Consequences of the introduction of combined spatula and Cytobrush sampling for cervical cytology. Improvements in smear quality and detection rates

One of the most important yardsticks for evaluating sampling for the detection of premalignant and malignant cervical lesions is the percentage of smears that contain cells from the transformation zone. Until February 1985, all smears made by around 500 different general practitioners were taken with a modified Ayre spatula. In the period February to October 1985, 24,496 smears of spatula samples and 5,716 smears prepared by combined spatula-Cytobrush sampling were analyzed. With the introduction of the combined spatula-Cytobrush method, the rate of smears containing cells from the transformation zone (adequate smears) rose from 84% to 98%. With the spatula-alone method, there were large differences between the rates of adequate smears from the various doctors; with the combined spatula-Cytobrush method, all participating doctors were without exception highly successful. The positive cytology rate was significantly higher in the combined spatula-Cytobrush smears (0.75%) as compared with the spatula-alone smears (0.38%). There was also a change in the diagnostic pattern in that more premalignant changes of the glandular epithelium of the endocervix were detected. One case of early invasive adenocarcinoma of the endocervix, in which the combined spatula-Cytobrush smears was positive and the repeat spatula-alone smear made by the gynecologist was negative, is discussed in detail. We anticipate that, with the large-scale introduction of the Cytobrush sampling method, fewer repeat smears will be required and, in addition, the observed relative increase of endocervical adenocarcinoma of the endocervix will be halted. In addition, there will be fewer false-negative smears.     

Comparison of spatula and nonspatula methods for cervical sampling

A comparison between nonspatula (cotton swab and Cytobrush) cervical sampling methods and spatula (wooden Ayre spatula and plastic extended-tip Szalay Cyto-Spatula) sampling methods was made in 109 cases. Based on the presence of endocervical cells, there were statistically significant qualitative differences between the non-spatula methods as well as between the spatula methods, but not between the Cytobrush and Cyto-Spatula smears or the cotton swab and Ayre spatula smears. In all kinds of inflammatory lesions, the spatula samples were more accurate and diagnostic than the nonspatula ones. In all cases of cervical intraepithelial neoplasia and in most cases of squamous metaplasia, the Cyto-Spatula sample was the most accurate. It is concluded that the Szalay Cyto-Spatula method is superior to the other cervical sampling methods because it provides well-preserved cells from both the endocervix and the ectocervix in one smear. The Cytobrush should be used in conjunction with spatula sampling (combination method) for effective sampling of the cervix. The Cytobrush alone is effective mainly for endocervical sampling while the Ayre spatula alone is effective mainly for ectocervical sampling; the cotton swab is ineffective for both endocervical and ectocervical sampling.     

Comparison of Cytobrush sampling, spatula sampling and combined Cytobrush-spatula sampling of the uterine cervix

Since the introduction of the Cytobrush for sampling the uterine cervix, some practitioners have ceased taking a concomitant cervical scraping using a spatula. To examine whether Cytobrush sampling alone is adequate for the diagnosis of cervical lesions, the Cytobrush and spatula samples in 444 smears (most with original diagnoses of at least mild dysplasia) were analyzed separately for the presence of diagnostic cells, endocervical cells and squamous cells. Of the 412 smears showing pathologic findings (mild to severe dysplasia or worse), diagnostic cells were present in 400 Cytobrush samples and in 369 spatula samples; the combination of both samples thus gave a 3% gain in correct diagnoses as compared to use of the Cytobrush samples alone. Another 18 smears would have been underdiagnosed based only on the Cytobrush samples. Endocervical cells were present in 95.3% of the Cytobrush samples and 83.8% of the spatula samples; squamous cells were present in 93.9% of the Cytobrush samples and 96.8% of the spatula samples. Analysis confirmed that it is important that the smear should contain both endocervical and squamous cells. A positive relationship between the absence of squamous cells in the Cytobrush sample and the probability of a false-negative assessment was suggested. It thus seems inadvisable to replace the combination sampling method by Cytobrush sampling alone, which may lead to a false-negative diagnosis.     

Cervical smears following laser treatment. Comparison of Cervex brush versus Cytobrush-Ayre spatula sampling

For 802 women at initial follow-up after laser treatment of cervical lesions, 421 smears prepared using the Cervex brush were compared with 381 smears prepared using the combination of a Cytobrush plus an Ayre spatula. The smears were graded for adequacy, the presence of endocervical or metaplastic cells and the presence and degree of epithelial abnormalities. Endocervical or metaplastic cells were seen more often in Cytobrush-Ayre spatula smears (94.5%) as compared with Cervex brush smears (88.8%; P = .004). Also, the number of samples classed as inadequate was significantly greater with Cervex brush smears (4.0%) than with Cytobrush-Ayre spatula smears (0.3%; P = .0003). The number of smears showing dysplasia was too small to detect realistic differences between the two sampling methods. These findings suggest that, in women who have had laser treatment of the cervix, Cytobrush plus Ayre spatula sampling produces better-quality smears than does Cervex brush sampling, with regard to both adequacy and the presence of endocervical cells.     

