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.     

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.     

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.     

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.     

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.     

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.     

Cervex-Brush vs. spatula and Cytobrush. A cytohistologic evaluation

OBJECTIVE: To compare the efficacy of two cervical smear instruments, Cervex-Brush and spatula plus Cytobrush. STUDY DESIGN: Cervical smears were taken before laser ring biopsies in 213 women, who were randomized for the Cervex-Brush or spatula plus Cytobrush (S+C). The cytologic diagnosis was compared to the histologic diagnosis after laser ring biopsy. RESULTS: The correlation between cytology and histology showed comparable concordance (54% and 42%) for the two devices. In 130 (74 with Cervex-Brush and 56 S+C) patients, histology revealed moderate dysplasia or more advanced lesions. Those cases were further analyzed for smear failures. Negative smears were found in 13 cases (10 in the Cervex-Brush and 3 in the S+C group). This difference in favor of S+C was not, however, statistically significant. Significantly more false negative smears were found when endocervical cells were absent and in patients 30-39 years of age. CONCLUSION: Modern sampling devices, such as the Cervex-Brush and S+C, seem to be equally efficient in obtaining dysplastic squamous cells. Other factors of importance for nonrepresentative cervical smears should be studied in order to improve efficacy.     

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.     

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.     

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.     

Frequency of endocervical cells in cervical smears and hysterectomy rate of the patients

In gynecologic cytology, different reporting schemes suggest mentioning the presence of endocervical cells or asking for a statement on adequacy. We were interested in the question whether our data could provide a possible basis for discussing a sampling technique with smear takers. At the time of writing, in all cases, both the presence of endocervical cells and hysterectomy are recorded in our laboratory information system. Most smears are taken with cotton swabs, but the sampling technique is often modified according to the clinical situation. In a series of 20,471 cervical/vaginal smears, 2,152 (10.5%) were taken from hysterectomy patients. Among the non-hysterectomy patients, endocervical cells were found in 65% of the cases. Typically, there was a lower frequency of endocervical cells in smears stemming from older women. The frequency decreased from a maximum of 75% in the age group of 40-44 years to 45% in the age group of 65-69 years. With regard to the smear takers, some differences were evident, with age distribution and frequency of hysterectomy being different among the smear takers. In a setting where many smears of hysterectomized patients are examined by cytology, good data quality is required to evaluate the sampling techniques of different smear takers. The age dependence of endocervical cell yield is confirmed. Different age distribution of the patients from different smear takers suggests that the percentage of smears showing endocervical cells cannot be considered an optimal estimator.     

Diagnostic cytology for detection of early cancer

Cytologic methods for detection of early cancers of the uterine cervix, lung and various other organs are discussed. The scraping smear method using a spatula is more effective than the cotton swab or vaginal pool smear method for detection of preinvasive intraepithelial lesions, such as, carcinoma in situ and dysplasias of various degrees of the uterine cervix. The use of sputum specimens pooled for three to five days is recommended for cytologic examination in population screening of lung cancer. Good cytopreparatory techniques, suitable screening and cytodiagnostic classifications of malignancy are also described and emphasized, especially, the importance of properly fixed cytologic material for correct cytopathological diagnosis.     

The in situ polymerase chain reaction for detection of chlamydia trachomatis

The in situ polymerase chain reaction (PCR) is a technique that has important applications in the diagnosis of viral and bacterial diseases. This study investigated an in situ PCR assay established to detect the presence of Chlamydia trachomatis in endocervical swabs. In addition, histological sections of endocervical squamous cell carcinoma were analyzed because previous studies had revealed a significant association with C. trachomatis. A total of 20 cervical neoplasms (squamous cell carcinoma in situ; n = 10; invasive squamous cell carcinoma; n = 10) and endocervical smears taken from five patients with and without inflammatory changes were analyzed by conventional PCR. Chlamydial DNA was found in 10 histological samples (six carcinomas in situ, four invasive carcinomas) and in one endocervical swab from a patient with known C. trachomatis infection. Positive specimens were used for establishing an in situ PCR assay (IS-PCR). After IS-PCR, these samples showed dense cytoplasmic staining of endocervical cells (smears) and non-neoplastic epithelial cells (cervical neoplasms). The other tumor samples and smears did not demonstrate positive PCR reaction. The results indicate that in situ PCR is an effective technique for localizing C. trachomatis in target cells because IS-PCR detection of chlamydial DNA correlated with histological and cytological features.     

Conservative management of options for patients with dysplasia involving endocervical margins of cervical cone biopsy specimens

OBJECTIVE: Our purpose was to study the feasibility of conservatively managing selected cases of dysplasia involving endocervical cone margins. STUDY DESIGN: A retrospective review of patients conservatively managed after being found to have squamous cell dysplasia involving the endocervical margins of their cervical cone biopsy specimens. In phase I patients who had cold-knife conization with positive endocervical margins underwent repeat Papanicolaou smears and colposcopy, with biopsies and endocervical curettage as indicated. Those found free of disease were followed up with frequent Papanicolaou smears. In phase II patients with dysplasia to the endocervical resection edges on loop electrical excision procedure biopsy specimens were followed up with frequent cytologic studies. RESULTS: In phase I, 31 patients with positive endocervical margins on cold-knife conization and no evidence of dysplasia on reevaluation were followed up for 1 to 18 years. Dysplasia was detected in one patient during cytologic surveillance. In phase II, 11 patients were followed up for 12 to 31 months; only one patient has dysplasia. CONCLUSION: Selected patients with squamous cell dysplasia at endocervical cone biopsy margins may avoid additional surgery.     

