A randomized control trial of two cervical spatulas

The sampling efficacy of the Ayre and Rocket cervical spatulas was compared in a randomized controlled trial involving 533 women who were attending a colposcopy clinic either for investigation of cytological abnormality or for review after treatment of CIN. Smears were compared with respect to the presence of cytological abnormality and two types of normal cervical epithelial cells (endocervical and immature metaplastic cells) which are considered indicators of adequate cytological sampling. Smears taken with the Rocket spatula were significantly less likely to contain immature metaplastic cells (95% CI on difference in proportion; 5-30%), but more likely to contain endocervical cells (95% CI 16-36%). No significant difference was found in the proportion of smears containing one or other type of indicator cell or in the yield of abnormal smears. It is concluded that the Rocket spatula offered no advantage when used in these circumstances. This study illustrates how spurious conclusions of sampling efficacy can be drawn if only one type of indicator cell is used as an endpoint.     

A randomized control trial of two cervical spatulas

Summary. The sampling efficacy of the Ayre and Rocket cervical spatulas was compared in a randomized controlled trial involving 533 women who were attending a colposcopy clinic either for investigation of cytological abnormality or for review after treatment of CIN. Smears were compared with respect to the presence of cytological abnormality and two types of normal cervical epithelial cells (endocervical and immature metaplastic cells) which are considered indicators of adequate cytological sampling. Smears taken with the Rocket spatula were significantly less likely to contain immature metaplastic cells (95% CI on difference in proportion; 5–30%), but more likely to contain endocervical cells (95% CI 16–36%). No significant difference was found in the proportion of smears containing one or other type of indicator cell or in the yield of abnormal smears. It is concluded that the Rocket spatula offered no advantage when used in these circumstances. This study illustrates how spurious conclusions of sampling efficacy can be drawn if only one type of indicator cell is used as an endpoint.     

Human papillomavirus detection for cervical cancer prevention with polymerase chain reaction in self-collected samples

OBJECTIVE: We studied the usefulness of self-sampling in cervical cancer prevention. STUDY DESIGN: A cross-sectional study was undertaken at screening services in Recife (Brazil); 253 women aged 16 to 88 years were included. Participants were randomly selected from a high-risk population for cervical neoplasia. All participants collected a self-sample with a cotton-tipped swab by rotating it against the vaginal epithelium and, possibly, the cervix. Physician-collected samples from the ectocervix and endocervix, respectively, with an Ayre's spatula and a Cytobrush endocervical brush (Medscand) were followed by thorough colposcopy. Human papillomaviruses were detected by consensus polymerase chain reaction and typed by restriction fragment length polymorphism. RESULTS: The difference among human papillomavirus results in samples that were self-collected versus physician collected was significant (P <.03). The agreements were poor among patients with cervical intraepithelial neoplasia (CIN) grade 3 (kappa <0.29) and cervical cancer (kappa < 0.10). Self-sampling missed 50% more cancers than did physician sampling (P =.04). CONCLUSION: Self-sampling with a cotton-tipped swab for human papillomavirus detection is not a safe method for the collection of samples that are aimed at primary cervical cancer screening.     

A randomized clinical trial comparing the Cytobrush and cotton swab for Papanicolaou smears.

OBJECTIVE: We sought to determine whether use of the Cytobrush/spatula or the cotton swab/spatula is better in obtaining satisfactory Papanicolaou smears as defined by the Bethesda System. METHODS: This 1-year randomized trial was performed at the Los Angeles County + University of Southern California Women's Hospital colposcopy clinic. Participants were all nonpregnant patients referred to the colposcopy clinic for abnormal Papanicolaou smears. The main outcome measurement was the effectiveness in obtaining satisfactory Papanicolaou smears as defined by the Bethesda System. Data were analyzed using the Pearson chi 2 test. RESULTS: The sampling methods had similar abilities to obtain a satisfactory smear (Cytobrush/spatula 63%, cotton swab/spatula 57%; P = .23). Less-than-optimal smears accounted for 28% of the Cytobrush group and 38% of the cotton-swab group. The Cytobrush was superior in its ability to obtain endocervical cells (Cytobrush 80%, cotton swab 60%; P less than .01). Both sampling methods had similar rates of correlation with histologic diagnosis. No complications were associated with either technique. CONCLUSIONS: The Cytobrush/spatula is superior to the cotton swab/spatula in obtaining endocervical cells. There appears to be no difference in each method's ability to obtain satisfactory smears. Application of the Bethesda System results in a significant number of less-than-optimal smears using either technique.     