Comparative evaluation of seven cell collection devices for cervical smears

OBJECTIVE: To compare the most commonly used cervical sampling devices. STUDY DESIGN: We examined seven cytology sampling devices (Cytobrush, Cervex brush, Szalay spatula, Papex spatula, WrGKK spatula [main social security agency in Vienna], cotton swab and loop). Eight hundred smears were assessed for even distribution of cells, percentage of slide surface covered with cells, and presence and number of endocervical cells. RESULTS: Even distribution of cells was best with the WrGKK spatula. Percentage of slide surface covered with evaluable cells was best with the Cytobrush. Highest ranking for the presence of endocervical cells was found for the Cytobrush. Cotton swabs and loop showed inferior results in all categories. CONCLUSION: The use of cervical cell sampling devices showing the best cytologic results improves the interpretation and validity of cervical smears. Our results suggest that cotton swabs and loops should not be used for cervical cell sampling.     

Exploiting the "toothpick effect" of the Cytobrush by plastic embedding of cervical samples

The introduction of the combined spatula-Cytobrush sampling method has increased the diagnostic accuracy of cervical cytology. However, the smears from a small number of cases contained epithelial fragments dislodged by the "toothpick effect" of the Cytobrush. Due to their thickness, these epithelial fragments in the smears are very difficult (if not impossible) to scrutinize and are thus undiagnosable. The presence of only such fragments in smears led to false-negative diagnoses in two cases of invasive carcinoma. To solve this problem, these epithelial fragments were embedded in plastic, with thin sections prepared from the blocks. This paper presents the morphologic features and diagnostic accuracy of 77 such problem cases (found among 50,000 cases with spatula-Cytobrush smears) to which this method was applied. In almost all cases, the diagnosis on the plastic-embedded sections matched the diagnosis on the colposcopically directed biopsy. Of these 77 patients, the biopsy diagnosis showed 5 severe dysplasias, 6 carcinomas in situ, 1 squamous-cell carcinoma, 2 adenocarcinomas in situ and 2 adenocarcinomas. In addition, data are presented concerning the nuclear-size and shape-factor differences in smears versus plastic-embedded sections, and the stereologic consequences of smearing and cutting these epithelial fragments are discussed. These plastic-embedded sections are well suited for use in quantitative microscopy, as well as for diagnostic purposes.     

Analysis of five sampling methods for the preparation of cervical smears

The quality of the cervical smear, a decisive factor in the efficacy of population screening, can depend on the sampling method utilized. An analysis was made of the performance of five sample takers in a screening program, each of whom had made approximately 5,000 smears, and of the five sampling methods each had used: spatula alone (method A), Cytobrush plus spatula (method B), Cytopick (method C), cotton swab plus spatula (method D) and Cervex brush (method E). The differences between the sample takers and the sampling methods were significant in both the detection of grade III cervical intraepithelial neoplasia (CIN III) (P less than .01) and in the production of smears containing endocervical cells (EC+) (P less than .018). The data obtained firmly establish the importance of the presence of endocervical cells for smear adequacy. The results of this study indicate that (1) method B (Cytobrush plus spatula) and method C (Cytopick) give superior results in the preparation of EC+ smears and in the detection of CIN III and thus should be used in population screening programs, and (2) methods A and D should not be used for cervical cytologic sampling in such programs.     

Relation between sampling device and detection of abnormality in cervical smears: a meta-analysis of randomised and quasi-randomised studies.

OBJECTIVE: To assess the diagnostic yield of different sampling devices used in cervical screening. DESIGN: Meta-analysis of randomised and quasi-randomised studies. SETTING: All randomised and quasi-randomised studies comparing the yield of cytological or histological abnormalities when two or more different sampling devices were used. SUBJECTS: 85,000 patients included in 29 studies reported in 28 papers. MAIN OUTCOME MEASURES: Pooled relative risk and 95% confidence interval of the yield of mild dysplasia or worse in smears recovered by each sampling method versus each other method with which it was compared; sensitivity or positive predictive value, or both, of cytological versus histological results in six studies from which sufficient data were available. RESULTS: There were no substantial differences in the yield of cytological abnormalities between the Ayre spatula, the Cytobrush, and the cotton swab used alone. There were also no substantial differences in the yield of cytological abnormalities between the extended tip spatula, the Ayre spatula combined with the Cytobrush or cotton swab, or the Cervex brush. The Ayre spatula, Cytobruah, or cotton swab used alone generally performed significantly worse than the combinations, the extended tip spatula, or the Cervex brush. There were no substantial differences in sensitivity or positive predictive value between the sampling methods. CONCLUSIONS: These results support the use of either the extended tip spatula, a combination of any spatula plus the Cytobrush or cotton swab, or the Cervex brush for cervical screening.     

