Cytologic detection of condylomas and cervical intraepithelial neoplasia of the uterine cervix with histologic correlation

Human papillomavirus (HPV) has been implicated as an important etiologic factor in cervical carcinoma. This study evaluates the efficacy of cytology as a screening tool in the detection of cervical lesions with koilocytotic features. Cervical smears and biopsy specimens from 76 women seen between January 1983 and October 1985 were reviewed. The histologic categories consisted of koilocytotic lesions (flat condylomas) with minimal cellular atypia, CIN I, II, III, with surface koilocytes showing cellular atypia (atypical koilocytosis), CIN III with a contiguous lesion as defined in categories 1 and 2, negative biopsies. Histologically, five cases showed flat condylomas with minimal cellular atypia, 65 showed cervical intraepithelial neoplasia (CIN) with atypical koilocytosis and two showed negative biopsies. Cytologically, in all cases of flat condyloma with minimal cellular atypia (5+5), CIN I with atypical koilocytosis (39/39), and CIN III with a contiguous condylomatous lesion (4/4) both koilocytes and, in the latter two categories, dysplastic cells were identified in the cervical smears. In 7/9 cases of CIN II and 9/17 cases of CIN III with atypical koilocytosis, smears showed both atypical koilocytes and dysplastic cells. In the remaining ten cases, however, there was cytologic underestimation of the histologic diagnosis of CIN, particularly when the lesion was focal. The data suggests that although cytology does detect a high percentage of cervical lesions with koilocytotic features (64/76, 84% in this study), it may not detect focal CIN II, CIN III lesions associated with condylomatous lesions in the same biopsy specimen. Therefore, it is proposed that all women with cytologic evidence of koilocytosis on cervical smears are deserving of a colposcopic examination.     

Atypical glandular cells of undetermined significance: clinically significant lesions and means of patient follow-up

BACKGROUND: The clinical significance of atypical glandular cells of undetermined significance (AGUS) remains poorly understood, and patient management is not standardized. The authors evaluated the rate, qualification, and follow-up (FU) findings of AGUS patients. METHODS: Computerized records from the authors' institution were searched from April 1992 to December 1997 for diagnoses of AGUS. Results of cytologic and histologic FU were evaluated up to 48 months of FU. Clinically significant lesions were defined as squamous intraepithelial lesion (SIL), endometrial pathology of hyperplasia or higher, adenocarcinoma in situ (AIS), or invasive adenocarcinoma. RESULTS: AGUS was diagnosed in 92 of 87,632 patients (0.11%). FU data were available from 69 patients, consisting of smears and/or surgical pathology specimens from the cervix, endometrium, or ovary. Forty patients had FU smears only, 13 had histologic FU only, and 16 had both. Seventeen patients (25%; 15 patients with unqualified AGUS and 2 patients with "favor endometrial origin" according to the Bethesda System of AGUS subclassification) had clinically significant lesions: high grade SIL (n = 8 patients), low grade SIL (n = 2 patients), endometrial lesion (n = 5 patients), AIS (n = 1 patient), and invasive cervical adenocarcinoma (n = 1 patient). It is noteworthy that 4 patients with carcinoma (3 patients with AIS and 1 patient with invasive carcinoma) were diagnosed after a long FU (36-48 months). The remaining 13 lesions were detected at first FU (1-24 months). Six lesions were detected on FU smear, whereas 15 were detected histologically (4 lesions were detected in both). CONCLUSIONS: AGUS is associated with clinically significant lesions in 25% of patients who are followed. Most of the lesions were high grade and were detected histologically. Moreover, 4 of 17 lesions were detected after a FU period ranging from 36 months to 48 months. The role of qualifying AGUS needs further study. Cancer (Cancer Cytopathol) Copyright 2000 American Cancer Society.     