Conservative management of the abnormal smear during pregnancy. A long-term follow-up

One hundred and thirty-two pregnant women who had a smear suggestive of cervical intra-epithelial neoplasia (CIN) II or more during the 10th to 12th gestational week, were followed with repeated smears and colposcopy every month and, when indicated, a colposcopically guided biopsy. Post-partum follow-up included cytology, colposcopy, portio biopsies and endocervical curettage. Seventy-nine women with normal findings post partum were checked once a year in a long-term study. A close correlation (71% of CINIII) was found between cytological and histological diagnoses in cases of persistent (three or more) abnormal smears. However, in women with regression of the cytological diagnosis, high frequencies of histologically verified CIN were found. Thus, 37.5% (18/48) of normal or CINI smears were histologically still CINIII. Histologically verified CIN during pregnancy, on the other hand, showed a post partum progression of two degrees or more of CIN in only two cases. Cytology seemed to be inappropriate post partum, with 23.3% smears which were normal or suggestive of CINI, when histology showed CINIII. In a long-term follow-up, 24% of women with a normal post partum follow-up for at least one year had a subsequent recurrence of CIN. It is concluded that follow-up of abnormal smears during pregnancy with repeated smears is not a reliable method. Post-partum follow-up should include at least colposcopy and a biopsy when indicated by the colposcopical examination. Women with a normal post partum follow-up constitute a high risk group for future recurrence of CIN and should be carefully followed for at least 5 years.     

Comparison of cervical smears secured with different instruments

BACKGROUND: In this presentation we have compared the results from cytologic samples obtained with the cervical brush and Ayre's wooden spatula, against samples obtained with Acellon Combi. METHODS: One thousand cervical smears were collected. This was a cross-sectional study, where it was decided randomly to use cervical brush for sampling of the endocervix and Ayre's wooden spatula for exocervix or Acellon Combi for both. RESULTS: The combination of the cervical brush and the wooden spatula yielded an acceptable quantity of columnar cells in 71.6% of the cases, during both endocervical and exocervical sampling, while the Acellon Combi yielded an acceptable quantity in 61.7% of the cases (p<0.01). The combination of brush/spatula yielded an acceptable quantity of squamous cells from samples of endocervix and exocervix in 87.5% cases, while with the Acellon device amounted to 77.4% (p<0.001). Highly significant differences in the state of cellular preservation of samples from endocervix obtained with cervical brush technique were found upon comparison to Acellon group. CONCLUSIONS: Henceforth, we believe that the use of the cervical brush and the Ayre wooden spatula increases the quantity and preservation of the cells retrieved during cervical smears compared to Acellon Combi.     

Should the Cytobrush be used in routine screening for cervical pathology?

In 632 women visiting a family planning clinic, paired cervical smears were taken using a wooden spatula and a Cytobrush. Of the spatula smears 7.8% were unreliable with too little or scanty material to allow a cytologic diagnosis (class 0); 17.7% of spatula smears were inadequate, lacking endocervical cells. Combined spatula/Cytobrush cytology reduced these figures significantly; 4.3% unreliable smears and 3.2% inadequate specimens. Seventy-three (11.6%) of the smears revealed some abnormality, in most cases Papanicolaou class IIIA, suggestive of mild dysplasia. In 10 cases, dysplastic cells were found only in the Cytobrush cytology. It is concluded that the Cytobrush adds to the improvement of smear quality and the accuracy of routine cervical cytology obtained by relatively inexperienced smear takers.     

