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The management of genital condylomas, intraepithelial neoplasia, and vulvodynia.

The natural history of HPV-related disease still is poorly understood. Screening of apparently healthy populations suggests that most HPV exposure results only in latent infection; that is, there is no active HPV DNA replication, but the HPV copy number is held at a steady state because viral replication parallels cell division. Unfortunately, knowledge of the cell-virus interaction and the host-immune response has not yet provided an effective medical therapy or a preventive vaccine. Rather, the management of HPV-induced disease remains rooted to the strategy of repeated local destruction. The physician should work methodically through a series of strategic decisions before committing to a management plan.

Carcinoma in Situ↗

Follow-up of atypical glandular cells in cervical-endocervical smears.

Atypical glandular cells of undetermined significance (AGUS) is a diagnostic category of the Bethesda system encompassing glandular-type cells that show either endometrial or endocervical differentiation and display greater atypia than expected for a reactive process but do not meet the criteria for invasive adenocarcinoma. We investigated AGUS in a follow-up study of cervical-endocervical smears with either histology or repeat cytology follow-up. From the cytology files at Northwestern Memorial Hospital over a 4-year period, 136 cervical-endocervical smears were diagnosed with AGUS, which were further subdivided into atypical glandular cells, unqualified (AGC-U); atypical glandular cells, favor reactive (AGC-FR); or atypical glandular cells, favor neoplasia (AGC-FN). Of 96 cases with either histologic or cytologic (cervical-endocervical smear) follow-up, 39 cases of AGC-U had a variety of diagnoses on follow-up, with mostly benign entities in 72% and squamous intraepithelial lesions in 28%. Follow-up of the 36 cases of AGC-FR also demonstrated mostly benign entities (82%) and five cases of squamous intraepithelial lesions. The largest number of premalignant and malignant diagnoses (48%) was found during follow-up of patients with an initial diagnosis of AGC-FN, including the only two cases of adenocarcinoma in situ in our study. In conclusion, our study confirms that AGUS encompasses a wide spectrum of diagnoses, most of which prove to be benign. Subclassification of these cases into "favor reactive" and "favor neoplasia" was found to be helpful in predicting the follow-up status of these patients. However, the small but distinctive percentage of preneoplastic and neoplastic diagnoses seen on follow-up warrant further diagnostic procedures and/or close monitoring in patients with this diagnosis.

Adenocarcinoma↗

[Metaplasia and high grade CIN. Diagnostic difficulties].

Squamous metaplasia of cervix represents the physiologic process of transformation of eversed glandular tissue at external orifice by a malpighian tissue. Primarily undifferentiated and immature, the epithelium progressively becomes differentiated and takes glycogen. In a high grade CIN the normal squamous epithelium is replaced by an undifferentiated tissue comporting basal cells with nuclear atypias. When cellular abnormalities are not marked, differential diagnosis exists with immature metaplasia. Cytology with suspicion of squamous intraepithelial lesion is sometimes followed by a diagnosis of high grade CIN on biopsy, but conisation reveals a metaplasia.

Biopsy↗

Clinical and economic benefit of HPV-load testing in follow-up and management of women postcone biopsy for CIN2-3.

This study aimed to evaluate the clinical and economic implications of integrating human papilloma virus (HPV) load testing into the follow-up and management protocol of women postconisation for high-grade cervical intraepithelial neoplasia (CIN2-3). We evaluated 130 suitable women: 63 were screened biannually by Pap smears ('conventional approach') and 67 also had HPV-load testing ('HPV approach'). More stringent criteria for undergoing colposcopy or reconisation were observed by the former group compared to the latter. Both approaches were analysed for cost effectiveness. There were 33 out of 67 (49.2%) colposcopic referrals and 24 out of 67 (35.8%) reconisation/hysterectomies with the 'conventional approach' compared to 9 out of 63 (14.2%) and 7 out of 63 (11.1%) with the 'HPV approach'. Cervical intraepithelial neoplasia 2-3 residual disease was detected in 7 out of 67 (10.5%) and 7 out of 63 (11.1%) women. The 'conventional approach' had more negative colposcopic biopsies and more negative reconisation/hysterectomy histologies than the 'HPV approach'. The respective cost per detection of one case of residual disease was US$3573 and US$3485. The 'HPV approach' required fewer colposcopic and reconisation procedures to detect one case of residual CIN2-3. Its higher positive predictive value than that of cytology provided a significant decrease in false positive rates and a reduction of US$88 per detected case.