Prevalence of Abnormal Pap Smears: A Descriptive Study from a Cancer Center in a Low-Prevalence Community

Background and aims: Cervical cancer is the fourth most common cancer in women worldwide and the 13th in Jordan. The cervical smear (Pap smear) is a simple approach to detect pre-cancerous cervical lesions. The aim of this study was to evaluate the prevalence of abnormal cervical smears in women seen at the Early Detection/Community Outreach clinic of King Hussein Cancer Center (KHCC). Materials and Methods: In this retrospective study, reports of routine cervical Pap smears performed in the pathology department at KHCC from January 2007 to December 2016, were reviewed. During this period, a total of 5,529 routine smears were assessed for epithelial abnormalities and histopathological grading. Results: A total of 210 (3.8%) abnormal Pap smears were found, with atypical squamous cell of undetermined significance (ASC-US) reported in 110 (52.4%) cases, atypical glandular cells of undermined significance (AGUS) in 58 (27.6%), low grade squamous intra-epithelial lesion (LSIL) in 27 (12.9%) and high grade intra-epithelial lesion (HSIL) in 13 (6.2%). Only single cases of ASC-H and squamous cell carcinoma were reported. The available biopsies showed benign findings in 70.1% of cases, low grade squamous intraepithelial lesions in 11.5% and high grade squamous intraepithelial lesions in 18.4%. Conclusions: The low epithelial cell abnormality (EPCA) prevalence illustrated in this study argues against introduction of population-based HPV testing and vaccination. It calls for a more cost-effective measures in a country with limited resources, where a more widely available Pap-smear testing might suffice.     

Association of Abnormal Pap Smear with Occult Cervical Stromal Invasion in Patients with Endometrial Cancer

Objective: The purpose of this study was to determine the association between abnormal preoperative Pap smearresults and occult cervical stromal invasion in endometrial cancer patients. Methods: Medical records were reviewed ofpatients with endometrial cancer who had undergone surgical staging at Srinagarind Hospital. Patients with gross cervicalinvolvement, with an unsatisfactory Pap smear, without available Pap smear results, with no cervical intraepitheliallesion/invasive cervical cancer, or who had previously undergone pelvic radiation therapy were excluded. The patientswere assigned to one of two groups according their Pap smear results (negative and epithelial cell abnormalities).Logistic regression was used to determine the independent association between an abnormal Pap smear and the riskof cervical stromal invasion. Results: All cervical smears in this study were performed as conventional Pap smears.Smears were abnormal in 50 (21.0%) of the 238 patients enrolled and normal in the remaining 188 (79.0%). The typesof Pap smear abnormalities included adenocarcinoma (n=22); atypical endometrial cells (n=2); atypical glandular cells(n=17); high-grade squamous intraepithelial lesions (n=4); atypical squamous cells, cannot exclude high-grade squamousintraepithelial lesions (n=2); and atypical squamous cells of undetermined significance (n=3). After controlling for type ofendometrial cancer, abnormal Pap smear results were found to be a significant independent factor that indicated cervicalstromal invasion (adjusted OR 2.65; 95% CI 1.35 to 5.21). Conclusion: Endometrial cancer patients with abnormalPap smears were strongly and independently associated with histopathologically diagnosed cervical stromal invasion.     

A comparison of liquid-based cytology and Pap smear as a screening method for cervical cancer

The implementation of population-based screening for cervical cancer with Pap smear in the early sixties was set to detect and treat precancerous lesions, hopefully preventing a subsequent invasive cervical cancer. Epidemiological data indicate that organized screening has a major impact on morbidity and mortality from cervical cancer. The limited sensitivity of a single smear necessitates repeated smears in organized program. It is suggested that liquid-based cytology improves the sensitivity. The aim of this split-sample study was to compare ThinPrep liquid-based cytology with conventional Pap smear, relying on a laboratory with long-term experience of the latter. In total, 137 women with atypical Pap smear in population-based cervical screening were enrolled for the split-sample study. The performance of both techniques (ThinPrep liquid-based cytology and conventional Pap smear) were compared and validated by a histological follow-up. Women without representative histological biopsy were excluded from the study. Pap smear had sensitivity for detection of CIN2-3 of 47% compared to 66% for liquid-based material. The concordance of the two sampling techniques with the histological diagnosis was 37% and 53%, respectively, this difference being statistically significant. The proportion of reports on atypical squamous cells of undetermined significance (ASCUS) was significantly less in the liquid-based material, 4.3% compared to 8% of the conventional smears. This improved sensitivity in combination with the possibility to perform reflex testing such as HPV DNA or p16 immunocytochemistry without renewed sampling gives ThinPrep a substantial advantage and makes the liquid-based technique interesting.     

