Computer-assisted primary screening of cervical smears using the PAPNET method: comparison with conventional screening and evaluation of the role of the cytologist

The PAPNET method is an interactive computer-assisted screening procedure. the diagnostician selects the abnormal video tiles out of the 128 and decides which smears need additional light microscopy. the original diagnoses of 1494 archival smears were compared with the PAPNET analysis of the same smears. the general trend observed was that the PAPNET-assisted diagnoses were of a higher grade than those assigned by the primary screener, thus less cases were signed out as negative. In addition, the PAPNET method was used for primary screening of 2971 randomly selected smears, whilst in the same period 5797 smears were conventionally screened. Using the PAPNET method, significantly fewer smears were signed out as negative. Seventy-three percent of the cases were diagnosed on the basis of the information provided by the 128 video tiles, 11% had to be screened completely by the light microscope, and the remaining cases needed additional light microscopy of a part of the smear. As a result, PAPNET-assisted screening was approximately two times faster. the great advantage of the method is that it is much less tiring for the eyes than conventional screening, making fatigue-related errors less likely, and if a smear contains only a few abnormal cells, these are easier to find.     

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.     

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.     

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.     

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.     

The preparation of additional smears from a cervical scrape: impact on the rate of detection of cervical neoplasia

The preparation of additional smears from a cervical scrape: impact on the rate of detection of cervical neoplasia It has been known for some time that only a proportion of the cells on the smear-taking device is transferred to the slide. This can give rise to errors in reporting although the smear may have been taken correctly. This study was undertaken to identify a quick and simple method of improving the accuracy of the Papanicolaou test. A conventional smear and five additional smears were obtained from 62 women attending a Genito-Urinary Medicine clinic. The cell content of the conventional smears and the additional smears was compared. Dyskaryotic cells were detected both in the conventional smear and in the first and second additional smears from 22 women. Dyskaryotic cells were detected in the first and second additional smears only in five women. Thus, the conventional smear failed to detect biopsy-confirmed cervical abnormality in these women. A cell count of the first additional smear in the five cases where the conventional smear was negative showed that they contained, on average, 310 dyskaryotic cells. The preparation of one additional cervical smear per cervical scrape could significantly increase the accuracy of the cervical smear test by 11% (P=0.025, McNemar's test).     

Quality assurance in cervical smears: 100% rapid rescreening vs. 10% random rescreening

OBJECTIVE: To compare 100% rapid rescreening of cervical smears with 10% random rescreening as a method of quality assurance. STUDY DESIGN: A total of 5215 smears, randomly selected from smears reported as negative by cytotechnologists during routine screening, underwent 100% rapid rescreening by senior cytotechnologists. Ten percent of these smears, selected at random, were rescreened by other senior cytotechnologists. The gold standard was defined by cytopathologists, who rescreened all 5215 smears. After excluding unsatisfactory smears detected by cytopathologists, 4271 were included in the analysis. RESULTS: The 100% rapid rescreening method identified 69.9%, 95.7% and 100%, respectively, of atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion and high grade squamous intraepithelial lesion cases reported by the cytopathologists. The 100% rapid rescreening method showed a sensitivity of 73.5% and specificity of 98.6%. The 10% rescreening method showed sensitivity of 40.9% and specificity of 98.8%. CONCLUSION: One hundred percent rapid rescreening is an efficient method of internal quality assurance in cervical smear diagnosis. It can reduce the false negative rate and therefore can provide greater certainty to women who have received negative results. Well-trained cytotechnologists are able to identify abnormal smears in 1-minute rapid rescreening.     

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.     

