Cost analysis of PAPNET-assisted vs. conventional Pap smear evaluation in primary screening of cervical smears

OBJECTIVE: To assess the difference in costs between PAPNET-assisted and conventional microscopy of cervical smears when used as a primary screening tool. STUDY DESIGN: We performed time measurements of the initial screening of smears by four cytotechnologists in one laboratory. Time was measured in 816 conventionally screened smears and in 614 smears with PAPNET-assisted screening. Data were collected on the components of initial screening, clerical activities and other activities in the total work time of cytotechnologists in the routine situation and on resource requirements for both techniques. RESULTS: PAPNET saved an average of 22% on initial screening time per smear. Due to costs of processing and additional equipment, the costs of PAPNET-assisted screening were estimated to be $2.85 (and at least $1.79) higher per smear than conventional microscopy. The difference in costs is sensitive to the rate of time saving, the possibility of saving on quality control procedures and the component of the initial screening time in the total work time of cytotechnologists. CONCLUSION: Although PAPNET is time saving as compared with conventional microscopy, the associated reduction in personnel costs is outweighed by the costs of scanning the slides and additional equipment. This conclusion holds under a variety of assumptions. Using PAPNET instead of conventional microscopy as a primary screening tool will make cervical cancer screening less cost-effective unless the costs of PAPNET are considerably reduced and its sensitivity and/or specificity are considerably improved.     

The use of the PAPNET automated cytological screening system for the diagnosis of oral squamous carcinoma

levine t. s., njemenze v., cowpe j. g. and coleman d. v. (1998) Cytopathology 9, 398–405
The use of the PAPNET automated cytological screening system for the diagnosis of oral squamous carcinoma
The automated PAPNET screening system has been developed to recognize abnormal cells in cervical smears. Given that the oral mucosa sheds cells resembling superficial and intermediate cells of the cervix, the aim of this study was to assess whether the PAPNET system could be used to detect dysplastic cells in oral mucosal smears. Sixty-two oral smears from 27 patients were examined by both light microscopy and using the PAPNET system from clinically abnormal and normal areas by two pathologists. The clinically abnormal sites were also biopsied for histological analysis. There was 100% correlation between the manual and PAPNET screening results. Cytological interpretation of oral smears by both manual and PAPNET screening methods correctly diagnosed squamous cell carcinoma in 14/23 (61%) of patients who had all been confirmed by biopsy. The nine patients with false-negative cases could be attributed to poor smear technique and preparation. The PAPNET system can be used to identify abnormal cells in oral smears and, as such, may have an application for screening those populations at high risk of oral cancer—provided that adequate tuition is given in smear technique.     

Quality control of cervical cytology in high-risk women. PAPNET system compared with manual rescreening

OBJECTIVE: To compare the effectiveness of the PAPNET System with conventional rescreening of negative cervical smears in a high-risk population. STUDY DESIGN: Three thousand ninety-seven negative cervical smears from women with past history of cervical abnormalities were rescreened manually and with the PAPNET System. There were two reviews of PAPNET images: the first by two cytotechnologists with limited exposure to the instrument, and the second, limited to smears with discrepant diagnoses, by an expert in the use of the system. The remaining discrepant smears were submitted to a blinded microscopic review by a third party. The a priori consensus diagnosis was arbitrarily established when the result of two of the three reviews--manual, PAPNET and the independent third review--were concordant. The results of rescreening were compared with available biopsies. RESULTS: On manual rescreening of the 3,097 smears, 2,901 (93.66%) were reported as negative and 170 (5.49%) as abnormal. On the first PAPNET review, 2,938 (94.87%) were reported as negative and 150 (4.84%) as abnormal. There were 144 smears with discrepant diagnoses. After the second PAPNET review of these discrepant smears, the agreement between manual and PAPNET rescreening rose from 94.27% to 95.58%. A final, blinded review of 89 residual discrepant smears was used to establish consensus diagnoses. The diagnoses made by PAPNET-assisted rescreening agreed much better with the consensus diagnoses than did manual rescreening (Kappa = .61 vs. Kappa = -.32, P < .001). When compared with the results of 50 available biopsies, PAPNET-assisted rescreening also had a somewhat lower false negative rate (sensitivity 58.82% vs. 41.18%, P = .17) and a statistically significant lower false positive rate (specificity 63.64% vs. 36.36%, P = .01). CONCLUSION: PAPNET-assisted rescreening, when carried out by an experienced person, is more efficient than manual rescreening.     