Can Adenocarcinoma in situ of the Uterine Cervix be Predicted before Cervical Conization?

This study was undertaken to determine the effectiveness of the Papanicolaou (Pap) smear, colposcopicallydirectedbiopsy (CDB), and endocervical curettage (ECC) in preconization detection of adenocarcinoma in situ (AIS)of the uterine cervix. Women, whose cervical conization specimens contained adenocarcinoma in situ without anyassociated invasive lesion at Chiang Mai University Hospital between March 1998 and March 2006, were reviewed.During the study period, fifty-one women who matched the study inclusion were identified. Glandular abnormalitywas detected by Pap smears in 22 women (43.1%). Among 29 women with squamous lesions on Pap smears, 9additional glandular abnormalities were detected on CDB and/or ECC. In total, glandular abnormality was suspectedin 31 women (60.8%) preoperatively. According to the histological type of AIS, glandular abnormality suspectedfrom preoperative evaluation was noted in 20 women (70.4%) who had pure AIS. Among women with mixed AIS/HSIL, only 12 women (50.0%) had preoperative evaluation suggesting glandular abnormality. These data demonstratethat the sensitivity of combining Pap smear, CDB and/or ECC in detecting glandular lesions before conizationcontaining AIS appears to be suboptimal. Further study concerning the improvement of detecting AIS before conizationis warranted to select the most appropriate diagnostic conization method for such lesions.     

Clinical significance of atypical glandular cells of undetermined significance in postmenopausal women

BACKGROUND: Glandular atypia in Papanicolaou (Pap) smears from postmenopausal women is encountered frequently. This finding can be the result of artifactual alterations such as drying artifacts and inflammatory changes or may represent a squamous or glandular, preneoplastic or neoplastic process. Therefore, it is important to determine the clinical implication of a diagnosis of atypical glandular cells of undetermined significance (AGUS) in postmenopausal patients. METHODS: A total of 30,036 Pap smears were obtained from postmenopausal women between 1995 and 1997. Among these smears, 154 (0.51%) had a diagnosis of AGUS. Follow-up was available for 133 patients (86.4%); 110 patients (82.7%) had histologic follow-up (including cervical biopsy, endocervical [EC] curettage, and/or endometrial [EM] biopsy) and 23 patients (17.3%) had repeat smears. RESULTS: Thirty-six of 110 patients (32.7%) were found to have a clinically significant lesion (defined as a preneoplastic or neoplastic, glandular or squamous lesion) on subsequent histologic follow-up. Nineteen patients (53%) had glandular lesions (15 EM adenocarcinoma [ACA] cases, 2 EC ACA cases, 1 EC adenocarcinoma is situ case, and 1 EM hyperplasia case). Seventeen patients (47%) had a squamous intraepithelial lesion (SIL) (6 cases of low-grade SIL, 9 cases of high-grade [HGIL], and 2 cases of squamous cell carcinoma). Among those patients with repeat Pap smears, five patients had persistent AGUS/atypical squamous cells of undetermined significance and one patient had an SIL. CONCLUSIONS: The incidence of AGUS among postmenopausal patients was similar to that of the general population (0.51% vs. 0.56%; P > 0.05). A significant percentage of these patients were found to have a clinically significant lesion on subsequent follow-up. Furthermore, a majority of these lesions were ACA (53%) or HGSIL (26%). The findings of the current study strongly suggest the need for the close follow-up of postmenopausal patients with a diagnosis of AGUS. Cancer (Cancer Cytopathol) Copyright 2001 American Cancer Society.     

