A randomized comparison of the 3 Papanicolaou smear collection methods

The purpose of this study was to compare the effectiveness of 3 cervical smear sampling devices for obtaining acceptable yields of endocervical cells in Papanicolaou smears. In a randomized, controlled clinical trial, we collected 346 smears over a 6-month period, 110 with the Cervex brush, 125 with the cotton swab plus Ayre spatula and 111 with the Cytobrush plus Ayre spatula. The Cytopathology Laboratory, blinded to the Papanicolaou smear method, screened the smears using the Bethesda system guidelines. Statistical analyses were performed using the Pearson X2 and analysis of variance tests. There was an increased detection of endocervical cells in the Cytobrush plus Ayre spatula and the Cervex brush methods, compared with the cotton swab plus Ayre spatula group (p = 2.39 x 10(-6), p = 4.49 x 10(-7) respectively). There was no statistically significant difference between the Cytobrush-Ayre spatula and the Cervex brush sampling methods were equally effective in obtaining endocervical cells in Papanicolaou smears.     

Safety, efficacy and cost of three cervical cytology sampling devices in a prenatal clinic

OBJECTIVE: To evaluate and compare the safety, efficacy and cost of three cervical cytology sampling devices in pregnant women presenting for prenatal care to the obstetrics clinic, at Medical College of Pennsylvania Hospital. STUDY DESIGN: From September 7, 1993, to November 5, 1993, 61 cervical cytologic smears were obtained using the Cell-Sweep. From November 8, 1993, to January 7, 1994, 66 smears were obtained using the Ayre spatula/Cytobrush, and from January 10, 1994, to February 18, 1994, 55 smears were obtained using the Ayre spatula/cotton swab. The rate of smears with no endocervical component or with epithelial cell abnormality was determined for each group. The patients' medical records were reviewed retrospectively to determine complications occurring within two weeks of smear collection. RESULTS: Fifteen (25%) smears in the Cell-Sweep group, one (1.5%) in the Cytobrush group and nine (16%) in the cotton swab group were satisfactory but limited by absence of an endocervical component (P < .0006). None of the smears were unsatisfactory. Eleven (18%) smears in the Cell-Sweep group, eight (12%) in the Cytobrush group and nine (16%) in the cotton swab group revealed an epithelial cell abnormality (P = .643). For all three groups there was a low rate of spontaneous abortion, preterm spontaneous rupture of membranes or preterm labor occurring within two weeks of collection. There was no statistically significant difference in these complications between the three groups (P = .7). The Ayre spatula/cotton swab is the least expensive device. CONCLUSION: The Ayre spatula/cotton swab was the most satisfactory of the three methods tested for obtaining cervical cytology during pregnancy. It is safe and cost-effective and identifies the same proportion of epithelial cell abnormalities as the Ayre spatula/Cytobrush and the Cell-Sweep.     

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.     

Biological relevance and consequences of chemical- or metal-induced DNA cross-linking

A prospective, randomized clinical trial was conducted to study the safety and efficacy of the Cytobrush for Papanicolaou smear screens in 252 pregnant women. Two groups-Ayre spatula plus Cytobrush and Ayre spatula plus cotton swab-were compared. There was a higher incidence of spotting with each of the three devices as compared with studies of nonpregnant women. The highest incidence of spotting at time of exam occurred with the Cytobrush; however, this spotting was not clinically significant. Eleven first-trimester women experienced a pregnancy loss; five of these losses were due to a hydatidiform mole or missed abortion that occurred before the exam. Six women (2%) aborted spontaneously compared with a 10% incidence reported in the literature. It was concluded that all three devices are safe for use in pregnancy. In addition, the most adequate screen for retrieval of squamous epithelial cells was found to be the Ayre spatula, while the Cytobrush proved most effective for retrieval of endocervical epithelial cells.     