Adolescent↗

Outpatient management of abnormal smears.

OBJECTIVES: To review the results of the first 403 women treated at the Abnormal Smear and Colposcopy Unit with special reference to the utility, efficacy, acceptability and economy of in-office treatment of cervical lesions by large loop or Fischer cone excision. DESIGN: Retrospective chart review of consecutive patients treated following, referral with an abnormal smear or abnormal cervical morphology, between 1 September 1996 and 1 August 2001. SETTING: Inner city private practice. SAMPLE: A total of 403 consecutive General Practitioner referred women. METHODS: Details of referral smear result, colposcopically directed biopsy result, subsequent treatment type and histological result including assessability, number of specimens submitted, complications and follow-up assessment were extracted at chart review. Costs of public hospital inpatient and outpatient care, supplied by the Casemix and Clinical Benchmarking Service, Mater Miseraecordae Public Hospitals (with permission to publish), were compared with Medicare rebates. MAIN OUTCOME MEASURES: A total of 187 women were treated by large loop excision of the transformation zone, and 216 by Fischer cone excision. The number of women who were treated as outpatients under local anaesthetic were 395, while eight patients were treated under general anaesthesia as inpatients. There was poor correlation between referring smear, biopsy and subsequent treatment results. Eight patients had abnormal cytology at follow-up, of whom two have been retreated. Three patients had primary or secondary bleeding requiring treatment and two developed cervical stenosis. Outpatient private practice treatment of women with abnormal smears allows significant savings to the public purse over public or private hospital care. CONCLUSIONS: Outpatient treatment of women with abnormal smears, using the Fischer cone technique, is safe, well accepted, effective and the most cost efficient solution to this public health problem.

Ambulatory Care↗

The correlation between the grade of dyskaryosis on cervical smear, grade of cervical intraepithelial neoplasia (CIN) on punch biopsy and the final histological diagnosis on cone biopsies of the cervix.

This study was carried out to assess how reliably a punch biopsy of the cervix predicts the maximum grade of CIN present and whether a colposcopically directed punch biopsy is more reliable than cytology in predicting the grade of intraepithelial neoplasia present in the cervix. The grade of CIN in 107 cone biopsy specimens was compared with the grade of CIN and dyskaryosis in punch biopsies and smears from the same patients. Exact correlations were identified between the highest grade lesions on cone biopsy and those in 63% of punch biopsies and 49% of cervical smears. We conclude that punch biopsy provides a more reliable estimate of the highest grade of CIN present in a subsequent cone biopsy than cervical cytology, but nonetheless fails to give a consistent estimate of the final grade of CIN in a significant percentage of cases.

Biopsy↗

[The Bethesda system--an improvement in classification of cervix cytology?].

Cervical cytology screening programmes have significantly reduced cervical cancer mortality. In 1988 the National Cancer Institute developed a new classification for reporting cervical cytology--"The Bethesda System". The aim of our study was to compare the clinical usefulness of this new classification with the classification used in German-speaking countries (which discriminates cytologically between moderate and severe dysplasia) including a verbal classification predicting the histological grade of cervical intraepithelial neoplasia (CIN I, II, III). 671 patients with abnormal cervical cytology results and subsequent conisation or hysterectomy were included. We correlated cytological and histological diagnosis (gold standard). In cases of cytologically suggested moderate dysplasia we found histologically CIN I, CIN II and CIN III in 11%, 41% and 42%, respectively. Our results show that discrimination of CIN II and CIN III by means of cytology is limited. Using our therapy schedules we found that adequate therapy is possible by each of the cytological classification systems. The cervical smear is used as a screening test to determine which women require further examination using colposcopy. Under these circumstances an adequate therapy is possible with both classifications. The results underline the importance of colposcopy in the management of cervical dysplasia. As long as conisation is commonly used in German-speaking countries as the only diagnostic tool after an abnormal cervical smear the Bethesda System increases the risk of overtreatment.

