biopsies were positive for human papillomavirus (HPV) type 16 DNA by polymerase chain reaction. We used two oligonucleotide primer pairs (position 215-514 and 606-805) flanking a 300 and a 199 base pair fragment from the early 6 (E6) and early 7 (E7) genes. The results were concordant both with the E6 and with the E7 regions. Of the amplified products 85.7% (12/14) could be confirmed; these carried 16 specific sequences by Southern blot hybridization. HPV 16 DNA was present in 6.7% (2/30) of the colposcopically directed cytologically normal matched control samples using the same methods.

Adult↗

Oral contraceptive use and human papillomavirus infection in women without abnormal cytological results.

Both experimental and epidemiological data support the idea that oral contraceptive (OC) use may have a stimulating effect to a certain point on cervical carcinogenesis. The current investigation tries to answer the question whether OC use might have an influence on early human papillomavirus (HPV) infections. A total of 425 women without abnormal cytological results were examined colposcopically, and filter in situ hybridisation (FISH) was used to determine the presence of human papillomavirus (HPV) types 6, 11, 16 and 18. Eighty-one cervical specimens (19.1%) were found to be positive for one or more of the HPV types in FISH. HPV positivity was found to correlate with age and parity, being the highest among women under 25 and with less than two births. The use of OCs was inversely correlated with the presence of ectopy or dysplasia in this group of women. On the other hand, HPV positivity was not significantly higher among OC users than among non-users in any colposcopic group. Neither the type of pill used, nor the duration of use had any significant effect on HPV positivity. Further investigations are needed to evaluate the effects of OC use on more severe HPV-induced cervical lesions.

Age Factors↗

Diagnosis of cervical intraepithelial neoplasia and human papillomavirus infection: punch biopsy versus cervical smear.

In 102 patients referred to our colposcopy clinic because of one to three Papanicolaou smears indicating cervical intraepithelial neoplasia (CIN) and/or abnormal colposcopy, routine smears and colposcopically directed punch biopsies were taken simultaneously. For detection and typing of human papillomavirus (HPV)-DNA in situ hybridization was performed in all biopsies and in 46 of the cervical smears. In cases of dysplastic lesions the number of HPV 16/18 (40.5%) and 31/33 (42.9%) was markedly higher than HPV 6/11 (16.6%) infection rate. In cases where simultaneous in situ hybridization in biopsy specimen and cervical smears was performed 21.7% showed a HPV negative smear and a positive biopsy, in 6.5% the results were the other way round. In 34.9% of cases with CIN I and 9.5% of cases with CIN II verified by punch biopsy the cytological smear did not indicate dysplasia. Our data show that mild and moderate CIN lesions of the cervix as well as HPV infection are detected more frequently by a combination of cervical smear and colposcopically directed punch biopsy than by cervical smear alone.

Biopsy↗

Spermicidal activity of a new contraceptive sponge.

An open, crossover study evaluated the spermicidal efficacy and irritative potential of the Protectaid sponge. Postcoital tests were conducted in nine healthy couples under control conditions (no sponge) and with the sponge. Microscopic examination of postcoital mucus from the female partners showed that sperm entered the cervix in all nine controls, whereas entry was completely prevented by the sponge in four of nine women. None of the participants showed colposcopic evidence of mucosal irritation while using the sponge. Colposcopic abnormalities were evident in two of nine women during control testing. The urgent need for female-controlled contraceptive methods with the potential to protect against sexually transmitted diseases makes this low-dose spermicidal vaginal sponge an effective and safe alternative.

Adolescent↗

Cancer risk in diethylstilbestrol-exposed offspring.

The occurrence of columnar epithelium in the vagina (vaginal adenosis) in young women with intrauterine exposure to diethylstilbestrol (DES) during the first trimester of pregnancy was observed in 231 patients (82 per cent of 280 cases who underwent colposcopic study). Extension of columnar epithelium onto the portio of the cervix was present in the remaining 18 per cent of the cases. Abnormal colposcopic findings were present in the transformation zone in 96 per cent of the patients with vaginal adenosis. Directed biopsy revealed four cases of vaginal and/or cervical squamous carcinoma in situ (CIS), two cases of severe dysplasia, five cases of moderate, and 29 cases of mild dysplasia. The prevalence of CIS in DES-exposed girls (1.4 per cent) was nearly five times the prevalence rate of CIS in a control group of 5,808 DES-unexposed women (0.44 per cent). This finding correlates well with the hypothesis that the genesis of squamous intraepithelial neoplasia is specifically related to the extent and surface area of the vaginal transformation zone. An unusual case of invasive squamous carcinoma in a DES-exposed young girl is presented, which represents the initial observation of this association to date.

Adolescent↗

Vaginal intraepithelial neoplasia: Biologic aspects and treatment with topical 5-fluorouracil and the carbon dioxide laser.

