Intraobserver and interobserver variability in the diagnosis of epithelial abnormalities in cervical smears

In a study of variability in the diagnosis of epithelial abnormalities, cervical smears with abnormalities of different severity were rescreened twice by 19 observers with an interval of six months. The observers focused on grading atypicality of squamous, squamous metaplastic and endocervical columnar epithelial cells; their results were compared (1) for the two screenings to assess intraobserver variability and (2) to "review" (final) diagnoses to assess interobserver variability. When the same observer rescreened a smear, 83.3% of the diagnoses did not differ more than one grade between two screenings; however, average intraobserver variability differed considerably for individual observers. The intraobserver variability was only slightly (not significantly) influenced by the years of experience in cytopathology of the observers. Intraobserver variability proved to be an important factor in incorrect diagnoses: 49.1% of the smears with false-negative and 52.9% with false-positive diagnoses at the first rescreening were correctly assessed at the second rescreening. Of all diagnoses made at rescreening, 80.9% were in agreement with the review diagnosis. The interobserver variability also showed considerable differences between observers; however, there was a strong influence of the experience of the observer on the interobserver variability. Atypicality grading of endocervical columnar epithelium by the observers showed a low correlation with the review diagnoses. The relatively low accuracy in the evaluation of this kind of epithelial abnormality is likely to be attributable to the low incidence of abnormal changes of endocervical columnar epithelium. The results of this study point to intraobserver variability as the main cause of false diagnoses. When wrongly diagnosed, severe epithelial abnormalities are more often underestimated than completely overlooked. Apart from training in cytopathology, the establishment of laboratory protocols for multiple screening of even minor abnormalities seem to be the most effective means of reducing the number of false diagnoses.     

Immunocytochemical staining of cervical smears for the diagnosis of cervical intraepithelial neoplasia

A total of 233 cervical smears were stained by immunocytochemical methods for epithelial membrane antigen (EMA); the findings were compared with those from Papanicolaou-stained smears from the same women. Squamous epithelial cells from normal cervices did not stain, but cells shed from cervices with cervical intraepithelial neoplasia (CIN) did express the EMA marker. Metaplastic cells from normal and abnormal cervices also frequently stained. The results confirm that this marker detects cervical intraepithelial neoplasia in vitro, but its potential use in an automated screening program may be limited by the staining of the metaplastic cells.     

The influence of sample takers on the cellular composition of cervical smears

In a population-based cervical cancer screening program, the performances of five sample takers and their influence on the cellular composition of the smears and the numbers of epithelial abnormalities diagnosed were analyzed. As measured by the presence of endocervical columnar cells, there were remarkable variations in the quality of the smears between sample takers and between years of sampling. There was also a positive relationship between the presence of endocervical columnar cells in the smear and the number of epithelial abnormalities found. A lower quality of smear was reflected by a lower incidence of epithelial atypical changes found, both between sample takers and by a single sample taker over a period of time. These findings show that sample takers influence the cellular composition of smears and, therefore, the diagnostic outcome of smear screening. Their competence in executing their tasks must be frequently reviewed.     

Analysis of cervical smears obtained within three years of the diagnosis of invasive cervical cancer

The cytologic histories of 376 women presenting with invasive carcinoma of the cervix were analyzed. In total, 202 (53.7%) of these women had had 355 smears taken during the three years preceding presentation. All 320 smears with an original cytologic diagnosis of less than cancer were reviewed. The original cytologic diagnosis was low in 95 (30.6%) of 310 adequate smears. Originally, 96 (30.9%) of the adequate smears were evaluated as negative; at review, only 55 (17.5%) of the adequate smears were evaluated as negative. Comparing the review diagnoses to the 355 total smears, the rates of negative smears were 13.5% (42 of 310) for squamous-cell carcinoma, 30.0% (12 of 40) for adenocarcinoma and 20.0% (1 of 5) for adenosquamous carcinoma (P less than .05). The cellular composition of the smear was significantly related to the cytologic detection of abnormalities: endocervical cylindrical and/or metaplastic cells were seen in only 45.5% of smears diagnosed as negative, but in 84.4% and 97.8% of smears diagnosed as atypia and cervical intraepithelial neoplasia, respectively P less than .00001). Smears without endocervical cells should be considered inadequate and should be repeated.     