Liquid-based cytology versus conventional Papanicolaou smear in an organized screening program : a prospective randomized study

BACKGROUND: The objective of this study was to evaluate whether liquid-based cytology (LBC) can improve high-standard cervical cancer screening cytology further. The primary endpoint was histopathologic high-grade lesions in current and subsequent screening rounds. The secondary endpoints were cytologic diagnosis and inadequate samples. METHODS: Women were randomized to smear taking by conventional Papanicolaou (Pap) smear or LBC according to the time of appointment. Eight thousand eight hundred ten conventional Pap smears and 4674 LBC samples were included. Evaluations of atypical cytology and referral to colposcopy and treatment were performed as routine procedures. Histopathologic diagnoses were retrieved from a regional database 8 months after the study was closed. The mean follow-up was 2 years and 9 months. RESULTS: Inadequate samples were observed in 0.3% of LBC samples versus 0.7% of Pap smears (P = .002). The total fraction of nonbenign diagnoses in cytology was 4.5% versus 3.5%, respectively (P < .001). Histopathologic evaluation was made on 570 patients constituting 4.6% of the LBC samples and 4% of the Pap smears. Forty percent more high-grade lesions were identified as a result of LBC sampling (1.20% vs 0.85%; P = .05). The influence of the sampling method was significant for all variables (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.12-2.28) for high-grade lesions that were identified by histology when adjusting for age and screening unit in a logistic regression model. At the second follow-up 2 years and 1 month later, the OR was decreased only slightly (1.51; 95% CI, 1.13-2.01). CONCLUSIONS: In the ongoing cervical screening program of western Sweden, liquid cytology produced a significantly higher yield of histologic high-grade lesions compared with conventional Pap smears.     

Severe cervical glandular cell lesions and severe cervical combined lesions: predictive value of the papanicolaou smear

BACKGROUND: The purpose of the current study was to determine the accuracy of routinely screened cervical smears to predict a glandular cell lesion in histologically confirmed cases of cervical adenocarcinoma in situ (AIS), invasive adenocarcinoma (ADCA), adenosquamous carcinoma (ADSQCA), and severe combined glandular and squamous cell lesions. METHODS: Between 1989-2000, a total of 1,141 women with a histologic diagnosis of cervical AIS, ADCA, ADSQCA, and combined lesions (glandular cell lesion with a coexistent squamous cell lesion) were registered in the Dutch National Pathology Archive (PALGA). In 1054 of these 1,141 histologic cases, an additional conventional Papanicolaou (Pap) smear diagnosis was registered from the same patient. Material was evaluated with regard to the accuracy of cytologic diagnosis, the percentage of combined lesions, the mean age of the patients, and the time interval between AIS and ADCA. RESULTS: Of 1,141 registered histologic cases, 57.5% were registered as having an "intraepithelial" lesion, whereas 42.5% were registered as having an "invasive" process. A combined process was diagnosed in 63.2% of cases. From the same patients, a cytologic diagnosis of a severe cervical epithelial lesion was registered in PALGA for 91.2% (n = 961) of 1054 cases. A cytologic registration of a severe glandular cell lesion (with or without a squamous cell component) was made in 547 cases (51.9%). Prediction of a severe glandular cell lesion on the Pap smear was found to be more accurate in cases of histologically confirmed pure glandular cell abnormalities than in cases with a histologic diagnosis of a combined lesion. The cytologic prediction was found to be correct in 75.2% of cases of pure AIS and 47.3% of cases of AIS with coexistent high-grade squamous intraepithelial lesion (HGSIL) (cervical intraepithelial lesion [CIN] type 2 [CIN 2] or CIN 3). The mean ages of the patients with AIS and AIS + HGSIL were 37.3 years and 34 years, respectively, whereas the mean age of the patients with ADCA and ADCA + HGSIL was 41.9 years and 38.1 years, respectively. The interval between the average ages of patients with AIS and ADCA and those with AIS + HGSIL and ADCA + HGSIL was 4.6 years and 4.1 years, respectively. CONCLUSIONS: On the basis of a data search of the PALGA registry, it can be concluded that in a relatively large number of cases a severe cervical glandular cell lesion was not diagnosed on the Pap smear. Furthermore, data demonstrated that the prediction of a glandular abnormality is less accurate in cases of combined squamoglandular cell lesions than in pure glandular cell lesions.     