A review of 41 evaluable patients was made in order to study vaginal intraepithelial neoplasia (VAIN) and to investigate new methods of treatment. Colposcopic examination of the vagina revealed white epithelium alone in 20 patients and white epithelium associated with vascular punctation in 15. No lesion had a vascular mosaic pattern. Most patients had multifocal disease located in the vaginal apex. Iodine staining was positive in six patients with negative colposcopic examinations. Twenty-four patients had severe dysplasia or carcinoma in situ, and 17 had minimal or moderate dyplasia. Associated genital disease occurred in 17 patients with antecedent cervical or vulvar squamous neoplasia, and six additional patients had coexistent lesions. The chronology of vaginal disease that appeared after treatment of cervical neoplasia suggests a persistent but decreasing likelihood of the development of VAIN with the passage of time. In patients followed without therapy, six had spontaneous remission of disease. Treatment was successful in 12 of 15 patients with topical 5-fluorouracil and in nine of 10 patients with the carbon dioxide laser. The advantage of these methods of treatment for patients with VAIN relative to surgical procedures and radiation therapy are considered.

Adult↗

The significance of atypical vessels and neovascularization in cervical neoplasia.

The relationship between atypical vessels seen colposcopically and dysplasia, carcinoma in situ (CIS), microinvasion, and frank invasion was studied quantitatively. No atypical vessels were found with dysplasia, but 2.8% of patients with CIS had atypical vessels. Half of the patients with microinvasion and all of the patients with frank invasion, in whom the entire zone of transformation was viewed, had atypical vessels. Eight-two percent of the patients with atypical vessels had invasion. The conclusions are: (1) Atypical vessels are not present with dysplasia and rarely present with CIS. (2) Atypical vessels may be associated with microinvasion, but are required for frank invasion to occur. (3) Because atypical vessels are usually associated with invasion, which can be in or near the field of atypical vessels, diagnosis cone biopsy should be performed if atypical vessels are seen and colposcopic biopsies do not show frank invasion. (4) Microinvasion without atypical vessels may be a localized disease.

Adult↗

Treatment of cervical intraepithelial neoplasia with the carbon dioxide laser.

The carbon dioxide laser was used to treat 138 patients with cervical intraepithelial neoplasia between February, 1979, and February, 1981. All patients in this study were assessed in the colposcopy clinic prior to treatment. The diagnosis of cervical intraepithelial neoplasia was based on colposcopic examination, cytologic findings, colposcopically directed biopsy, and endocervical biopsy in all cases. Included in the 138 patients were 26 with grade 1, 82 with grade 2, and 30 with grade 3 cervical intraepithelial neoplasia. The persistence rate of abnormal cytologic findings at 7 months after treatment was 11% for grade 1, 8.5% for grade 2, and 10% for grade 3 cervical intraepithelial neoplasia. No major complications accompany this treatment modality, which was performed in the outpatient clinic without the use of anesthesia or analgesia.

Adult↗

Atypia in cervical cytology as a risk factor for intraepithelial neoplasia.

All Papanicolaou smears obtained during the years 1977 to 1982 were reported by a descriptive cytologic interpretation instead of a numerical report. All smears showing "atypia" were reviewed and found to fall into one of three categories: inflammatory atypia, squamous atypia, and endocervical atypia. Patients with the latter two categories and those with persistent inflammatory atypia after specific therapy underwent colposcopy and directed biopsies if indicated. Colposcopically directed biopsies revealed that 29% of patients with atypical Papanicolaou smears had underlying cervical intraepithelial neoplasia. There was no statistically significant difference in the incidence of underlying cervical intraepithelial neoplasia among patients in each of the three categories of atypia. Of those with intraepithelial neoplasia, 35% had lesions of greater severity than grade 1 cervical intraepithelial neoplasia. We conclude that all patients with squamous, endocervical, and persistent inflammatory atypia on Papanicolaou smear should undergo colposcopic evaluation to rule out intraepithelial neoplasia.

Adult↗

Evaluation of the effects of a female condom on the female lower genital tract.

The purposes of this study were to determine if use of the female condom (Reality) was traumatic to the vaginal mucosa and/or vulvar skin and to determine its effect on resident vaginal bacterial flora. Thirty subjects were randomly assigned to utilize the female condom or diaphragm during the study period. Initially and during 3 follow-up visits, each subject underwent colposcopic examination of the vagina, cervix, and vulva with photographic record, and qualitative fungal, aerobic and anaerobic cultures of the vagina. The two groups were compared with respect to the frequency of abnormal physical findings determined by both macroscopic and colposcopic examination. Visits were compared within each contraceptive group with respect to changes in resident vaginal flora. There was no evidence of significant trauma associated with the use of either contraceptive device during the study period. The resident vaginal flora did not significantly change during the three follow-up visits in patients using the female condom. In diaphragm users, lactobacilli were less frequently isolated at the third (14/15 vs 6/15, P = 0.008) and fourth (14/15 vs 7/15, P = 0.039) follow-up visits when compared to the initial visit. In addition, aerobic gram-negative rods were more frequently isolated during the fourth visit (1/15 vs 9/15, P = 0.021) when compared to the first visit. We conclude that neither the female condom (Reality) nor the diaphragm is associated with trauma to the lower genital tract. Subjects using the diaphragm undergo a significant change in vaginal bacterial flora, becoming more likely to be colonized with coliform microorganisms and less likely to maintain lactobacilli colonization.

