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.     

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.     

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.     

Does the menstrual cycle and use of oral contraceptives influence the risk of low back pain? A prospective study among female soccer players

BACKGROUND: There is an increasing number of articles regarding the long term follow-up of Papanicolaou (Pap) smears with the diagnosis of atypical squamous cells of undetermined significance (ASCUS). Much controversy exists regarding the management of patients with this diagnosis. In a prior study in 1992, the authors performed automated rescreening of 101 ASCUS cases and 91 negative (control) cases. They found that through PAPNET-directed rescreening, 35 of 101 ASCUS cases (35%) could be reclassified as a squamous intraepithelial lesion (SIL). METHODS: These 192 women were followed since 1992 through manual look backs of subsequent Pap smears and surgical biopsies over a 4-year period. The population studied was comprised of predominantly black women between the ages of 14 and 85 years. The majority were considered a high risk population because many had a history of several sexual partners and multiple pregnancies. RESULTS: Eighteen of 74 patients (24.3%) with an original diagnosis of ASCUS were found on subsequent Pap smears to have an SIL. Only 4 of 64 patients (6%) who originally had a negative Pap smear subsequently were found to have a low grade squamous intraepithelial lesion (LGSIL) within 4 years. Through ordinal logistic regression analysis, it was found that patients with an ASCUS diagnosis had a risk of developing SIL that was 2.6 times greater than the risk for patients with a negative smear diagnosis. Comparing the surgical biopsies in the control and ASCUS groups, there was no statistically significant difference in the risk of developing SIL. This may be because the number of follow-up biopsies were small. CONCLUSIONS: A statistically significant difference of the risk of developing SIL exists between patients with a negative smear versus those with an ASCUS smear. Long term follow-up is essential in the management of the patients with an ASCUS smear because there is clearly an increased risk of developing SIL.     

Structure and fragmentation mechanisms of isomeric T-rich oligodeoxynucleotides: a comparison of four tandem mass spectrometric methods

EVE is a pilot project for cervical cancer screening whose aim is to test the feasibility of organized screening in the French liberal health system with a consensus of medical participants. After three and a half years, 74.8% of women aged 25 to 64 had had at least one smear. Coverage varies with age, from 89% between 25 and 29 to 56% between 55 and 60. Only 8% of smears are taken by General Practitioners. There is a tendency to space out smears because only 14% of women had had a second smear within one year and 41.1% within 2 years. On the other hand more then 20% percent of women do not return after 3 years. Pathological smears represent 1.94% of all smears. For these, a questionnaire is sent to the physician in order to get information on follow-up. This enables cytologic/histologic correlation. The histologic exam reveals a pathological lesion in 95% of cytologies consistent with invasive cancer, 91% of those consistent with high grade lesions and 70% of those consistent with low grade lesions.     

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.     

Cervical cytology screening: experience of a general hospital

At Henderson General Hospital, Hamilton, a program was introduced whereby cervical smears were taken routinely for cytologic study from all women admitted aged 17 years or older. The procedure was performed by a specially trained nurse. In a 5-year period 53% of eligible patients were screened. Of these, 32% had not had a cervical smear taken before. In 7681 smears nine instances of invasive disease were discovered: three of the cervix, three of the endometrium and three metastatic. There were 20 cases of carcinoma in situ and 2 of severe dysplasia. Evidence of infection was present in a high percentage of the smears. Hospital admission affords an excellent opportunity of applying this valuable screening procedure.     

Human papillomavirus in normal cervical smears from Cape Town

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) types in South African women with normal cervical cytology and to determine whether our results are comparable to what has been found elsewhere in the world. DESIGN: Cervical smears were collected from 262 women. SETTING: The Cape Town metropolitan area. PARTICIPANTS: A total of 262 women, aged 19-85 years. Eighty-five women attended the family planning clinic of the Gynaecology Department at Groote Schuur Hospital and 177 women consulted private gynaecological practices. MAIN OUTCOME MEASURES: The prevalence and types of HPV in 192 women with normal cervical cytology. RESULTS: The incidence of HPV DNA in cervical smears from Cape Town women with normal cytology was found to be 13% (25/192) using Southern blot hybridisation. The types of HPV found in normal cervical tissue from Cape Town did not differ significantly from those found elsewhere in the world. Nine per cent (17/192) were positive for "high-risk' HPV types which are associated with premalignant and malignant cervical lesions. In the age group 20-39 years, 15 of 92 (16%) were positive for HPV DNA, while in the age group above 39 years, 3 of 53 (6%) women were positive for HPV DNA. CONCLUSIONS: In this study, 25 of 192 (13%) women with normal cytology were positive for HPV.     