Potentially difficult smears of women with squamous cell carcinoma pose fewer problems when PAPNET is used for primary screening

The diagnosis of squamous cell carcinoma (SCC) on a cervical smear is often far from easy. This study reports the analysis of 40 true-positive SCC smears detected in primary PAPNET screening and eight false-negative (FN) conventionally screened smears. All FN cases contained sparse abnormal material (< 10% of the slide). In these potentially difficult cases the diagnosis on the PAPNET images was not hard. Statistical analysis of the quantitative data indicated that the PAPNET images of the FN cases and the true-positive cases differed in some aspects. PAPNET highlighted the importance of background information (old blood, fibrin and necrosis). In addition, all FN smears contained cancer cells in the PAPNET images, allowing a correct diagnosis.     

Prospective study of PAPNET: review of 25656 Pap smears negative on manual screening and rapid rescreening

In this prospective study, 27,014 Pap smears were selected for PAPNET review on the request of the referring practitioner or patient. Smears that were negative on routine manual screening were submitted for rapid rescreening. Smears considered normal after these two manual screens (n = 25,656) were reviewed using the PAPNET testing system. Routine manual screening identified 1340 (4.96%) of the smears as abnormal, and a further 18 (0.07%) abnormalities were detected by rapid rescreening. PAPNET review identified an additional 102 (0.4%) abnormal smears, including 10 histologically confirmed high grade lesions. The use of PAPNET testing following routine manual screening and rapid rescreening in tandem, enables cytologists to detect additional diagnostically significant abnormalities and reduce the rate of false-negative smears.     

Evaluation of PAPNET-assisted cervical rescreening

Evaluation of PAPNET-assisted cervical rescreening
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.     

Reproducibility in double scanning of cervical smears with the PAPNET system

OBJECTIVE: To determine the reproducibility of the PAPNET scanning station (Neuromedical Systems, Inc., Suffern, New York, U.S.A.) in selecting cells from a cervical smear. STUDY DESIGN: We compared the images of 196 smears that were scanned on two occasions by the PAPNET scanning station on two monitors simultaneously and compared the cellular contents and technical records provided by the scanning station. The sample consisted of 62 positive smears (mild dysplasia and more) and 134 negative smears. RESULTS: Although differences were found in the technical information provided by the scanning station (kappa = .65, 95% confidence interval [CI] = .51-0.79) and in the reported percentages of air bubbles (kappa = .60, 95% CI = .51-.68), the detection of abnormal cases was not affected. Furthermore, the agreement on microscopic review was excellent (kappa = .92, 95% CI = .88-.96). In nine cases that did not differ in tech code or percentage of air bubbles, however, differences were found in the cellular content of the tiles that would have led to different advice for additional microscopic review. This would have had important clinical consequences in two cases because a serious abnormality would have been missed. CONCLUSION: The consistency of the PAPNET scanning system is somewhat on the low side in providing technical information, although this did not affect the clinical outcome. In nine cases, for example, we found differences in the demonstration of cells in the tiles on the screen; two would have had clinical consequences. It is important to set goals for the performance of the machine and to incorporate them in the procedures to be used as standard practice. This is especially true when the scanning stations are going to be operated on site in the cytology laboratory.     

Analysis of lifestyle data and cytologic findings in a pilot cervical screening project in rural Vietnam.