Adult↗

The effects of loop excision of the transformation zone on cervical length: implications for pregnancy.

OBJECTIVE: This study was undertaken to determine whether previously described significant and quantitative cervical shortening caused by loop excision of the transformation zone persists after 3 months of healing. STUDY DESIGN: A prospective study was designed in which 20 patients were enrolled. Each underwent transvaginal ultrasonography for determination of cervical length before the loop excision of the transformation zone and >/=3 months after the loop excision of the transformation zone. Simple regression analysis and the Student paired t test was performed to determine whether the length of the cervix had changed significantly between the measurements. RESULTS: The mean cervical lengths as measured by transvaginal ultrasonography before and after loop excision of the transformation zone were 3.1 +/- 0.8 cm and 3.1 +/- 0.7 cm, respectively. The correlation between ultrasonographic measurements before and after loop excision of the transformation zone was r = 0.88 (P <.0001). A paired t test resulted in a P value of 1.0000, which indicates that the ultrasonographic measurement after loop excision of the transformation zone was not different from the ultrasonographic measurement before loop excision of the transformation zone. The mean difference between measurements was 0.0 +/- 0.4 cm. CONCLUSION: After adequate healing time after loop excision of the transformation zone, the length of the cervix, as measured by transvaginal ultrasonography, does not appear to remain shortened.

Cervix Uteri↗

Effect of excisional therapy and highly active antiretroviral therapy on cervical intraepithelial neoplasia in women infected with human immunodeficiency virus.

OBJECTIVE: Our purpose was to determine the rates of recurrence, persistence, and progression of cervical intraepithelial neoplasia in women who were seropositive for human immunodeficiency virus after excisional therapy with and without highly active antiretroviral therapy. STUDY DESIGN: The records of 118 women with cervical intraepithelial neoplasia, 56 of whom were infected with human immunodeficiency virus and 62 of whom were not infected, were examined to compare outcomes. Demographic, behavioral, and clinical indices were analyzed. RESULTS: Of 54 women infected with human immunodeficiency virus, 31 (57.4%) had persistent or recurrent cervical intraepithelial neoplasia, in comparison with 10 (16.7%) of 60 noninfected women (P <.01). Progression occurred in 4 (16.7%) of 54 in the infected group and in 3 (5.0%) of 60 in the noninfected group (P <.05). In 21 (60.0%) of 35 infected women, in comparison with 8 (32%) of 25 noninfected women, disease persisted 6 months after diagnosis if treatment was not given (P <.05). Of 19 infected women, 10 (52.6%) had recurrent disease after treatment, compared with 2 (5.7%) of 35 noninfected women (P <.01). Risk factors for recurrence in women who were seropositive for human immunodeficiency virus included margin involvement of specimens obtained by loop electrosurgical excision (87.5% vs 20.0%l; P <.05). Exposure to highly active antiretroviral therapy, including therapy with protease inhibitors, was associated with a lower recurrence or persistence rate (17.6% vs. 70.3%; P <.05) and a lower progression rate (0% vs. 24%; P <.05). CONCLUSION: Women infected with human immunodeficiency virus had high rates of recurrent and persistent cervical intraepithelial neoplasia despite standard therapy. Low CD4(+) levels and margin involvement of specimens obtained by loop electrosurgical excision are risk factors for recurrence. The use of highly active antiretroviral therapy is associated with a lower risk of recurrence, persistence, and progression of cervical intraepithelial neoplasia.

Adult↗

2001 consensus guidelines for the management of women with cervical intraepithelial neoplasia.