A trial of two methods of taking cervical smears: the Aylesbury spatula plus cytology brush compared to the Cervex broom

AIMS: To compare the adequacy of cervical smear taking, using the Aylesbury spatula plus cytology brush with the Cervex broom. METHODS: Two cervical smears were taken at the same visit, the women acting as their own controls. In Group 1 comprising 81 women, the first smear was taken using the Cervex broom. In Group 2 comprising 97 women, the first smear was taken using the Aylesbury spatula followed by the cytology brush. The tips of the samplers were sent to the laboratory in a cytology container with 30% ethyl alcohol in saline, for analysis of residual cells. RESULTS: It took experienced staff two or three smears before they were adept at taking an adequate Cervex broom sample as defined by the presence of endocervical cells. Both techniques were equally good at detecting significant abnormalities. When the Cervex broom was used first there were more smears with no blood present but when bleeding occurred there was no significant difference between the two groups. Both techniques were well accepted by the women. CONCLUSIONS: Although it is more expensive than the Aylesbury spatula and the cytology brush the Cervex broom has the advantage of allowing a simple one step procedure, thereby reducing the potential for air drying.     

A continuous quality improvement project to improve the quality of cervical Papanicolaou smears

OBJECTIVE: To improve the quality of cervical Papanicolaou smears by continuous quality improvement techniques. METHODS: The study used a Papanicolaou smear data base of over 200,000 specimens collected between June 1988 and December 1992. A team approach employing techniques such as process flow-charting, cause and effect diagrams, run charts, and a randomized trial of collection methods was used to evaluate potential causes of Papanicolaou smear reports with the notation "inadequate" or "less than optimal" due to too few or absent endocervical cells. Once a key process variable (method of collection) was identified, the proportion of Papanicolaou smears with inadequate or absent endocervical cells was determined before and after employment of a collection technique using a spatula and Cytobrush. We measured the rate of less than optimal Papanicolaou smears due to too few or absent endocervical cells. RESULTS: Before implementing the new collection technique fully by June 1990, the overall rate of less than optimal cervical Papanicolaou smears ranged from 20-25%; by December 1993, it had stabilized at about 10%. CONCLUSION: Continuous quality improvement can be used successfully to study a clinical process and implement change that will lead to improvement.     

Quality grading for cervical smears

Three thousand five hundred and eighty cervical smears were taken in 1990-1992 at a Genitourinary Medicine Clinic with various spatula or spatula brush combinations. The unsatisfactory rate and the detection of cellular abnormalities showed some relation to spatula type. However, the satisfactory smears screened in the laboratory are routinely assigned a quality grade-good, fair or poor. Analysis shows higher rate of detection of cellular abnormalities in good quality smears, the detection of dyskaryosis being twice as high, in contrast to the fair or poor quality smears. It is suggested that quality grade is a better way of classifying smear quality in the cervical screening programmes rather than the presence or absence of endocervical and/or metaplastic cells.     

Reducing the threat: an experiential exercise to introduce role play to student nurses

OBJECTIVE: To determine if cervical smears obtained with an Ayre spatula and a cytobrush are better detectors of atypia and dysplasia than the modified Ayre spatula alone, as determined by a 2-year clinical follow-up study. METHOD: Paired cervical samples were obtained, one using a modified Ayre spatula and the other a cytobrush. In those smears with any abnormality, follow-up after 2 years documented subsequent cytologic and/or histologic diagnosis. The statistical relationship between the screening tests and follow-up cytologic diagnosis was investigated. SETTING: Seven hundred ninety-two women, aged 18 years and older, who presented to a family practice residency clinic for Papanicolaou tests. RESULTS: The correlation coefficient for the diagnoses obtained using the modified Ayre spatula and the clinical follow-up was .40 (P = .0008), while the correlation coefficient between the cytobrush samples and the clinical follow-up diagnoses was .25 (P = .04). The kappa statistics indicate statistically significant concordance only between the spatula and the follow-up diagnoses. CONCLUSIONS: Cervical smears obtained with a modified Ayre spatula correlated significantly with the follow-up diagnoses. As cervical sampling tools emerge, they need to be evaluated on the basis of accurate identification of significant clinical disease, not only on the basis of obtaining endocervical cells to avoid unnecessary repetition of screening tests and diagnostic workups.     