OBJECTIVE: To evaluate the possibilities of a cervical cytology screening program and the importance of lifestyle parameters in women living in rural Vietnam. STUDY DESIGN: Screening took place in Quangninh province in the north of Vietnam. From 700 women screened for the first time, smears were prepared and read by a cytotechnologist. The number of children and abortions (some women having had 10 abortions) allowed us to study the relationship of these life-style parameters with disturbed vaginal ecology (defined as the presence of Candida, trichomonads or cocci in the smear). RESULTS: The smears from farmers showed the greatest ecologic disturbances in vaginal flora. Water supply turned out to be important for coccoid overgrowth. Scores for both fungal infection and coccoid overgrowth were related to profession. Candidosis proved to be very prominent in cytologically negative smears: the organisms were found (often in abundance) in 95 of 661 negative smears but were absent from cytologically positive smears. CONCLUSION: Since only two cases of CIN 3 were found and no cases of invasive carcinoma, cervical screening for cancer ought not to be the first priority for rural Vietnam.     

Cost effectiveness of population screening and rescreening for cervical cancer in the Netherlands

In a screening program for cervical cancer held in the western part of the Netherlands in 1978, it was shown that the incidence of positive cases dropped from 8.0% to 1.4% when repeat screening was performed within two years; however, the incidence of mild dysplasia remained the same (13.0%). Forty percent of the allocated funds were used for canvassing. Recanvassing of the no-response group did not result in the finding of positive cases. Of the ten positive cases in the rescreened group, four had had inadequate negative smears previously, and two had had adequate negative smears; in two cases the previous smears were reclassified as dysplasias, and in the two remaining cases endocervical carcinoma cells were found in the additional endocervical smear. In light of the high canvassing costs of population screening and the low detection rate of positive cases in the rescreened group, as described in this paper, it appears overly costly to repeat population screening with two years.     

Feasibility of cytology-based cervical cancer screening in rural Cameroon

OBJECTIVE: To determine the prevalence of cervical cancer and its precursors in a rural population in Cameroon and to evaluate the feasibility of a cytology-based screening program in such areas. STUDY DESIGN: A prospective study was conducted in the rural town of Bafang. Following an advocacy campaign, 750 women were recruited. After a clinical examination, all women had a Pap smear with the Cervex Brush. Each sample had two preparations, conventional and liquid based. The conventional smears were interpreted in Bafang. Cytologically abnormal cases, those with clinical inflammation and/or macroscopic cervical lesions, had a colposcopic examination and directed biopsy. HSIL and colposcopically abnormal cases were treated with large loop excision of the transformation zone (LLETZ). The liquid-based preparations and histopathology were performed in Geneva and the results sent to Cameroon for patient follow-up. RESULTS: Mean age and parity of the women screened were 43.7 years and 7.8, respectively. The conventional smears showed 3.6% cervical abnormalities: 2% (15/740) ASCUS/LSIL and 1.6% (12/740) HSIL. The liquid-based preparations showed 12.6% (91/722) cervical abnormalities: 10.1% (73/722) ASCUS/LSIL and 2.5% (18/722) HSIL. Fifty percent of samples in both preparations showed evidence of inflammation. Histology was performed on 64 colposcopically directed punch biopsies and LLETZ specimens. The histologic diagnoses agreed with the cytologic findings in 60% (14/23) of conventional smears and 85% (12/14) of liquid-based preparations. CONCLUSION: There is a high rate of cervical intraepithelial neoplasia in the unscreened rural population of Cameroon. The situation is complicated by a high rate of cervical infection. A population-based cytologic screening program for cervical cancer would not be feasible in rural Cameroon because of high cost, low quality and limited technical facilities. Rural Africa requires an algorithm using a simple, low-cost technique of mass screening and an improved cytology service only to triage selected patients.     