Improved endocervical sampling with the Cytobrush.

OBJECTIVE: To evaluate the effectiveness of the Ayre wooden spatula, the cotton-tipped swab and the Zelsmyr Cytobrush in obtaining endocervical cells. DESIGN: Cross-sectional comparison study. SETTING: Family practice unit. PATIENTS: All postpubertal, nonpregnant women who underwent a routine Papanicolaou smear during a 7-month period. INTERVENTIONS: The three devices were used in each patient in a randomized sequence. An experienced cytotechnologist blinded to the device used evaluated the slides for overall epithelial cellularity (graded from 0 [acellular specimen] to 12 [overloaded sample]), density (the number of groups of five or more endocervical cells) and size of cell clusters (5 to 10 cells per cluster [score of 1], 11 to 100 [2] or more than 100 [3]). MAIN RESULTS: Samples from 2 of the 136 women were rejected because of improper labelling of the slides or failure to use all three devices. Seventy-six (57%) of the smears obtained with the spatula and 71 (53%) with the swab had no endocervical cells, as compared with only 14 (10%) obtained with the Cytobrush (p = 0.001). The overall cellularity (and standard deviation [SD]) of the smears obtained with the Cytobrush (5.69 [SD 1.17], p = 0.001) and the spatula (5.70 [SD 1.46], p = 0.001) was significantly greater than the cellularity of those obtained with the swab (4.31 [SD 1.17]). The Cytobrush yielded significantly more groups of endocervical cells (109.84 per slide) than either the spatula (4.17) or the swab (6.25) (p = 0.001). The Cytobrush also produced larger cell clusters (1.56 [SD 0.67], p = 0.001) than either the swab (0.83 [SD 1.70]) or the spatula (0.64 [SD 0.67]). CONCLUSIONS: The Cytobrush and the spatula should be used instead of the spatula alone or the spatula and the swab for collecting endocervical cells.     

Pap smear quality parameters of 3 sampling devices used by auxiliary nurse midwives on symptomatic rural Indian women

OBJECTIVE: To determine whether auxiliary nurse midwives (ANMs) could make good-quality Pap smears after focused training and to determine which sampling device is most effective in their hands in field practice areas. STUDY DESIGN: In a downstaging cervical cancer screening program, 394 symptomatic rural Indian women between the ages of 35 and 60 were identified by the ANMs in 2 villages, with a total population of 14,747, and were invited to have a smear taken. Two hundred of these symptomatic women responded. The ANMs were educated to render information on screening for cervical cancer and to take smears with 3 sampling devices--Ayre spatula, modified spatula (with extended tip) and Cytobrush (Medscand AB, Malm?, Sweden). The smears were evaluated for 6 adequacy parameters. Smears made by gynecologists were used as controls. To establish the superiority of a method, chi2 tests were used. RESULTS: All smears made by the ANMs could be used to render a cytologic diagnosis. The adequacy parameters of all the smears made by ANMs at least matched those of the gynecologists. The best results were obtained with modified spatula (with extended tip) and combination of Cytobrush with modified spatula. CONCLUSION: Since only 50% of symptomatic rural women came for Pap testing, we conclude it is not easy to motivate women for such testing, even if a large-scale educational effort is made. ANMs can be taught to take reasonably good qualisuperior sampling device for ANMs is ty Pap smears. The superior sampling device for ANMs is the modified spatula (with extended tip).     

Use of the Cytobrush for cervical sampling after cryotherapy

The presence of endocervical cells in routine gynecologic smears (prepared from spatula and cotton swab samples) and Cytobrush smears was analyzed in 52 patients with a history of prior cryotherapy. These cases represented 11% of the 491 women evaluated using both techniques between August 1, 1987, and January 31, 1990. The routine smear contained endocervical cells in 25 (48%) of the 52 cases while the Cytobrush smear contained endocervical cells in 49 (94%) of the cases. The use of the Cytobrush for cervical cytologic screening thus appears to be of value in patients with a prior history of cryotherapy, which frequently renders the transformation zone less accessible to routine sampling.     