Fluorescent studies directed towards the location of abnormal epithelial cells in cervical smears

Cervical screening is concerned with the search for abnormal epithelial cells in smears prepared from scrapings from the uterine cervix. It is a highly skilled labour intensive operation and automated methods of detecting dyskariotic cells in cervical smears would be helpful. We report a fluorescence method of detecting abnormal cervical cells in smears and biopsies using a probe for guanidinobenzoatase. This approach has the potential for automation.     

Relationship between the cellular composition of sputum and the cytologic diagnosis of lung cancer

In 410 patients with either a primary or a metastatic malignant lung process, the cellular composition of the sputum specimens was analyzed in relation to the diagnostic accuracy of sputum cytology and in relation to anamnestic and clinical patient characteristics. In patients with primary lung cancer, sputum samples with true-positive cytologic diagnoses contained significantly more cells from the deeper airways, such as alveolar macrophages and bronchial columnar cells, than did sputum specimens with a false-negative diagnosis, even though these cell types were present in both types of specimens. In sputum samples from patients with metastatic lung malignancies, differences in cellular composition of specimens with true-positive and false-negative diagnoses were not significant.     

Microglandular hyperplasia of the uterine cervix. Cytologic diagnosis in cervical smears

OBJECTIVE: To identify cytomorphologic features specific to microglandular hyperplasia (MGH) in cervical cytologic smears. STUDY DESIGN: Twenty-four cervical smears from 24 patients obtained before the histologic diagnosis of MGH made on colposcopically directed biopsies during a period of two years (1995-1997) were evaluated. RESULTS: Of cases with MGH, 13/24 (54%) showed the presence of bidimensional or tridimensional cellular clusters made up of cubic or cylindrical glandular cells with vacuolated cytoplasm; cells with dense cytoplasm, basaloid in appearance, corresponding to immature squamous metaplasia; and subcylindrical reserve cells with small, round nuclei and scant cytoplasm. Clusters showed microlumina or fenestrated spaces, preserved polarity and absence of nuclear peripheral dispersion. In the control group these cellular clusters were found in 6/100 (6%). Statistical analysis (chi 2) showed a strong, highly significant association (P < 0.001) of the cytologic parameters selected and the histologic diagnosis of MGH. CONCLUSION: Until now, no specific cytologic parameters were described for MGH. This study underscored the value of cytomorphologic parameters described for typical cellular clusters showing microlumina or fenestrated spaces with shared party walls and an admixture of glandular cells, and immature squamous metaplastic and subcylindrical reserve cells in the cytologic diagnosis of MGH.     

Ethnic patterns of cytologic abnormalities in cervical smears in suriname, a high-risk area for cervical cancer

OBJECTIVE: To determine the prevalence of cytologic abnormalities in cervical smears from women attending the first organized screening program in Suriname and to compare the prevalences in 4 Surinamese ethnicities with different cervical carcinoma incidences. STUDY DESIGN: Cervical scrapes were taken from women with 4 different ethnicities: Maroons, Amerindians, Javanese and Hindustani. Papanicolaou staining and cytologic screening were performed on 807 cervical smears. RESULTS Cervical cytologic abnormalities were seen in 13.4%, of which 8.1% (62 of 764) had atypical changes, 2.6% (20 of 764) had mild and 2.6% (20 of 764) had moderate and severe dysplasia/carcinoma in situ (CIS). The cytologic abnormalities varied between the ethnicities: 42.1% (83 of 197) in the Maroons and 2.3% (4 of 176), 5.0% (9 of 183) and 3.0% (6 of 208) in the Javanese, Amerindians, and Hindustani, respectively. CONCLUSION: The high prevalence of moderate and severe dysplasia/CIS in all ethnicities correlates with the high cervical carcinoma incidence in Suriname. A significantly higher prevalence of mild abnormalities in the Maroons was observed; it did not reflect the relatively low cervical cancer incidence in this ethnicity. However, this can be explained by the possibility that these women have a different sexual lifestyle, leading to a higher prevalence of     