Order of endocervical and ectocervical cytologic sampling and the quality of the Papanicolaou smear

OBJECTIVE: To determine whether the order of cell collection, endocervical or ectocervical cells first, has an effect on the quality of the Papanicolaou smear. METHODS: One thousand smears were obtained using an Ayre spatula and an endocervical brush. In 500 cases the endocervical brush was used first, and in 500 cases the spatula was used first. All Papanicolaou smears were collected by resident physicians in our university hospital gynecologic clinics. A smear was considered limited for interpretation for the following reasons: 1) lack of endocervical component, 2) obscured by blood, 3) obscured by inflammation, 4) drying artifact, and 5) too thick. RESULTS: The brush-first group had 405 (81%) adequate smears compared with 410 (82%) adequate smears in the spatula-first group. More smears were obscured by blood when the brush was used first (22 or 4.4% compared with three or 0.6%, P < .001). No endocervical component (ie, metaplastic cells, endocervical cells, or mucus) was found in 29 (5.8%) smears from the brush-first group compared with 45 (9.0%) of the spatula-first group, an insignificant difference. More squamous intraepithelial lesions were found when the spatula was used first (55 or 11% compared with 35 or 7.0%, P < .05). CONCLUSION: The quality of the Papanicolaou smear can be improved by using the Ayre spatula first followed by the endocervical brush. Fewer smears will be obscured by blood, which could result in more squamous intraepithelial lesions being detected.     

Efficacy of ThinPrep preparation of cervical smears: a 1,000-case, investigator-sponsored study

The diagnoses of 1,000 pairs of conventional Papanicolaou (Pap) smears and ThinPrep preparations were compared. Cervical cells were collected using an Ayre spatula and endocervical brush. The conventional smear was made first, the collection devices were rinsed into PreservCyt solution, and the slides were prepared using the ThinPrep Processor. The diagnoses of the paired smears agreed in 988 of the 1,000 cases (98.8%), including 949 negatives, 28 atypicals, 9 low grade squamous intraepithelial lesions (LGSIL), and 2 high grade squamous intraepithelial lesions (HGSIL). Five cases where LGSIL or HGSIL was found on the ThinPrep slide were negative or atypical on the conventional smear. No conventional smear abnormalities were missed on the ThinPrep slide. Although not statistically significant, this difference indicates that the ThinPrep method gives a better diagnosis of abnormalities than the conventional method. The ThinPrep method was acceptable to participating physicians and ThinPreps were easier and faster to screen than conventional smears.     

Screening histories of incidence cases of cervical cancer and high grade SIL. A comparison

OBJECTIVE: To compare the cytologic history of patients with cervical cancer with that of patients with high grade cervical intraepithelial neoplasia (CIN) in order to analyze the causes of screening failure. STUDY DESIGN: In 337 patients treated for high grade CIN and 86 women treated for cancer of the cervix, all cytologic reports from the last five years before diagnosis were reviewed, and slides of normal smears taken within three years of diagnosis were reexamined. RESULTS: Among patients with cancer, 32/86 (37.2%) never had a smear, for 28/86 (32.6%) the time interval between screenings was greater than three years, 12/66 (18.2%) were incorrectly managed after the first abnormal smear, and 7/69 (10.1%) had a normal smear within three years of diagnosis. Conversely, among patients with high grade CIN, 45/337 (13.4%) never had a smear, 60/337 (17.8%) had a time interval between screenings greater than three years, 120/337 (35.6%) were incorrectly managed after the first abnormal smear, and 100/333 (30.0%) had a normal smear within three years of diagnosis. When compared with high grade CIN, cancer of the cervix was associated with absent or insufficient screening (adjusted odds ratio [aOR] = 3.28, 95% confidence interval (95% CI) = 1.86-5.80) but neither with incorrect management of the first abnormal smear (aOR = 1.32, 95% CI = 0.46-3.75) nor with a normal smear within three years of diagnosis (aOR = 0.22, 95% CI = 0.10-0.50). CONCLUSION: Better participation of patients is necessary to improve the efficacy of screening. Conversely, reducing the interval between smears to less than three years would cause a major increase in cost and earlier diagnosis of high grade CIN, but not a significant decrease in the number of cancers.     