A study of the effect of introducing a restrictive cervical screening policy on laboratory workload and cervical cancer detection rates

This study examines the effect of a change in screening policy on the detection rate of severe dyskaryosis. During 1987 a total of 423 cases of severe dyskaryosis were identified by the Avon Screening Programme. Eleven per cent of these abnormal smears were repeat smears taken without clinical indication within the recommended 5 year recall period (interval smears). In a comparable control group of negative smears 31% were interval smears. Twenty-five per cent of the dyskaryotic interval smears (3% of the total severely dyskaryotic smears) were taken within 3 years of the previous negative smear, compared with 50% of the control group. By discouraging opportunistic smears within 5 years of the previous smear, the laboratory workload could be reduced by 30%, or within 3 years of the previous smear by 15%. There is, however, a risk of 11% and 3% respectively of missing a significant lesion (severe dyskaryosis).     

Rapid pre-screening of cervical smears as a method of internal quality control in a cervical screening programme

Objective:  To evaluate the performance of rapid pre-screening (RPS) as a method of internal quality control in the cytopathological examination of cervical smears for cervical cancer screening.
Methods:  The sample consisted of 6135 cervical smears submitted to RPS and routine screening (RS) methods. The smears classified as negative in RPS and RS were considered final diagnoses, and were not, therefore, submitted to any additional review. The smears identified as suspect or unsatisfactory according to RPS were analysed separately by two different cytologists irrespective of the diagnosis reached in RS. Smears considered abnormal or unsatisfactory at RS were also reviewed. When both cytologists issued concordant diagnoses, this was considered the final diagnosis. Discordant results were analysed by a third cytologist and a consensus meeting was held to define the final diagnosis.
Results:  Taking abnormalities detected by RS as the denominator, RPS had a sensitivity of 63.0% for the detection of all abnormal smears and 96.7% for high grade squamous intraepithelial lesion (HSIL). When compared with the final diagnosis, sensitivity of RPS for all abnormal smears was 74.9% and for HSIL 95.0%. Of the 529 abnormal smears confirmed in the final diagnosis, 2.15% were detected only by the RPS.
Conclusion:  RPS is an effective alternative method of internal quality control with high sensitivity for the detection of more severe lesions. It also permits monitoring of the laboratory rate of false-negative results, and allows constant evaluation of the performance both of the pre-screening and RS cytologists.     

An assessment of partial rescreening as an internal quality control method for cervical smears

Partial screening was performed on 10 800 cervical smears, comprising 8640 filed negative and unsatisfactory smears and 2160 newly received smears prior to conventional screening. Each slide was screened for 30 s and those considered abnormal were reviewed by standard screening. Partial screening led to the detection of 27 additional infections and 44 additional cytological abnormalities. These detection rates are better than those obtained with the traditional method of rescreening only a proportion of smears. Amongst the smears partially screened before conventional screening, partial screening detected 37-66% of infections and 22-71% of cytological abnormalities. We recommend the use of partial rescreening of all negatively reported smears as a method of internal quality control in cervical cytology laboratories.     

Optimized quality of histologic images allows the use of neural network scanning in diagnosis of fungal infection of abnormal nails

OBJECTIVE: The neural network scanning (NNS) system, formerly known as Papnet, is capable of selecting fungi in cervical smears. The objective of this study was to investigate whether the optimized quality of histologic images created using a combination of coagulant fixation and microwave histoprocessing allows the application of this computer-assisted microscopy in the diagnostic process. STUDY DESIGN: In a prospective study, 117 abnormal nails clinically suspect for fungal disease werefixed in a coagulant fixative, BoonFix, processed in a microwave histoprocessor to obtain optimal paraffin sections and stained with the periodic acid-Schiff (PAS) method. The stained paraffin sections were randomly numbered and screened by two independent pathologists for diagnosis of fungal hyphae and spores. The same sections were subsequently scanned by a neural network, and a maximum of 128 digital images produced by the system were screened and diagnosed by pathologists. Using light microscopy as the gold standard for diagnosis of fungi, the usefulness of NNS was then assessed. RESULTS: The fungi and spores were clearly demonstrated in the paraffin sections, and the NNS system detected and recorded them efficiently. The hyphae and spores could be identified in these pixilated images with relative ease. Of the 117 examined cases, 50 were positive and 47 negative by both methods. In the 20 remaining cases, NNS did not present images of fungi that were present in the histologic sections. In practice, this implies that only 67 out of 117 cases (57%) must be screened by light microscopy. NNS recorded not only fungi and spores in the 128 digital images but also artifacts, such as round, deeply PAS-positive granules of talcum powder, which by light microscopy might be mistaken for fungal spores. CONCLUSION: NNS proves applicable for the selection of spores and fungi if the histologic sections are of sufficiently high quality. As a result, the number of slides to be screened by light microscopy can be reduced substantially. In a throughput diagnostic laboratory handling a large number of such cases this technology can be highly valuable.     