Effect of circulation and discussion of cervical smears on agreement between laboratories

The study objective was assessing whether circulation of smears and discussion of those with differing interpretation can increase reproducibility between laboratories. The study included: the blind interpretation of a first set of 194 smears among seven laboratories, the discussion of smears with discrepant diagnoses during the previous phase and the blind interpretation of a second set of smears of same size and characteristics. After discussions, the overall weighted kappa increased in five laboratories (substantially in three : +50%, +27% and +20%). However, no change was observed in one laboratory and a slight decrease (-4%) in another. The latter interpreted the second set of smears at a longer time interval from discussions. Agreement improved for all diagnostic classes except low grade intraepithelial neoplasia (LSIL). Overall, the intervention increased diagnostic agreement, but its effect varied with laboratory and by diagnostic class and could be transient. Continued programmes of smear exchange and discussion appear to be advisable.     

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

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

Classification of cervical smears with discordance between the cytologic and/or histologic ratings

The problems of diagnostic variability between certified cytotechnologists was studied. Three cytology laboratories submitted a total of 28 cervical smears that had a discordance between the cytologic and/or histologic ratings. Eight independent cytotechnologists provided blind readings on each slide, expressed as "absence of cervical intraepithelial neoplasia (CIN)" to "CIN III." The median rating was absence of CIN or CIN I for 8 slides, CIN II for 5 and CIN III for 15. With a kappa value greater than 0 reflecting agreement beyond chance expectation and a value of 0.40 indicating fair agreement, the kappa value for 8 X 28 ratings was 0.36 (P = .0001), with a 90% confidence interval (CI) between 0.34 and 0.37. The kappa value was 0.14 (P = .10), with a 90% CI between 0.10 and 0.18, on a subsample of nine smears with two or more positive cytology diagnoses but a negative histology. Sixteen of the 28 slides represented cases of histologically proven cancer. Treating cytologic diagnoses of CIN II and CIN III as positive, the sensitivity of the cytologist with reference to histology varied between 71% and 86% while the specificity ranged from 18% to 62%. The positive predictive value was 1/2.5 to 1/1 and the negative predictive value was 1/6 to 1/1. The predictive power (true positives/false positives) ranged from 1.0 to 2.2. The cytodiagnosis of these cervical smears from cases of discordance thus exhibited limited reliability. Standardization of the relevant cytologic knowledge and its routine application is needed to improve the level of performance.     

Cellular composition of cervical smears in relation to the day of the menstrual cycle and the method of contraception

The influence of the day of the menstrual cycle and the method of contraception on the cellular composition of cervical smears was investigated. The percentage of unsatisfactory smears during the first four days of the cycle was understandably very high, leaving only 80% of the smears of sufficient quality for cytologic diagnosis. The percentage of smears of insufficient quality during the remainder of the cycle was significantly higher in women using oral hormonal contraceptives. The percentages of smears containing endocervical columnar cells, a criterion for judging smears to be of high quality, differed significantly among women using different modes of contraception. The highest percentage of smears without endocervical columnar cells was found in women using oral contraceptives; during the first half of the cycle in these women, smears were of higher quality than during the second half of the cycle. In women not practicing contraception or using nonhormonal methods of contraception, the differences in cellular composition during the cycle, though significant, were too small to be of practical importance. Women using oral contraceptives thus have an increased risk for a potential false-negative diagnosis because of the higher percentage of smears of unreliable quality taken in these women. In women using oral hormonal contraceptives, smears should be taken during the first half of the cycle because of the higher percentage of smears of high quality in that period.     

The significance of endocervical cells in the diagnosis of cervical epithelial changes

A study was made of the relationship of endocervical columnar cells to the cytologic identification of abnormality in the cervix. From a population of women participating in a cervical cancer screening program, a group of women was selected whose smears theoretically should have contained endocervical columnar cells. Endocervical cells were present in 93.1% of the smears and absent in 6.9%. A significantly higher number of moderately and severely atypical epithelial changes was found in smears with endocervical cells as compared with smears without endocervical cells.