OBJECTIVE: The study was undertaken to provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN) that can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age. PARTICIPANTS: An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology (ASCCP). CONSENSUS PROCESS: Guidelines for the management of women with CIN were developed through a multistep process. Draft management guidelines were developed by working groups who performed formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the ASCCP Consensus Conference, September 6 through 8, 2001, in Bethesda, Md, all guidelines were discussed, revised, and adopted by formal vote. CONCLUSION: Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN.

Biopsy↗

Abnormal Pap smears: a comparison of total abdominal hysterectomy and cone biopsy in management.

A recent study found that colposcopy is still not available to over 50% of gynaecologists practicing in Nigeria and that 91% of them will do either cone biopsy or hysterectomy for moderately or severely abnormal Pap smears. Currently, there are no local data to guide such patient care. In order to compare cone biopsy and hysterectomy in terms of their pick-up rates of cervical intraepithelial neoplasia and invasive cancer in women with abnormal pap smears, a retrospective review of entries in the histology reports of all cases of cone biopsy and hysterectomy done for abnormal Pap smears from 1975-2004 at the histopathology department of the University of Nigeria Teaching Hospital, Enugu, Nigeria, was carried out. The study revealed that 203 women with moderately to severely abnormal Pap smears were treated with either cone biopsy or hysterectomy. A total of 88 (43.3%) women had cone biopsy, while the remaining 115 (56.7%) had total abdominal hysterectomy. Those who had cone biopsy were significantly younger than those who had hysterectomy (mean ages: 44.6+/-8.8 vs 52.3+/-9.8 years; p=0.008). There was no significant difference in parity between those who had cone biopsy and those who had hysterectomy (mean parity: 5.7+/-2.3 vs 6.5+/-2.2; p=0.102). For all the 203 women, the histology was reported as normal in 97 (47.8%) women and inflammatory in six (3.0%). The three cases of invasive cervical carcinoma were found in women with moderately abnormal Pap smears. One had a cone biopsy, while the other two had a simple total abdominal hysterectomy. Cone biopsy and hysterectomy did not differ significantly in their pick-up rates of the various categories of cervical lesions including invasive carcinoma (p>0.05 for all categories). It was concluded that cone biopsy and hysterectomy have similar pick up rates for the various types of cervical lesions. For this reason, in the absence of colposcopy as occurs in many parts of the developing world, cone biopsy may be adequate treatment and should be offered first to women with moderately to severely abnormal Pap smears.

Adult↗

The status and distance of cone biopsy margins as a predictor of excision adequacy for endocervical adenocarcinoma in situ.

Cervical cone biopsy has become an important surgical procedure for endocervical adenocarcinoma in situ (AIS), especially for patients who desire to retain their fertility. Establishing the usefulness of the endocervical margin status in cone biopsy specimens as a predictor of residual AIS is paramount. We examined the status of the endocervical margin in the cone biopsy specimen, the distance between the most proximal AIS and the endocervical margin in the cone biopsy specimen, and the endocervical curettage (ECC) specimen performed at the time of cone biopsy and residual AIS in the hysterectomy specimens of 61 patients with specimens accessioned from 1968 through 1997; 43 (30%) of patients with a negative endocervical margin had residual AIS in the hysterectomy specimen. Conversely, 10 of 18 (56%) patients with a positive endocervical margin in the cone biopsy specimen had no AIS in the hysterectomy specimen. All 6 patients with AIS in the ECC specimen had residual AIS. No patient with an endocervical margin in the cone biopsy specimen greater than 10 mm had residual AIS. Patients with distances less than 10 mm had equal percentages of residual AIS. In general, more patients with a negative endocervical margin in the cone biopsy specimen had no residual AIS in the hysterectomy specimen than those with a positive endocervical margin in the cone biopsy specimen. However, the status of this margin is not useful for predicting the presence of residual AIS. Pathologists should report the distance between the endocervical cone biopsy margin and the closest AIS.

Adenocarcinoma↗