Liquid-based cytology for primary cervical cancer screening: a multi-centre study

The aim of this six-centre, split-sample study was to compare ThinPrep fluid-based cytology to the conventional Papanicolaou smear. Six cytopathology laboratories and 35 gynaecologists participated. 5428 patients met the inclusion criteria (age > 18 years old, intact cervix, informed consent). Each cervical sample was used first to prepare a conventional Pap smear, then the sampling device was rinsed into a PreservCyt vial, and a ThinPrep slide was made. Screening of slide pairs was blinded (n = 5428). All non-negative concordant cases (n = 101), all non-concordant cases (n = 206), and a 5% random sample of concordant negative cases (n = 272) underwent review by one independent pathologist then by the panel of 6 investigators. Initial (blinded) screening results for ThinPrep and conventional smears were correlated. Initial diagnoses were correlated with consensus cytological diagnoses. Differences in disease detection were evaluated using McNemar's test. On initial screening, 29% more ASCUS cases and 39% more low-grade squamous intraepithelial lesions (LSIL) and more severe lesions (LSIL+) were detected on the ThinPrep slides than on the conventional smears (P = 0.001), including 50% more LSIL and 18% more high-grade SIL (HSIL). The ASCUS:SIL ratio was lower for the ThinPrep method (115:132 = 0.87:1) than for the conventional smear method (89:94 = 0.95:1). The same trend was observed for the ASCUS/AGUS:LSIL ratio. Independent and consensus review confirmed 145 LSIL+ diagnoses; of these, 18% more had been detected initially on the ThinPrep slides than on the conventional smears (P = 0.041). The ThinPrep Pap Test is more accurate than the conventional Pap test and has the potential to optimize the effectiveness of primary cervical cancer screening.     

Identification of progressive cervical epithelial cell abnormalities using DNA image cytometry

BACKGROUND: The objectives of the current study were to compare the capabilities of conventional cervical cytology and of DNA image cytometry (DNA-ICM) in the prediction of progressive or regressive behavior in atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL), and atypical glandular cells (AGC). METHODS: One hundred ninety-six women with Papanicolaou (Pap) smears that yielded diagnoses of ASC, LSIL, or AGC were included in a prospective cohort study. Slides were classified according to the Bethesda system. DNA-ICM was performed according to the consensus reports of the European Society of Analytical Cellular Pathology. RESULTS: Reference standard verification was available in 108 patients. The rate of DNA aneuploidy in Pap smears increased significantly from cervical intraepithelial neoplasia 1 (CIN1) (54%) and CIN2 (64.3%) to CIN3 or greater (CIN3+) (83.3%) in subsequent biopsies (P < 0.05). Using ASC, LSIL, and AGC as input cytologic diagnoses and >/= CIN2 as the output histologic diagnosis, the positive predictive values (PPVs) for conventional cytology and DNA-ICM were 35.2% and 65.9%, respectively (P < 0.001). The negative predictive value (NPV) of DNA-ICM was 85.0%. When >/= CIN3 was used as the output histologic diagnosis, conventional cytology had a PPV of 22.2%. The PPV and NPV of DNA-ICM were 43.9% and 93.3%, respectively. CONCLUSIONS: The results of the current study confirmed the prognostic validity of DNA image cytometry for differentiation between progressive and regressive lesions in patients with ASC, LSIL, and AGC diagnoses.     

Assessment of reflex human papillomavirus DNA testing in patients with atypical endocervical cells on cervical cytology