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 and prognostic relevance of malignancy-associated changes in cervical smears

OBJECTIVE: For approximately 15 years, malignancy-associated changes (MACs) have been consistently found by means of high-resolution cytometry in different tissues, especially in visually normal appearing cervical cells. Their biologic nature is not yet fully understood. The aim of this investigation was to assess the expression of MACs in cervical smears and to evaluate their prognostic relevance. STUDY DESIGN: This study was performed on normal intermediate cells obtained from 53 cytologically positive and 78 cytologically negative cervical smears. From a second sample, 31 cases showing negative cytology were selected for a prospective longitudinal study. Densitometric and texture features were generated, and MACs were described on the basis of multivariate discriminant analysis. RESULTS: Discrimination between positive and negative cases was possible, with a correct classification rate of approximately 80%. After a mean period of 29.5 months, we noted no statistically significant increase in the incidence of cervical intraepithelial neoplasia in the group of healthy but MAC-positive women as compared to those who were MAC negative. CONCLUSION: MACs were constantly expressed in the epithelium of the cervix. Although their prognostic relevance remains unclear, MACs play an important role in the effort to automate cervical cytology.     

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.     

Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears

OBJECTIVE: The study examined interrelationships between sensitivity and specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from liquid-based cervical cytologic specimens by means of receiver operator characteristics curves. STUDY DESIGN: A cohort study was performed on 265 women evaluated by colposcopy because of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion found on Papanicolaou smear. RESULTS: At a positive threshold of 0.2 pg/ml (1000 copies of human papillomavirus per test), human papillomavirus deoxyribonucleic acid testing detected 86% of women with cervical intraepithelial neoplasia and 93% of women with high-grade cervical intraepithelial neoplasia with a specificity of 30%. Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000 copies of human papillomavirus per test) improved the specificity of a positive result to 44% but decreased the clinical sensitivity to 78% for cervical intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and specificity were influenced by patient age and referral diagnosis. For example, limiting the analysis to only women with a referral for atypical squamous cells of undetermined significance found on Papanicolaou smear and a positive human papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%. CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual cellular material from liquid cytologic specimens appears to be more appropriate for older women (>30 years old) and women with atypical squamous cells of undetermined significance, as opposed to low-grade squamous intraepithelial lesion, on their Papanicolaou smears.     

Total knee arthroplasty without patellar resurfacing in active and overweight patients

Chlamydia trachomatis is a frequent sexually transmitted disease. The diagnosis of C. trachomatis infection by cytology is controversial. We compared the ability of Papanicolaou (Pap) smears to detect C. trachomatis infection with antigen detection (enzyme immunoassay; EIA) and polymerase chain reaction (PCR). One hundred sixty-seven women attending a therapeutic abortion clinic were enrolled in the study. Endocervical samples were first collected for EIA and PCR, and then Pap smears were prepared for cytologic evaluation. Eight patients were excluded from the study due to the lack of an endocervical component. The criteria established by Gupta and associates (Diagn Cytopathol 1988;4:224-229; Acta Cytol 1979;23:315-320) were used in this study to assess the specificity and sensitivity of the Pap smear in recognizing C. trachomatis infection. After EIA testing, the remaining sample was subjected to phenol-chloroform extraction to purify the DNA and then tested by PCR. Positive PCR samples were subjected to repeat phenol-chloroform and retested to confirm the positive result. Using a confirmed PCR or a blocked EIA as the extended gold standard, the incidence of C. trachomatis infection was 9.4%. Fifteen of the 159 cases reviewed were positive by extended gold standard. Thirteen (86.7%) of those 15 cases were interpreted as negative by cytology (false-negatives), and two (13.3%) cases were positive. Of the remaining 144 cases, 14 cases (9.7%) were interpreted as positive by cytology (false-positives) but were not confirmed by the extended gold standard. Ten (66.7%) of the 15 cases confirmed by the extended gold standard were interpreted as negative by EIA (false-negatives), and five (33.3%) were positive. There were no false-positives by EIA. In this study, the sensitivity and the specificity for cytology were 13.3% and 90.3%, respectively. The positive predictive value was 12.5%, and the negative predictive value for cytology was 90.9%. The sensitivity and the specificity for EIA were 33.3% and 100%, respectively. The positive predictive value was 100%, and the negative predictive value for EIA was 93.5%. Both EIA and cytology are insensitive methods compared with PCR. Based on these data, cytology should not be used to diagnose C. trachomatis infection in an asymptomatic female population with a moderate risk of C. trachomatis infection.     

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.     