Cytobrush and wooden spatula for oral exfoliative cytology. A comparison.

The Cytobrush has been used frequently in cervical cytology, but as yet its value in oral exfoliative cytology has not been assessed. A study was undertaken to compare the efficiency of the Cytobrush with that of the wooden tongue spatula. For 26 patients, two smears were collected from clinically normal mucosa from four sites in the oral cavity (buccal mucosa, dorsal tongue, ventral tongue and hard palate). The smears were graded for cell yield and dispersion on a three-point scale. The results were analyzed using the chi 2 test. The Cytobrush was found to be significantly more efficient than the wooden spatula, in terms of both cell yield (P less than .005) and cell dispersion (P less than .005). When each site was examined separately, the Cytobrush produced significantly better dispersion for the dorsal tongue, ventral tongue and buccal mucosa and a better cell yield for the tongue surfaces. No significant difference for cell yield or dispersion was found for the hard palate. The study showed that the Cytobrush is an effective instrument for use in exfoliative cytology of normal oral mucosa.     

Efficacy of the cytobrush versus the cotton swab in the collection of endocervical cells

Cervical smears should contain endocervical cells to be accepted as adequate for a cytologic diagnosis. Before this study was undertaken, one-third of the smears received in the Cytology Laboratory of Odense University Hospital were inadequate. In an attempt to increase the rate of adequate smears, a randomized study was undertaken to compare the efficacy of the combined spatula-Cytobrush method to that of the spatula-cotton swab method traditionally used by doctors in Denmark. The incidence of smears containing cylindrical and/or metaplastic cells was 89% by the spatula-Cytobrush method as compared to 62% by the spatula-cotton swab method (P less than .001). There were large differences between the rates of adequate smears from the various doctors when using the spatula-cotton swab method (range, 14% to 82%); these differences were far less when using the spatula-Cytobrush method (range, 75% to 100%). A large-scale application of the spatula-Cytobrush method should result in fewer repeat smears required and fewer false-negative smears.     

The efficiency of the Cytobrush versus the cotton swab in the collection of endocervical cells in cervical smears

In 30 patients whose last cervical smear had lacked endocervical cells, two new samples were collected, one with a cotton-tipped applicator and the other with the recently developed Cytobrush cervical brush. With the cotton swab, no endocervical cells were present in the repeat smears of 21 patients, as compared with only 3 Cytobrush smears lacking endocervical cells; the difference is statistically significant (P less than .001). Quantitatively, the cellular yield with the Cytobrush was larger. It is concluded that the use of the cervical brush to collect material for cervical smears is more effective and provides a higher yield of cells than the use of the conventional cotton swab. The importance of the presence of endocervical cells in a smear as evidence that the transformation zone has been properly sampled is also discussed.     

A comparison between the Accu-Pap device and the extended-tip wooden Ayre spatula for cervical cytology sampling

The wooden Ayre spatula with an extended endocervical tip was compared with both designs of the plastic Accu-Pap sampler in two series of 100 consecutive patients to compare their adequacy in obtaining samples for cervical cytology. There was no significant advantage noted in the smears taken by either spatula. In terms of the sequence of smears, the second smear generally contained more endocervical cells and less often showed an absence of diagnostic cells.     

Cytohistologic correlation between AGUS and biopsy-detected lesions in postmenopausal women

OBJECTIVE: To evaluate histologic findings in patients aged 50 and older whose cervical smears revealed atypical glandular cells of undetermined significance (AGUS). STUDY DESIGN: Computerized records spanning a four-year period were retrospectively analyzed. Thirty patients over age 50 had cervical smears interpreted as AGUS and had follow-up biopsies within 12 months following the abnormal smear. The most important histologic diagnosis from the biopsy specimens was correlated with the subcategory of the cervical smear. RESULTS: Five smears interpreted as AGUS, favor reactive, revealed abnormal histology in four cases: three endometrial polyps and one squamous carcinoma. Two smears interpreted as AGUS, favor dysplasia, revealed squamous intraepithelial lesions on biopsy in both cases. Seventeen smears interpreted as AGUS, favor endometrial cells, revealed abnormal histology in 13 cases: 1 endocervical polyp, 6 endometrial polyps, 3 endometrial hyperplasias and 3 adenomyosis. Six patients with smears interpreted as AGUS, unclassifiable, revealed abnormal histology in five cases: two endocervical polyps, one endometrial polyp, one endometrial carcinoma and one ovarian carcinoma. CONCLUSION: The presence of AGUS in cervical smears from women over 50 was highly predictive of abnormal lesions detected by histologic examination. Although three cancers were detected on histologic follow-up, the most common lesions detected were endometrial polyps.     