Evaluation of colposcopy in the postmenopausal woman

Summary. Cytology, colposcopy and histology findings in 121 postmenopausal and 120 premenopausal women referred to the Oxford colposcopy clinic were compared; 88% of postmenopausal and 69% of premenopausal women were referred by their general practitioners. Cervical smear reports, within the preceding 5 years, were available for 21% of the postmenopausal and 54% of the premenopausal women. Colposcopic assessment was technically unsatisfactory in 53% of the postmenopausal women because the transformation zone was not completely visible, this contributed to a cone biopsy rate of 71% in this group. Only 17% of postmenopausal women with cervical intraepithelial neoplasia (CIN) were managed with local ablative techniques compared with their use in 61% premenopausal patients overall and in over 70% of the women under 35 years. Local ablation was used in 10 of 14 women using hormone replacement therapy. The cytological false negative rate for postmenopausal Papanicolaou class III, IV and V smears was 9% but for persistent class II inflammatory smears it was 43%. Nine of 23 postmenopausal women with persistent inflammatory dyskariosis despite antibiotic or antifungal treatment were found to have colposcopic appearances of CIN and four had microinvasion or invasion. Colposcopy revealed probable microinvasive or invasive disease in 17 postmenopausal women, seven of whom had class II or III cytology.     

Evaluation of colposcopy in the postmenopausal woman

Cytology, colposcopy and histology findings in 121 postmenopausal and 120 premenopausal women referred to the Oxford colposcopy clinic were compared; 88% of postmenopausal and 69% of premenopausal women were referred by their general practitioners. Cervical smear reports, within the preceding 5 years, were available for 21% of the postmenopausal and 54% of the premenopausal women. Colposcopic assessment was technically unsatisfactory in 53% of the postmenopausal women because the transformation zone was not completely visible, this contributed to a cone biopsy rate of 71% in this group. Only 17% of postmenopausal women with cervical intraepithelial neoplasia (CIN) were managed with local ablative techniques compared with their use in 61% premenopausal patients overall and in over 70% of the women under 35 years. Local ablation was used in 10 of 14 women using hormone replacement therapy. The cytological false negative rate for postmenopausal Papanicolaou class III, IV and V smears was 9% but for persistent class II inflammatory smears it was 43%. Nine of 23 postmenopausal women with persistent inflammatory dyskariosis despite antibiotic or antifungal treatment were found to have colposcopic appearances of CIN and four had microinvasion or invasion. Colposcopy revealed probable microinvasive or invasive disease in 17 postmenopausal women, seven of whom had class II or III cytology.     

Cervex-Brush and Cytobrush. Comparison of their ability to sample abnormal cells for cervical smears

A study was designed to test specimen adequacy and the detection of disease using two new cervical cytologic sampling devices, the Cervex-Brush and Cytobrush plus a modified Ayre spatula. Two clinicians used each device at random. The laboratory was blind to the sampling method, and the results were compared with those from control samples (Ayre spatula with cotton swab or alone). The 567 test samples were compared with 569 age-matched control samples. The Cervex-Brush and Cytobrush plus spatula were comparable in detecting disease, and both were improvements over the control method. Both the Cervex-Brush and Cytobrush plus spatula produced more consistent good smear quality across the age range studied than did the control method, which resulted in a lower percentage of good-quality smears in older women. Use of the Cytobrush plus spatula and the control method produced smear results the quality of which varied considerably with each clinician.     

Performance of the Cytobrush in patients at risk for cervical pathology: does it add anything to the wooden spatula?

In 130 high-risk patients for cervical pathology paired smears were obtained with a wooden spatula and a Cytobrush. The Cytobrush was useful in lowering the amount of inadequate smears (2 vs 22%, p less than or equal to 0.01), and detected more abnormal cytology in combination with the spatula compared to the spatula smear alone (27 vs 35%, p less than or equal to 0.05). In 6 cases, adequate false-negative spatula smears, containing endocervical cells, were corrected by the Cytobrush. It is concluded that the Cytobrush is useful in lowering the amount of inadequate smears and false-negative cytology, while there is little evidence of false-positive cytology. The use of the wooden spatula/Cytobrush-combination is recommended in high risk populations.     