Evolution of atypical gynecological cervical smears in a captive population

BACKGROUND: An atypical cervical smear may represent a wide variety of lesions, from banal diseases to invasive neoplastic lesions. AIM: To study the evolution of atypical cervical smears in a highly controlled women population. MATERIAL AND METHODS: A retrospective analysis of 117 women with atypical cervical smears, diagnosed between 1985 and 1994, was performed at the institutional hospital of a mining corporation in Chile. RESULTS: Patients age ranged from 25 to 65 years. Six percent of atypical cervical smears were associated to Papillomavirus infection and 25% to unspecific infectious agents. In the second smear, during follow up, 22.2% of women had some degree of squamous intraepithelial lesion or signs of Papillomavirus infection. A cervical biopsy was performed to 69 women, confirming the presence of a squamous intraepithelial neoplasia or signs of Papillomavirus infection in 38.4% of them. Only one patient had microinvasion. CONCLUSIONS: All patients with atypical gynecological cervical smears should be closely followed to ascertain the diagnosis.     

Significant reduction in the rate of false-negative cervical smears with neural network-based technology (PAPNET Testing System)

False-negative cervical Pap smears may lead to disability or death from carcinoma of the uterine cervix. New computer technology has led to the development of an interactive, neural network-based vision instrument to increase the accuracy of cervical smear screening. The instrument belongs to a new class of medical devices designed to provide computer-aided diagnosis (CADx). To test the instrument's performance, 487 archival negative smears (index smears) from 228 women with biopsy-documented high-grade precancerous lesions or invasive cervical carcinoma (index women) were retrieved from the files of 10 participating laboratories that were using federally mandated quality assurance procedures. Samples of sequential negative smears (total 9,666) were retrieved as controls. The instrument was used to identify evidence of missed cytological abnormalities, including atypical squamous or glandular cells of undetermined significance (ASCUS, AGUS), low-grade or high-grade squamous intraepithelial lesions (LSIL, HSIL) and carcinoma. Using the instrument, 98 false-negative index smears were identified in 72 of the 228 index women (31.6%, 95% confidence interval [CI]: 25% to 38%). Disregarding the debatable categories of ASCUS or AGUS, there were 44 women whose false-negative smears disclosed squamous intraepithelial lesions (SIL) or carcinoma (19.3%; 95% CI: 14.2% to 24.4%). Unexpectedly, SILs were also identified in 127 of 9,666 control negative smears (1.3%; 95% CI: 1.1% to 1.5%). Compared with historical performance data from several participating laboratories, the instrument increased the detection rate of SILs in control smears by 25% and increased the yield of quality control rescreening 5.1 times (P < 0.0001). These data provide evidence that conventional screening and quality control rescreening of cervical smears fail to identify a substantial number of abnormalities. A significant improvement in performance of screening of cervical smears could be achieved with the use of the instrument described in this report.     

Nutrition-related research at USDA''s Eastern Regional Research Center

Forty thousand consecutive cytologic smears and subsequent diagnostic procedures resulted in the diagnosis of 41 carcinomas in situ, 35 microinvasive and invasive carcinomas, and 24 severe dysplasias for a yield of significant neoplasia of one lesion per 400 Papanicolaou smears. Twenty-five of the carcinomas in situ and microinvasive and invasive carcinomas were diagnosed in patients with atypical smears indicating that all patients with persistent atypical smears require evaluation by tissue examination. Seventy-eight percent of the 119 patients subjected to conization either had carcinoma in situ, microinvasive and invasive carcinoma, or significant cervical dysplasia. Post-operative complications following conization were negligible. In addition there were no postconization deleterious effects on three concurrent and nine subsequent pregnancies. A history of gonorrhea places a patient at a higher risk of developing cervical carcinoma. Annual performance of cytologic smear evaluation is indicated in all sexually active women and in all virginal women over 20 years of age.     