Cervical cytology screening history of women diagnosed with adenocarcinoma in situ of the cervix: a case-control study

OBJECTIVE: To determine whether women diagnosed with adenocarcinoma in situ (AIS) of the cervix are as well screened as healthy control women. STUDY DESIGN: A case-control study was performed (307 cases, 1,228 controls) within a statewide registry. Cases consisted of women diagnosed with AIS on histology between 1995 and 2001. Screening histories were compiled from registry records. Variables of interest included number of previous negative Pap smears, time interval since last negative Pap smear, median time between previous negative Pap smears, proportion of negative Pap smears with an endocervical component and history of cervical abnormality. RESULTS: Conditional logistic regression showed that cases and controls did not differ significantly in the number of previous negative smears or in the median time between previous negative smears. Decreasing time since last negative smear was protective against AIS, with controls more likely to have had a recent negative smear. There was no difference in the proportion of previous negative smears with an endocervical component between cases and controls; however, some complex temporal relationships were observed in the regression analysis. CONCLUSION: Women who are diagnosed with AIS have a screening history similar to that of healthy, control women. The findings are consistent with the concept that AIS is predominantly a screening-detected disease.     

The Irrigation Smear—A New Cytodiagnostic Technique for the Detection of Cancer of the Uterine Cervix

Using the Davis cytopipette, cytologic smears were prepared from 2014 patients; 1367 of these specimens were obtained by the patients themselves. The series included 57 cases of carcinoma or atypia of the cervix, and 50 (88%) of these cases were found to have abnormal cells in the irrigation smear.Cytopipette samples were obtained by a nurse from 647 Eskimos, but cell preservation in this group was not satisfactory because of a delay of several weeks in preparing the smears. Accurate results depend also on specific training of the personnel reading the smears because fewer cells may be present in these smears than in cervical scrape smears.The irrigation smear is recommended as a reasonably accurate method of screening women for cancer of the cervix if they are not being examined regularly by the cervical scrape method. Hospital admissions of females may be a fruitful source of such cases.     

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.     

Performance of monolayered cervical smears in a gynecology outpatient setting in Kuwait