BACKGROUND: Reflex human papillomavirus (HPV) testing for atypical squamous cells of undetermined significance (ASC-US) has improved the sensitivity and specificity in detecting high-grade squamous dysplasia (cervical intraepithelial neoplasia [CIN]2+). However, to the authors' knowledge there are no guidelines for performing reflex HPV testing in women with atypical endocervical cells (AEC) before colposcopy. This report is of a 5-year experience with reflex HPV testing in women with AEC and assessment of the potential role of reflex HPV testing in guiding subsequent colposcopy-directed cervical biopsy/curettage in a large tertiary care hospital setting. METHODS: All AEC cases cytologically diagnosed from July 2001 to June 2006 were retrieved from the Cleveland Clinic database. The histopathologic diagnoses and the results of HPV testing using the Hybrid Capture 2 (HC-II) method were reviewed. The most severe histopathologic diagnosis was recorded. RESULTS: Of a total 332,470 Papanicolaou (Pap) tests performed, 317 cases of AEC had histopathologic follow-up and reflex testing for high-risk HPV. Histopathologic examination of the 64 HPV-positive AEC cases revealed 18 cases of endocervical adenocarcinoma in situ/adenocarcinoma (AIS+) and 22 cases of CIN2+. Among 253 of the HPV-negative AEC women, AIS+ was found in only 3 cases and CIN2+ in 1 case. Cervical AIS+ was found in 28% of the HPV-positive AEC patients and in only 0.9% of the HPV-negative patients (P<.0001). When the significant glandular (AIS+) and squamous (CIN2+) lesions were combined, 62.5% of the lesions were detected in HPV-positive AEC cases compared with 1.6% in the HPV-negative AEC cases (P<.0001). CONCLUSIONS: Because of a high sensitivity (91.0%) and high specificity (91.2%) in detecting significant cervical lesions, reflex HPV testing for cytologic diagnosis of AEC appears to be a useful ancillary tool in the selection of high-risk patients for colposcopy.     

Cytohistologic correlation rates between conventional Papanicolaou smears and ThinPrep cervical cytology: a comparison

BACKGROUND: The ThinPrep Papanicolaou (Pap) test, a liquid-based alternative to the long-used conventional Pap smear, received Food and Drug Administration approval in 1996. The current study is a comparison of the accuracy, as assessed by cytohistologic correlation, of conventional versus ThinPrep Pap smears in a hospital setting. METHODS: A retrospective analysis of all patients who underwent Pap smears (conventional and ThinPrep) and pertinent surgical pathology tissue processed in our department over a 1-year period was undertaken. Tissue diagnoses were grouped into broad general categories to correlate with the Bethesda system. The statistical significance of differences between the two types of Pap test results compared with tissue diagnoses was assessed using a chi-square test with 1 degree of freedom and an alpha value of 0.05. RESULTS: Of the 65,421 Pap smears interpreted during the study period, histologic correlation was possible in 1544 patients. Of those diagnosed as negative (644 conventional and 245 ThinPrep Smears), low-grade squamous intraepithelial lesion (LGSIL) (116 conventional and 114 ThinPrep smears), and high-grade squamous intraepithelial lesions (HGSIL) (142 conventional and 131 ThinPrep smears), there was no statistically significant difference found between the correlation rates of conventional and ThinPrep Pap smear results. However, review of all cases of invasive cervical carcinoma identified during this time period showed the ThinPrep to be less consistent in predicting the presence of invasive carcinoma compared with the conventional Pap smear. CONCLUSIONS: Based on cytohistologic correlation evidence, the ThinPrep Pap test may not be more effective in detecting cervical disease, particularly invasive carcinoma, when compared with the conventional Pap smear.     

The Bethesda system and evaluation of abnormal pap smears

The Bethesda Pap Smear system and its 1991 revisions aim to simplify Papanicolaou (Pap) smear reporting and make it more reproducible. It redefines the Pap smear request as a medical consultation. The pathologist consultant is required not only to provide the smear reading but also its clinical recommendation. The Bethesda system insists on a detailed Pap smear report assessing specimen adequacy and types of epithelial changes. Squamous cell abnormalities are grouped according to their biologic potential. Both cervical intraepithelial neoplasia, grade I (CIN I) (mild dysplasia) and human papillomavirus (HPV) lesions are grouped together as low-grade squamous intraepithelial lesions (LGSIL), while moderate and severe dysplasia (CIN II and III) belong to the high-grade squamous intraepithelial lesion (HGSIL) category. Atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGCUS) need further qualification as to whether they favor either a reactive or neoplastic process. Guidelines for management of abnormal Pap smears are discussed in detail.     