Human papillomavirus (HPV) in an Icelandic population: correlation of HPV DNA to cyto- and histopathologic lesions and evaluation of treatment strategies

This study is based on 100 cases with cervical intra-epithelial neoplasia (CIN) smears referred for colposcopy and 200 controls with normal smears. The study analyses (a) the frequency of different grades of CIN and koilocytotic lesions among the cases based on cyto- and histopathologic findings; (b) the frequency of human papillomavirus (HPV) among the cases with Virapap/Viratype (V/V) in biopsies vs swabs and among the controls with V/V and polymerase chain reaction (PCR) in swabs; (c) the frequency of the HPV types according to the grade of CIN. Among the cases koilocytotic lesions were found in 98% of the biopsies and 27% of the smears. High-graded smears and high-risk viruses had at entry a positive predictive value (PPV) of 80% and 88% respectively and a sensitivity of 72% for histologically verified high-graded CIN lesions. Both tests combined increased the sensitivity to 88%. The false-negative rate of colposcopy was 3% and the undergraded rate of CIN I and unclassified CIN smears for histologically verified CIN II–III was 62%. Among the cases the rate of HPV positive tests increased with a higher CIN grade. Cytology and colposcopy are complementary for the diagnosis of CIN and the swabs and biopsies for the diagnosis of HPV. Among the cases the rate of HPV-positive tests with V/V was 62% (97% high-risk viruses) and among the controls 5.5% (78% high-risk viruses). Among the controls the frequency of HPV occurrence with PCR was 11.2% and decreased with older age. The therapeutic conclusions are that the high-graded CIN lesions should receive ablative treatment irrespective of HPV typing, whereas low-graded lesions with high-risk viruses should be treated or observed closely.     

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.     

Performance of Pap smear and human papilloma virus testing in the follow-up of women with cervical intraepithelial neoplasia grade 1 managed conservatively

BACKGROUND: Conservative management (follow-up) of cervical intraepithelial neoplasia grade 1 (CIN1) is acceptable, but evidence on performance of follow-up tools, such as Pap smear and human papilloma virus (HPV) test, is still needed. METHODS: A cohort of 78 women with histologically confirmed CIN1, referred because of atypical squamous cell or low-grade squamous intraepithelial lesion in their Pap smear, was enrolled between August 2000 and September 2002 and was prospectively followed-up at 6 and 12 months, until September 2003. Follow-up examinations included Pap test and Hybrid Capture II (HCII) with high-risk HPV, colposcopy, and cervical biopsies in patients with persistent abnormalities. Odds ratios and performance indicators (with 95% confidence interval) were calculated for HPV and Pap test results in detecting biopsy-confirmed CIN during the follow-up. RESULTS: Thirty-seven (47%) of the women were HPV-positive at baseline. At first follow-up visit, 30 women had persistent CIN1 and one woman progressed to CIN2; 15 patients had CIN1 and one patient CIN2 at the second follow-up visit. Women with persistent CIN1 (or progression) during follow-up had a significantly higher HPV detection rate and abnormal Pap tests, compared to women with regressive disease. Cytology had a far better sensitivity in detecting CIN than HCII at the first follow-up visit (81 versus 52%, respectively), whereas both examinations had equivalent sensitivities at the second follow-up visit (69 and 56%, respectively). Cytology had a superior negative predictive value at the first follow-up visit and better positive predictive value, in addition, at the second visit. CONCLUSIONS: Because cytological abnormalities correlated generally better with the persistence of biopsy-confirmed CIN1 in this follow-up protocol, HCII test is the second-hand option to Pap test, but the use of both Pap and HCII together seems an unnecessary waste of resources.     

Diagnosis of cervical intraepithelial neoplasia and human papillomavirus infection: punch biopsy versus cervical smear

Summary In 102 patients referred to our colposcopy clinic because of one to three Papanicolaou smears indicating cervical intraepithelial neoplasia (CIN) and/or abnormal colposcopy, routine smears and colposcopically directed punch biopsies were taken simultaneously. For detection and typing of human papillomavirus (HPV)-DNA in situ hybridization was performed in all biopsies and in 46 of the cervical smears. In cases of dysplastic lesions the number of HPV 16/18 (40.5%) and 31/33 (42.9%) was markedly higher than HPV 6/11 (16.6%) infection rate. In cases where simultaneous in situ hybridization in biopsy specimen and cervical smears was performed 21.7% showed a HPV negative smear and a positive biopsy, in 6.5% the results were the other way round. In 34.9% of cases with CIN I and 9.5% of cases with CIN II verified by punch biopsy the cytological smear did not indicate dysplasia. Our data show that mild and moderate CIN lesions of the cervix as well as HPV infection are detected more frequently by a combination of cervical smear and colposcopically directed punch biopsy than by cervical smear alone.     