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.     

The detection of endocervical gland involvement by high grade squamous intraepithelial lesions in smears prepared from endocervical brush specimens

The cytologic features of squamous cell carcinoma in situ with endocervical gland involvement have been described in cervical smears. We evaluated the presence of two types of cellular fragments in 43 cervical smears of high grade squamous intraepithelial lesions (HGSIL) to assess their ability to predict glandular involvement by HGSIL in subsequent cone biopsies. An endocervical brush was used to obtain all endocervical specimens. Of 16 cases without glandular involvement, fragments were present in 13 smears. Of 27 cases with glandular involvement, fragments were absent in 11 smears. No statistical association was identified between the presence of abnormal cellular fragments on cervical smears of HGSIL and endocervical gland involvement on cone biopsies.     

Pap smear screening in an urban STD clinic. Yield of screening and predictors of abnormalities

BACKGROUND: Pap smear screening studies in STD clinics have reported high rates of squamous intraepithelial lesions (SIL); however, there are limited data on levels of unsatisfactory smears of characteristics associated with cytologic abnormalities. GOAL: To assess the yield to Pap smear screening in an STD clinic and to evaluate the rates of and risk factors for atypia, low-grade SIL (LSIL), and high-grade SIL (HSIL). STUDY DESIGN: A chart review of the clinic records of women undergoing Pap smear screening between 1991 and 1994 was conducted. Results were assessed from two different screening protocols, the first using a Dacron swab to obtain the endocervical sample and the second using a cytobrush. RESULTS: Of 2034 Pap smears, 1313 (64.6%) were negative, 202 (9.9%) were unsatisfactory, 257 (12.6%) were atypical, 211 (10.4%) had LSIL, and 51 (2.5%) had HSIL. With the change to the cytobrush protocol, the rate of unsatisfactory smears decreased from 14.4% to 3% (p < 0.001), atypia increased from 10% to 16.7% (p < 0.001), and HSIL rose from 1.7% to 3.7% (p < 0.001). By multivariate analysis, atypia was associated with genital warts (odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02); LSIL with younger age (p < 0.001, for trend), black race (OR 1.51, 95% CI: 1.08-2.10), genital warts (OR 1.81, 95% CI: 1.33-2.47), and an abnormal appearance of the cervix on examination (OR 2.49, 95% CI: 1.85-3.35); and HSIL with a previous abnormal Pap smear (OR 2.48, 95% CI: 1.08-2.10). Overall, abnormality rates were significantly higher in adolescents (35.5%) than older women (21.7%) (p < 0.01). CONCLUSIONS: Obtaining satisfactory Pap smears among women undergoing screening in an STD clinic is feasible and cytologic abnormalities are common. These results continue to support the need for Pap smear screening in STD clinics, but the high rates in adolescents, a group in whom the natural history of cytologic abnormalities has not been well-defined, raise questions about the need to develop age-appropriate screening and management strategies.     

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.     

Desulphation of heparin by mice and guinea pig leukocytes

A series of 603 patients referred with atypical Papanicolaou smears was evaluated by repeat smears, colposcopically directed cervical biopsies, and endocervical curettage. These techniques as a unit can establish an accurate outpatient diagnosis superior to any of these modalities used alone and comparable with findings in conization and hysterectomy specimens. Endocervical curettage has made a unique contribution to the evaluation of such patients; these curettings have allowed examination of tissue fragments and are more reliable in diagnosing neoplasia than are endocervical smears. Invasive carcinoma and its precursors confined to the anatomic endocervical canal can be recognized by this technique, and conversely the absence of neoplastic epithelium in adequate endocervical curettings rules out occult carcinoma. Indications for conization of the cervix are discussed in reference to the other biopsy and cytologic findings, and guidelines are presented for patient management, stressing clinicopathologic correlation and cooperation.     

Lower moiety heminephroureterectomy in the duplex refluxing kidney: the accuracy of isotopic scintigraphy in functional assessment

OBJECTIVE: To estimate the incidence of dysplasia in patients with Papanicolaou smears showing atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (SIL) and to identify clinical predictors of dysplasia in these patients. METHODS: Patients referred for ASCUS and low-grade SIL were reviewed retrospectively. All patients were evaluated with immediate colposcopy. A multivariate logistic regression analysis was performed to identify clinical predictors of histologic SIL and histologic high-grade SIL. RESULTS: One hundred thirty-seven (34%) of 406 consecutive patients had histologic SIL. Regression analysis identified age (under 35 versus 35 years or above) and initial smear (low-grade SIL versus ASCUS) as statistically significant predictors of histologic SIL and high-grade SIL (P < .001). When patient outcomes were analyzed by age and initial Papanicolaou smear results, the subgroup of patients 35 years or older with ASCUS had low incidences of histologic SIL (14%) and high-grade SIL (1%). The other subgroups (under 35 years with ASCUS, under 35 years with low-grade SIL, and 35 years or older with low-grade SIL) had incidences of histologic SIL and histologic high-grade SIL of at least 28% and 14%, respectively. CONCLUSION: The high incidence of dysplasia in patients with minimally abnormal Papanicolaou smears suggests that immediate colposcopy might be appropriate for many of these patients. Age and initial Papanicolaou smear are predictive of dysplasia and might be used to select patients who have low incidence of dysplasia and might not require immediate colposcopy.