OBJECTIVE: To compare ThinPrep (TP) Papanicolaou smears (Cytyc Corp., Box-borough, Massachusetts, U.S.A.) with matching conventional Papanicolaou (CP) smears for specimen adequacy, cytologic quality, diagnostic accuracy and screening time. STUDY DESIGN: In this prospective study of 1,024 women a split-sample, matched-pair design in favor of CP slides based on single-blind criteria was followed with a smear on a glass slide for CP and the remaining material collected in Preserv-Cyt solution (Cytyc) for a TP smear. A Cytobrush (Medscand, Hollywood, Florida, U.S.A.) was used for smear preparation for CP. TP smears were processed in ThinPrep 2000 (Cytyc). Smears were stained with Papanicolaou stain and were interpreted according to the Bethesda system. RESULTS: The number of satisfactory but limited (SBL) cases with TP were 77 (7.5%) as compared to 127 (12.4%) with the CP method. This reduction in SBL smears with the TP method and consequent increase in satisfactory smears were highly significant (P < .001) by McNemar's test. As regards unsatisfactory smears in discordant pairs, although the number of unsatisfactory smears was higher with TP (41 cases) as against CP (27 cases), the difference was not statistically significant (P < .05). The split-sample method showed a high correlation between the CP and TP diagnoses. TP smears had a significant advantage over CP smears in the reduction in the number of ASCUS and AGUS cases (14 vs. 29) (P < .05) and increased the pickup rate of LSIL, 6 vs. 1. Time taken to screen the TP smears was half that of CP smears. No cases of LSIL or HSIL were missed on TP smears. CONCLUSION: The liquid-based processor significantly improved the adequacy and quality of smears, resulting in fewer recall cases for SBL smears, leading to more definitive diagnoses in atypical cases, increasing the pickup rate of LSILs and reducing the screening time. A machine handling multiple specimens automatically would decrease cost and be an asset to a cytopathology laboratory.     

Exploring avenues for best use of cytotechnologists in non‐gynaecological cytology: Double screening or independent sign‐out

Objective

Cytotechnologist (CT) screening workload has been decreasing due to the falling number of Papanicolaou tests. This continuing trend has prompted exploration of ways to best employ the CT skillset. One potential way of more effective use is by having two CTs double screen non‐gynaecological (NGC) cases to assess whether this improves screening quality and concordance with pathologists. Another is evaluating the CT's performance on low‐complexity negative NGC cases for a potential independent CT sign‐out without pathologist review.

Methods

In total, 1119 NGC cases were reviewed; 577 screened by two CTs and 542 screened by one CT. All cases were signed out by a pathologist and all CT interpretations were compared to the pathologist final diagnoses. The disagreements were classified based on degree of discrepancy. The extra workload by adding the second screener was assessed.

Results

The agreement rate between the CT's screening interpretation and pathologist's interpretation did not improve by adding a second CT compared to a single screener (91.5% vs 92.9%, respectively). CT to pathologist concordance was very high on low complexity NGC cases (voided urine, fluid, sputum) whether screened and interpreted as negative by one CT (97.3%) or two CTs (99.3%).

Conclusion

Double screening of NGC cases by two cytotechnologists prior to pathologist sign‐out does not improve screening quality and is not cost‐effective. The high concordance between the CTs and pathologists in this limited group of low complexity negative cases suggests that such cases could be signed out independently by cytotechnologists.     

Quality assurance in cervical cancer screening

Objectives. to examine the effectiveness of introducing External Quality Assessment (EQA) into all laboratories which undertake gynaecological cytopathology. to assess pathologists and cytotechnologists regularly for their competence to screen cervical smears, regardless of their standing in the laboratory hierarchy or their experience of gynaecological cytopathology.
Methods. Each participant was asked to screen and report on 10 slides during a 2 h period. the assessment was carried out by a facilitator under the direction of a specially appointed EQA Committee. A maximum score of 20 points was awarded for a completely correct set of answers. A minus score was awarded for a missed abnormal smear. Seventeen pathology laboratories in North West Thames Regional Health Authority participated; 146 cytologists were assessed.
Results. A pilot and four rounds of EQA have been completed and a total 5350 smears examined. Out of 2568 dyskaryotic (abnormal) smears screened, 0.7% were not identified correctly. of the 146 cytologists taking part in the assessment, 95% achieved a score of 17 or more. Three participants were identified who did not reach an acceptable level of competence and appropriate remedial action was taken.
Conclusion. the EQA scheme detected unacceptable levels of performance which can be quickly rectified. Participation of 100% has been maintained on a voluntary basis, and 4 years experience of the scheme confirms that a very high standard of screening prevails in the Region. the study illustrates that voluntary self-regulation is acceptable in the NHS, and the introduction of similar EQA schemes on a national scale will go a long way to establishing confidence in the cervical cancer screening programme.