"See and treat" approach is appropriate in women with high-grade lesions on either cervical cytology or colposcopy

This study was undertaken to evaluate the overtreatment rate of women with abnormal cervical cytology undergoing colposcopy followed by loop electrosurgical excision procedure (LEEP), the so-called "see and treat" approach. Overtreatment was defined as LEEP specimens containing cervical intraepithelial neoplasia (CIN) 1 or less. In this study, medical records of 192 women with abnormal Pap smears undergoing the "see and treat" approach in Chiang Mai University Hospital between October 2008 and October 2010 were reviewed. The preceding Pap smears were as follows: 124 (64.6%) with high-grade squamous intraepithelial lesion (HSIL); 35 (18.2%) with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H); 20 (10.4%) with low-grade squamous intraepithelial lesion (LSIL); 9 (4.7%) with squamous cell carcinoma (SCCA); and 4 (2.1%) with atypical squamous cells of undetermined significance (ASC-US). Histologic results obtained from loop electrosurgical excision procedure (LEEP) were as follows: CIN 2-3, 106 (55.2%); invasive cancer, 41 (21.4%); CIN 1, 15 (7.8%); adenocarcinoma in situ (AIS), 1 (0.5%); and no lesion, 29 (15.1%). Overall, 22.9% of LEEP specimens contained CIN 1 or less. Significant predictors for overtreatment were type of preceding smears and colposcopic impression. If the "see and treat" approach was strictly carried out in women who had either smears or colposcopic findings revealing high-grade disease, the overtreatment rate was only 7%. Hemorrhagic complication was 6.2% and all could be treated at an outpatient department. In conclusion, the overtreatment rate of the "see and treat" approach in women with various degree of abnormal Pap smears is 23% which would be diminished to the acceptable rate of lower that 10% if strictly performed in those with either smears or colposcopic impressions revealing high-grade abnormality. Peri-operative LEEP complications were mild and acceptable.     

Glandular cell atypia on Papanicolaou smears: interobserver variability in the diagnosis and prediction of cell of origin

BACKGROUND: The 2001 Bethesda System recommended qualification of atypical glandular cells (AGC) to indicate the site of origin and separated endocervical adenocarcinoma in situ (AIS) from "AGC favor neoplastic" as a specific diagnostic category. To the authors' knowledge, the literature evaluating the reproducibility of Papanicolaou (Pap) smear diagnosis of glandular cell abnormalities with emphasis on the cell of origin is limited. The aim of the current study was to investigate whether a variety of benign to neoplastic glandular lesions can be reliably classified on Pap smear with regard to diagnosis and cell of origin. METHODS: Twenty-three conventional Pap smears (CPS) with glandular cellular changes varying from benign to adenocarcinoma (ACA) were reviewed by six observers. They were asked to categorize each smear according to cell of origin (endocervical vs. endometrial) and diagnosis (benign, AGC, or ACA). Kappa statistics were used to evaluate interobserver agreement and correlation of interobserver agreement with experience. RESULTS: There was no consensus among observers for both the origin of the cells and the diagnosis. Interobserver agreement for site was poor (kappa < 0.4) especially in the AGC category. Unanimous agreement for site was reached for 7 of 23 smears (30%). Two of five endocervical AIS were classified as endometrial and another two were classified as benign by four observers. Interobserver agreement was poor in all diagnostic categories (kappa < 0.4) and showed slight correlation with level of experience. Unanimous agreement for diagnosis was reached for only 2 smears (9%). Three of 11 (27%) smears demonstrating preneoplastic/neoplastic processes were diagnosed as benign by 3 observers. Three (25%) benign CPS were diagnosed as ACA by 2 observers. Accurate prediction of the final histologic diagnosis by observers varied from 30% to 87% and did not correlate closely with experience. CONCLUSIONS: Cytologic diagnosis of glandular lesions by CPS was problematic and suffered from significant interobserver subjectivity.     

Liquid‐based cytology versus conventional Papanicolaou smear in an organized screening program

BACKGROUND.

The objective of this study was to evaluate whether liquid‐based cytology (LBC) can improve high‐standard cervical cancer screening cytology further. The primary endpoint was histopathologic high‐grade lesions in current and subsequent screening rounds. The secondary endpoints were cytologic diagnosis and inadequate samples.

METHODS.