Adult↗

The diagnosis and management of cervical intraepithelial neoplasia in the patient under the age of twenty-one.

The diagnosis and management of 260 patients between the ages of 15 and 21 with cervical intraepithelial neoplasia is discussed. These patients represented 22% of all new patients seen in the Colposcopy Clinic of The Johns Hopkins Hospital between January 1975 and December 1979. Sixty-six percent of the patients were referred for evaluation of two Papanicolaou smears which were compatible with the diagnosis of CIN I while only 1.5% of the patients were referred with the cytologic diagnosis of CIN III. The colposcopic impression in the majority of patients was CIN I. There was excellent correlation between the colposcopic impression and histopathology. Thirteen percent of the patients evaluated had surgical procedures, 11% (29 patients) under-went conization and 2% (five patients) hysterectomy. The majority of patients under the age of 21 had minimal degree of cervical intraepithelial neoplasia. The importance of conservative management is discussed.

Adolescent↗

Cervical intra-epithelial neoplasia in pregnancy.

A retrospective analysis of 110 cases of suspected cervical intra-epithelial neoplasia (CIN) associated with pregnancy seen at the State University of New York at Buffalo (SUNYAB) affiliated hospitals is the subject of this report. One hundred anf five patients had abnormal cytology and five had negative pap smears. The majority of patients (60%) were in their twenties, and 24% were primigravidas. Colposcopic examination with or without directed biopsy eliminated the need for conization in 104 of 107 patients. Only two patients had to have cone biopsy and one had a modified conization after colposcopically directed biopsies. Varying degrees of cervical intra-epithelial neoplasia (Grades I-III) were diagnosed in 55 cases. One patient had therapeutic conization and two with a poor follow-up history had cesarean section hysterectomies. Post pregnancy regression of CIN was documented in 20 cases and persistence in 19 cases. The literature is surveyed and the management of CIN in pregnancy is discussed.

Adolescent↗

Postpartum colposcopy of the cervix: injury and healing.

Colposcopic examination was done in 189 successive parturients within 6-48 h of delivery for evidence of type, site, and extent of cervical trauma and its relation to various obstetric factors. There was trauma in 66% of cases, as erosion in 79%, as laceration in 56%, as bruising in 30%, and as yellow areas in 17%. In about two-thirds of cases, the diameter of cervical erosion, or the length of laceration did not exceed 5 mm and 81% of lacerations were of first degree. Cervical injury was significantly more frequent in primiparae, in the anterior cervical lip, in occipito-posterior positions, and with premature rupture of membranes. In 117 parturients with cervical injury another colposcopic examination was done 6-8 weeks postpartum. In 8% there was residual cervical damage.

Adult↗

Cytohistology, colposcopy and in situ hybridization in cervical preneoplastic lesions: a correlative study.

Formalin-fixed, paraffin-embedded cervical tissues from 106 patients which exhibited a colposcopically atypical transformation zone, were examined for the presence of HPV DNA by in situ hybridization using biotin-labeled HPV 6/11 and 16/18 DNA probes. From the comparative study between histologic, cytologic, colposcopic findings and virologic results it is confirmed that HPV 6/11 DNA is detected more frequently in the less severe lesions, whereas HPV 16/18 DNA is predominantly found in the most severe dysplastic lesions.

Cervix Uteri↗

Microglandular hyperplasia--a complicating factor in the diagnosis of cervical intraepithelial neoplasia.

Cervical microglandular hyperplasia is an unusual lesion that may confused with malignancy, by both macroscopic and colposcopic examinations. Even the cytologic and histologic characteristics may mimic an adenocarcinoma. When, in addition, the simultaneous occurrence of an area of cervical intraepithelial neoplasia is found, it could complicate the correct diagnosis. The clinical implications are discussed on the basis of a single case and the available literature survey. We suggest an in-depth colposcopic and histopathologic examination prior to making a definite diagnosis.

Adenocarcinoma↗

Test of immunopotentialization in colposcopy--a clinical evaluation.

52 infertile women (age range 19-35 years) treated by Gynatren-immunopotentialization (three vaccinations every second week) were divided into two groups according to appearance of cervical intraepithelial neoplasia (CIN). 30 women had CIN cytologically diagnosed and proved by colposcopy (group II). Colposcopic examinations were performed on the first day of therapy (first vaccination), after two weeks (second vaccination) and after four weeks (the day of the third injection). Four weeks of the therapy resulted in normalization of cervical milieu (e.g., complete regression of infection in 68.2% of I group and 56% of II group) as well as in disappearance of CIN in 66% of cases and in remaining ones there was a 7-times decrease of CIN II. It was colposcopically stated that the process of statistical significant regression of inflammation as well as normalization of cervical pathology is less apparent in women with CIN. These findings confirmed our previous cytological observations.

Adjuvants, Immunologic↗