A Randomized Comparison of the 3 Papanicolaou Smear Collection Methods

Summary: 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 × 10^-6, p=4.49 × 10^-7 respectively). There was no statistically significant difference between the Cytobrush-spatula and Cervex brush groups (p=0.0779). We concluded that the Cytobrush-Ayre spatula and the Cervex brush sampling methods were equally effective in obtaining endocervical cells in Papanicolaou smears.     

传统宫颈细胞学检查与薄层细胞学检测的分析比较与评价

目的　对子宫颈癌和癌前病变的检查方法进行综合分析比较与评价。方法　对 2 10 0例患者分别采用传统宫颈细胞涂片 (10 4 9例 )和新柏氏薄层细胞学检测系统 (Thinprepcytologictest,TCT 10 5 1例 )进行宫颈病变的早期筛查 ,对 2 0 6例细胞学阳性或临床可疑的患者行阴道镜下活组织检查。结果　TCT标本的不满意率(0 .4 8% )明显低于传统宫颈细胞涂片 (1 4 3% ) ,明显提高了子宫颈癌及癌前病变的阳性诊断率 ,降低了对AS CUS的诊断率。传统细胞学和TCT检查与阴道镜下活检病理结果符合率分别为LSIL :5 6 82 % (2 5 4 4 )和 74 36 %(2 9 39) ,HIS :4 5 4 5 % (5 11)和 85 71% (18 2 1) ,HPV感染的符合率分别为 5 3 5 7% (15 2 8)和 75 6 8% (2 8 37)。HPV感染和CIN的高发年龄分别为 2 0～ 30岁和 30～ 5 0岁。结论　宫颈细胞学筛查是子宫颈癌及癌前病变早期诊断的重要手段 ,TCT独特的取材与制片方法 ,更有利于宫颈阳性病变的检出 ;细胞学筛查异常或临床可疑的患者 ,应在阴道镜下多点活检 ;细胞学提示HPV感染者 ,应行病理和HPV -DNA检测证实。     

Laser conization: follow-up in patients with cervical intraepithelial neoplasia in the cone margin

Combination laser conization was performed in 469 patients for the treatment of cervical intraepithelial neoplasia (CIN). In 58 cases (12.4%), CIN was located in the margins of the cone. Fifty-one patients with involvement of the margins were evaluated by cytologic examination, using the Ayre spatula and the Cytobrush, and by cervical biopsy and endocervical curettage (ECC). In six cases, the histologic evaluation was positive, and in three of these cases, the cytology was positive too. Hysterectomy was performed in five cases, but in only one case was a significant lesion demonstrated in the uterus. These results justify expectant, conservative management of patients treated with combination laser conization. Follow-up based on colposcopy and cytology seems sufficient.     

Detection of abnormal cervical smears. A comparative study

The inefficiency of the Ayres Spatula in detecting abnormality in cervical cytology has been demonstrated recently in a number of trials. In a randomized single-blind trial we have compared the Multispatula with the Ayres Spatula in a group of 158 women who previously had abnormal smears and had been referred to colposcopy clinics in the Lewisham and North Southwark Health Authority of London. The quality of the smears, as assessed by the presence or absence of endocervical cells, revealed that the Multispatula (87.3% pick-up) produced significantly better smears (p less than 0.005) compared with the Ayres Spatula (54.4% pick-up). In 149 smears collected with the Multispatula, atypia was confirmed. However, in only 129 smears taken with the Ayres Spatula were abnormal smears detected (p decreases less than 0.005). We concluded that the Multispatula produces a better quality smear which results in a decreased false negative rate in comparison with the Ayres Spatula.     

The Multispatula; a spatula adjustable to the shape of the individual cervix

The Multispatula, which is adjustable to the specific shape of each individual cervix, was compared with the Ayre spatula in 236 patients. Two smears were taken from each woman, one with the Ayre and one with the Multispatula. The Multispatula had a significantly higher percentage of smears containing endocervical cells than the Ayre spatula. Disadvantages of the Multispatula are its high price and the sharp edges causing somewhat more pain and bleeding. There were major differences in the quality of the smears between the various sample takers.