Women were randomized to smear taking by conventional Papanicolaou (Pap) smear or LBC according to the time of appointment. Eight thousand eight hundred ten conventional Pap smears and 4674 LBC samples were included. Evaluations of atypical cytology and referral to colposcopy and treatment were performed as routine procedures. Histopathologic diagnoses were retrieved from a regional database 8 months after the study was closed. The mean follow‐up was 2 years and 9 months.

RESULTS.

Inadequate samples were observed in 0.3% of LBC samples versus 0.7% of Pap smears (P = .002). The total fraction of nonbenign diagnoses in cytology was 4.5% versus 3.5%, respectively (P < .001). Histopathologic evaluation was made on 570 patients constituting 4.6% of the LBC samples and 4% of the Pap smears. Forty percent more high‐grade lesions were identified as a result of LBC sampling (1.20% vs 0.85%; P = .05). The influence of the sampling method was significant for all variables (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.12–2.28) for high‐grade lesions that were identified by histology when adjusting for age and screening unit in a logistic regression model. At the second follow‐up 2 years and 1 month later, the OR was decreased only slightly (1.51; 95% CI, 1.13–2.01).

CONCLUSIONS.

In the ongoing cervical screening program of western Sweden, liquid cytology produced a significantly higher yield of histologic high‐grade lesions compared with conventional Pap smears. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

Value of colposcopy in the early diagnosis of cervical cancer in patients with abnormal pap smears at Shahid Sadoughi hospital, Yazd

Background and objectives: Cervical cancer is preventable, although it is common in developing countries and Iran, where there is no defined approach to “atypical squamous cells of undetermined significance” (ASCUS) on Pap smears. This study determined the value of colposcopy in the early diagnosis of cervix cancer in females with ASCUS. Materials and methods: This accuracy study examined 213 ASCUS cases referred from different cities from 2007 to 2009. All patients underwent a repeated conventional Pap smear, colposcopy, endocervical curettage, and a cervical biopsy, considered the gold-standard diagnostic test. Results: There was no significant relationship between age, age of first intercourse, smoking, or number of children and a positive cervical biopsy. The sensitivity and specificity of a repeat Pap smear for ASCUS were 15 and 93%, respectively, while the respective values for diagnosing cervical cancer with colposcopy were 80 and 80%. Endocervical curettage had 64% sensitivity and 100% specificity for diagnosing cervical cancer, and 11 positive neoplastic or malignant lesions reported on endocervical curettage were confirmed by biopsy. Discussion: Based on the low accuracy of the Pap smear in Iran as a developing country and the need for an early diagnosis of cervical cancer, a cervical biopsy and colposcopy are recommended for these patients. Colposcopy and endocervical curettage alone are better diagnostic tools than a repeat Pap smear for unsatisfactory Pap smears.     

Clinical evaluation of atypical glandular cells of undetermined significance upon cervical cytologic examination in Israeli Jewish women

The adjusted incidence of cervical carcinoma among Israeli Jewish women is approximately 5 out of 100 000. This retrospective study sought to determine the clinical implications of finding atypical glandular cells of undetermined significance (AGUS) in cervical cytologic specimens in this population. Cervical cytologic examinations during January 2001-June 2003 diagnosed as AGUS were identified by a computerised database. Medical records were reviewed to determine the presence or absence of associated significant pathologic conditions of the cervix and identified 45 out of 11 800 patients (0.38%) with AGUS. AGUS was the only cytologic diagnosis in 14 patients, while 31 patients had both AGUS and an additional atypical squamous cell of undetermined significance (ASCUS). All subjects underwent colposcopy, endocervical curettage, and cervical biopsy. A clinically significant diagnosis (cervical intraepithelial neoplasia (CIN) II, CIN III, or carcinoma) was made in 24 patients (53.3%), including cancer in three (6.7%): one had microinvasive adenocarcinoma and two had microinvasive squamous cell carcinoma. Squamous carcinoma coexisting with a clinically significant lesion carried a risk of 61.3%, compared with a risk of 35.7% for AGUS alone (P=0.20). Detection of AGUS during cervical cytologic screening, especially with a coexisting ASCUS, indicates the existence of serious pathologic processes; management by cervical colposcopy, endocervical curettage, and cervical biopsy is recommended.