Controlled trial of a new cervical spatula.

A wooden spatula was designed to scrape the varied distribution of epithelial abnormalities of the cervix as seen at colposcopy. The efficiency of the spatula in obtaining dyskaryotic cells and improving the cellular quality of smears was compared with that of the Ayre spatula in a controlled trial. More than 17,000 smears were taken from women aged 14-86 years by more than 200 smear takers from 74 centres. Twenty two per cent more dyskaryotic smears were obtained with the trial spatula, and the cellular quality of the smears was improved in all age groups. Although it was associated with a slightly increased risk of bleeding, 83% of users preferred the trial spatula.     

Collection devices for cervicovaginal cytology: a comparison

OBJECTIVE: To compare cervicovaginal smears obtained by a cotton-tipped swab with those obtained by cervix brush and modified Ayre spatula. STUDY DESIGN: A combined cervicovaginal smear was collected from 100 women using 3 different collection devices: cotton-tipped swab, cervix brush, and modified Ayre spatula. In each patient a set of 3 smears was collected by the same cytotechnologist using all 3 devices in random order. Smears were evaluated using parameters mandatory for an optimal smear: evenly dispersed, well-preserved, adequate cells from the transformation zone. The cost and availability of the collection devices were also considered. RESULTS: The swab was the most effective device in obtaining thin, evenly spread, adequate, well-preserved smears as against the cervix brush and Ayre spatula. The pickup of abnormal cells was similar with the cotton-tipped swab and cervix brush, while the Ayre spatula failed to yield high grade squamous intraepithelial lesions, atypical glandular cells of undetermined significance and adenocarcinoma cells. The cotton-tipped swab proved to be the most cost effective. CONCLUSION: A properly prepared cotton-tipped swab is an inexpensive, readily available, nontraumatic collection device that yields smear of optimal quality.     

Significance of cytologically normal endometrial cells in cervical smears from postmenopausal women

OBJECTIVE: To determine the significance of cytologically normal endometrial cells in cervicovaginal (CV) smears from postmenopausal women over age 55 years. STUDY DESIGN: From January 1995 to January 1998, 220 women had CV smears demonstrating cytologically normal endometrial cells. The menopausal status, hormone replacement therapy (HRT) and information related to subsequent CV smears and endometrial sampling within 12 months of the initial diagnosis was recorded. RESULTS: Eighty-one of the 220 cases (36.8%) had histologic sampling of the endometrium. Thirty-four of 81 (42%) showed no endometrial pathology. Endometrial pathology was identified in 28 of 81 (34%), of which 19 were endometrial polyps (23.4%), 4 were endometrial hyperplasia (4.9%), 4 were endometrial carcinoma (4.9%) and 1 was a leiomyoma (1.2%). Nineteen (23.4%) were insufficient for diagnosis. Ninety-one of 220 women were on HRT, and 129 were not. In the group without HRT, endometrial disease was identified in 22/51 (43%) cases as compared to 6/30 (20%) in the group with HRT (P < .001). Endometrial carcinoma was identified in three (5.8%) cases and one (3.3%) case without and with HRT, respectively. CONCLUSION: Although the finding of normal endometrial cells in Pap smears from postmenopausal women was without any clinical significance in the majority of women in this study, in a small number it was associated with endometrial hyperplasia and carcinoma. Women who were not on HRT had a higher incidence of endometrial pathology.     

Aylesbury and cervitula spatulas: a comparative study to assess the adequacy of cervical smears

OBJECTIVE: To assess whether the Aylesbury (Pharmaceutical Enterprises Ltd., Pinelands, Capetown, South Africa) or Cervitula spatula (Harwill Medical, Capetown, South Africa) is more effective for adequate cervical smears in obstetric and gynecology patients. STUDY DESIGN: The Cervitula spatula was compared with the Aylesbury spatula by taking a total of 160 smears, which were examined cytologically. This consisted of 40 obstetric and 40 gynecology patients. The sequence in which the spatiulas were used was determined by computer randomization. Our main outcome criterion was whether both ectocervical and endocervical cells were present, thus making the smear adequate. Our numbers were too small to draw conclusions on the cytologic abnormalities detected between the two spatulas. RESULTS: The Cervitula was more effective for the identification of endocervical cells in obstetric patients (P = .0008). When combining the obstetric and gynecology groups, the Cervitula was also better in obtaining endocervical cells, but this did not reach statistical significance (P = .016). CONCLUSION: Pap smear sampling with the Cervitula reduces the number of cases without endocervical cells, which would constitute an inadequate smear, requiring unnecessary recall of patients for repeat smears.