Visual inspection of the uterine cervix after the application of acetic acid in the detection of cervical carcinoma and its precursors

BACKGROUND: Organized cervical cytology screening programs are not feasible in many developing countries where cervical carcinoma is an important cause of mortality among adult women. This study compared visual inspection of the cervix after application of 3-4% acetic acid (VIA, or cervicoscopy) with cytology as methods for the detection of cervical carcinoma and its precursors. METHODS: Three thousand women were examined by both VIA and cytology. Those positive on one or both of the screening tests (n = 423) or those who had clinically suspicious lesions even if the tests were negative (n = 215) were invited for colposcopy. Directed biopsies were obtained from 277 of 573 women at colposcopy. Those with moderate dysplasia or worse lesions diagnosed by histology were considered true-positives. Those with no lesions or with reactive or reparative changes at colposcopy and those for whom histology revealed no pathology, reactive or reparative changes, atypia, or mild dysplasia were considered false-positives. The detection rate of true-positive cases and the approximate specificity of the two tests were compared. RESULTS: VIA was positive in 298 women (9.8%), and cytology was positive (for atypia or worse lesions) in 307 women (10.2%). Of the 51 true-positive cases (20 cases of moderate dysplasia, 7 of severe dysplasia, 12 of carcinoma in situ, and 12 of invasive carcinoma), VIA detected 46 (90.1%) and cytology 44 (86.2%), yielding a sensitivity ratio of 1.05. VIA detected five lesions missed by cytology, and cytology detected three missed by VIA; both missed two lesions. The approximate specificities were 92.2% for VIA and 91.3% for cytology. The positive predictive value of VIA was 17.0%, and that of cytology was 17.2%. CONCLUSIONS: These results indicate that VIA and cytology had very similar performance in detecting moderate dysplasia or more severe lesions in this study. VIA merits further evaluation as a primary screening test in low-resource settings.     

The significance of endometrial cells in the cervical smear

Presence of atypical endometrial cells in a cervical smear is quite unusual; but if they are found the woman needs extra attention because of the risk of adenocarcinoma of the uterus. Postmenopausal women sometimes also have endometrial cells without atypia in the cervical smear, as a sign of endometrial pathology. We conducted a retrospective follow-up study of these women. From 1978 to 1989, 52 smears from a total of about 50,000 postmenopausal women were classified as Pap IIIA, due to the presence of normal endometrial cells. Histological follow-up was performed in 25 cases and 3 times an adenocarcinoma of the endometrium was diagnosed (6%). The smears from 142 women (pre- and postmenopausal) contained atypical endometrial cells and therefore were classified as Pap IIIA or higher. Histological follow-up was performed in 104 cases. In 48% (n = 68) an adenocarcinoma was diagnosed. In 75% of these cases (n = 51) the atypical cells were graded as severe or worse (> or = Pap IIIB). Cervical smears are not taken to detect pathology of the endometrium, but whenever atypical cells are found in the smear there is a strong indication for further (gynaecological) examination.     

Immunological identification of a basic homologue to acidic virus-inducible cucumber peroxidase

BACKGROUND: The 1991 Bethesda System for cervical/vaginal cytology reporting defined adequacy criteria for the unsatisfactory designation. Most laboratories have implemented these criteria, but clinical implications have not been established. METHODS: Researchers at two university hospitals retrieved by computer search all unsatisfactory Papanicolaou (Pap) smears taken between January 1994 and July 1995. Of 71,872 total Pap smears, 208 (0.3%) were unsatisfactory (corresponding atypical rate of 9% and a dysplasia/carcinoma rate of 6.5%). Time interval to follow-up and clinicopathologic outcome were determined. RESULTS: Approximately 26% of unsatisfactory Pap smears were from patients with a history of epithelial abnormalities. The majority (129 of 208 specimens; 62%) of follow-up Pap smears or biopsies occurred within 6 months, 5.7% within 6-12 months, and 1.4% in 12-18 months. Approximately 31% had no follow-up. The first repeat Pap smear or histologic specimen in 144 patients with follow-up was negative in 107 (74%), unsatisfactory in 6 (4%), atypical squamous cells of undetermined significance in 15 (10%), squamous intraepithelial lesion (SIL) in 13 (9%), and malignant in 3 (2%). Nonmalignant conditions contributing to the unsatisfactory smears on histologic specimens (12%) included cervicitis, endometritis, endometrial hyperplasia, and polyps. Progressive abnormalities after the first repeat specimen were noted in 7 patients (5%). A total of 23 of 144 initial unsatisfactory specimens (16% )were found to be from patients diagnosed with SIL or malignancy when all follow-up specimens were analyzed. CONCLUSIONS: The majority of patients with unsatisfactory Pap smears had follow-up studies within 6 months. A significant number (16%) of those with follow-up had eventual diagnoses of SIL or neoplasia. Benign pathologic conditions also contributed to unsatisfactory smears. This patient subset was more likely to have a history of abnormalities, confirming the importance of peer/hierarchical review of unsatisfactory smears.     

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.