Costs of conventional radical radiotherapy versus continuous hyperfractionated accelerated radiotherapy (CHART) in the treatment of patients with head and neck cancer or carcinoma of the bronchus. Medical Research Council CHART Steering Committee

We have compared the results of targeted manual rescreening of 1211 randomly selected smears with the results of PAPNET-assisted rescreening of 1613 cervical smears, containing at least 6.3% low-grade squamous intraepithelial lesion (SIL). PAPNET diagnosis and the targeted rescreening diagnosis were compared with the initial report, issued on the corresponding smear. Reproducibility scores for inadequacy, presence of endocervical and endometrial cells, specific infections and squamous cell abnormalities were determined. The reproducibility scores for the diagnosis of inadequate smears and specific infections were lower with the PAPNET-assisted rescreening. The detection of squamous cell abnormalities was excellent for both methods (> 0.95), with a higher detection rate for false-negative smears with the PAPNET testing system.     

Diagnosis and therapy of cervical intraepithelial dysplasia in Austria: a survey

PURPOSE: To assess the present state of diagnosis, therapy and follow-up of cervical intraepithelial neoplasia (CIN) in Austria. MATERIAL AND METHODS: 100 questionnaires were sent to all departments of Gynecology and Obstetrics in Austria. The anonymous questionnaire consisted of 22 multiple choice questions. It was possible to choose one or more answers by ticking applicable boxes, with the option in individual cases of giving additional information in the form of free text. RESULTS: 55 (55%) departments returned their answered questionnaires, indicating growing consciousness of quality control in medicine. It was found that in the collection of cytologic specimens 67% of the departments used a wooden spatula and cotton swabs. Management of patients with Pap smears indicating low grade squamous intraepithelial lesion (LSIL) and abnormal colposcopy, in 36 (65%) departments consisted of punch biopsy for histological diagnosis. After 3 recurrent Pap smears indicating LSIL, 76% of the hospitals treated such patients by conization, regardless of the histological grade of the lesion. Following inadequate resection of CIN III by conization, operative management of patients was the most commonly used regimen. CONCLUSION: We regard the results of this survey as a basis for the development of further quality management strategies in the prevention, diagnosis and therapy of cervical intraepithelial neoplasia in Austria.     

Evaluation of the ThinPrep Pap test as an adjunct to the conventional Pap smear

OBJECTIVE: To evaluate the ThinPrep Pap test as an adjunct to the conventional Pap smear. DESIGN AND SETTING: Prospectively collected cervical samples were split for independent screening at a large specialised private gynaecological pathology practice in Sydney. MAIN OUTCOME MEASURES: Detection of additional significant abnormalities (cervical intraepithelial neoplasia 1, or more severe); changed management recommendations from "repeat smear in 12 months" or "...six months" to "colposcopy", a reduction in unsatisfactory reports. RESULTS: 35,560 paired (split-sample) conventional and ThinPrep slides were prepared. Significant abnormalities were detected in 724 conventional smears (2%). Additional significant abnormalities were found in 85 ThinPrep slides whose corresponding conventional smear was negative or unsatisfactory even after review, representing a 12% increase in the detection of significant abnormalities. As a result of the addition of ThinPrep, management recommendations were changed from "repeat smear in 12 months" or "...six months" to "colposcopy" for 89 of 1669 women whose conventional Pap smears showed minor non-specific changes or papillomavirus. There were 1258 conventional smears (3.5%) that were unsatisfactory compared with 235 ThinPrep slides (0.7%); for only 74 samples (0.2%) were both slides unsatisfactory. CONCLUSIONS: The addition of the ThinPrep Pap test improves detection and clinical management of cervical abnormalities, and reduces the number of unsatisfactory samples which would otherwise require repeat tests.     

Hantavirus pulmonary syndrome treated with inhaled nitric oxide

BACKGROUND: A retrospective study was done to assess the correlation between endometrial cells on routine cervical cytology and carcinoma of the endometrium. METHODS: In a 4-year period, endometrial cells of some type were identified on the Papanicolaou (Pap) smears of 61 women, of whom 52 had further diagnostic evaluation of the endometrium. Data were analyzed with a multivariate stepwise logistic regression. RESULTS: The results indicated an association of endometrial cells in Pap smears with carcinoma of the endometrium in seven patients (13.5%). In 45 patients (86.5%), the final diagnosis was benign. Factors that impacted the diagnosis of carcinoma were the findings of atypical or cancerous endometrial cells on Pap smear and abnormal vaginal bleeding. CONCLUSIONS: These data indicate the importance of further diagnostic evaluation with endometrial sampling in postmenopausal patients with endometrial cells seen in Pap smears, especially those with abnormal bleeding.     

Cervical cytology findings in women infected with the human immunodeficiency virus

It has been suggested that immunocompromised, HIV-infected patients are at risk of developing HPV infection and SIL. The well documented role of HPV and SIL in cervical carcinogenesis should lead to frequent, careful evaluation of HIV infected women. Forty-four cervical smears from 23 patients (20 HIV and 3 AIDS) were reviewed. While 11 of the 23 patients produced negative smears, 11 had abnormal cytological findings on at least one occasion. Sixteen smears (36 percent) from 10 patients (43%) showed evidence of HPV and/or SIL. Two smears (two patients) were assigned to the benign epithelial atypia category. (One of these showed keratosis which may indicate HPV infection.) Six smears (three patients) represented either a severe Trichomonas, fungal (Candida sp.), or Herpes infection. Three smears were deemed unsatisfactory for diagnosis due to severe acute inflammation or obscuring blood. Five biopsies were available. In four, histologic findings supported the original cytologic diagnosis. One patient with a negative smear had a biopsy showing condyloma. This study further supports an association of HPV and/or cervical dysplasia with HIV. Careful evaluation and follow-up of HIV-infected women is essential.     

An economic evaluation of patch testing in the diagnosis and management of allergic contact dermatitis

AIM: To investigate the value of RNA detection by nucleic acid sequence based amplification (NASBA) for the monitoring of Chlamydia trachomatis infections after antibiotic treatment. METHODS: Cervical smears (n = 97) and urine specimens (n = 61) from 25 C trachomatis positive female patients were analysed for the presence of C trachomatis 16S ribosomal RNA (rRNA) by NASBA and C trachomatis plasmid DNA by the polymerase chain reaction (PCR) before and up to five weeks after antibiotic treatment. RESULTS: Chlamydia trachomatis RNA was found in all cervical smears taken before antibiotic treatment (n = 24) and in two smears taken one week after antibiotic treatment; no C trachomatis RNA was detected after two weeks or more. In contrast, C trachomatis DNA was found in all such specimens before treatment, and 21 of 25, six of 21, and five of 20 smears were found to be positive at one, two, and three weeks after treatment, respectively. After four weeks, only one of six smears was positive, and this smear had been negative in the two preceding weeks. Of the 61 urine samples investigated, C trachomatis DNA and C trachomatis RNA were found in all before treatment (n = 15), whereas one week after treatment four of 15 were C trachomatis DNA positive and C trachomatis RNA was detected in one sample only. CONCLUSIONS: These data show that RNA detection by NASBA can be used successfully to monitor C trachomatis infections after antibiotic treatment. Furthermore, it might be possible to use urine specimens as a test of cure because neither C. trachomatis DNA or RNA could be detected two weeks or more after treatment.