Rapid cervicovaginal smear screening: method of quality control and assessing individual cytotechnologist performance

AIM: To validate the method of rapid screening (RS) in the detection of cervical lesions and false-negative results as well as in quality control of cytotechnologist performance. MATERIAL AND METHODS: The RS method was validated on Papanicolaou-stained and initially conventionally analysed vaginal, cervical and endocervical (VCE) smears collected in an opportunistic programme for the detection of cervical carcinoma. The study included 3680 VCE smears from the Department of Gynaecologic Cytology, University Department of Gynaecology and Obstetrics, Zagreb University Hospital Center, Zagreb and from the Department of Clinical Cytology, Osijek University Hospital, Osijek. Histologically verified abnormal findings accounted for 10% of the study samples. Thirteen cytotechnologists, with no previous experience in RS, performed the test. Each slide was examined using the 'step' technique for 1.5 minutes, the findings were classified as negative or abnormal, and the abnormal ones were also classified according to differential cytological diagnosis. The results were compared with those obtained on initial screening. Abnormal findings from a group of initially negative findings were reanalysed using conventional methods to make definitive cytological diagnosis. RESULTS: RS yielded a sensitivity of 83.7%, specificity of 93.7%, positive predictive value of 62.4%, negative predictive value of 97.9% and diagnostic accuracy of 92.6%. Relative to the initial abnormal differential cytological diagnosis, the diagnostic value of RS increased with lesion severity [54.8%, 68.0% and 91.3% for cervical intraepithelial neoplasia (CIN) I, CIN II and CIN III respectively]. RS detected 38 additional positive findings; 94.2% of these were atypical squamous cells of undetermined significance (ASCUS)/abnormal glandular cells undetermined significance (AGUS) and CIN I. The rate of additional positive findings was 1.14% (38/3135). The false-negative rate of initial screening was 9.4% (38/406), and individual cytotechnologist sensitivity was 60.0-100.0%. CONCLUSION: RS could be introduced as an efficient method of quality control to improve the sensitivity of cytological screening as well as for quality control of cytotechnologist performance.     

Quality assurance in cytopathology. Recommendations and ongoing quality assurance activities of the American Society of Clinical Pathologists

The recommendations and activities of the American Society of Clinical Pathologists (ASCP) pertaining to quality assurance in cytopathology are reviewed. To assure the early detection of cervical cancer, the ASCP recommends that all women who are, or have been, sexually active should have an annual Papanicolaou smear examination, the reasons for which are discussed. To assure the optimal quality in the evaluation of these smears, the ASCP recommends that the screening should be performed (1) in an accredited laboratory by certified cytotechnologists, (2) for whom realistic workloads have been established, (3) under the supervision of a pathologist adequately trained in cytology, (4) who will maintain an ongoing quality assurance program. In addition, (5) Papanicolaou smear evaluations should be available to all patients at a reasonable cost and (6) the financial incentives for the performance of low-quality screening should be eliminated. The society's quality assurance activities discussed include the Check Sample program, self-assessment examinations, meetings and publications; planned additions to this arena include a challenge exam and proficiency survey mechanisms.     

Real-World Efficiency of Pharmacogenetic Screening for Carbamazepine-Induced Severe Cutaneous Adverse Reactions

Objectives

We evaluated the cost and efficiency of routine HLA-B*15∶02 screening to prevent carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-SJS/TEN) in Hong Kong.

Methods

Data were extracted from patients who commenced CBZ as the first-ever AED treatment or tested for HLA-B*15∶02 allele in three years before policy implementation (pre-policy: 16 September 2005 to 15 September 2008) and three years after (post-policy: 16 September 2008 to 15 September 2011). Using published unit costs, we estimated the cost of screening by comparing the costs to prevent and treat CBZ-SJS/TEN. We compared the number of person-tests needed and the cost to prevent resultant death with cancer screening programs.

Results

The number of screening tests needed to prevent one case of CBZ-SJS/TEN was 442, and to prevent one resultant death was 1,474 to 8,840. The screening cost was $332 per person, of which 42% was attributed to an additional consultation to review result and prescribe appropriate medication. HLA-B*15∶02 screening expended $146,749 to prevent a case of CBZ-SJS/TEN, and $489,386– $2,934,986 to prevent a resultant death. The corresponding numbers of tests and costs for mammography and Pap smear to prevent death due to breast and cervical cancers were 7,150 and 7,000, and $614,900 and $273,000, respectively. Comparing to the SJS/TEN treatment cost, HLA-B*15∶02 screening would become cost saving if a point-of-care test of less than $37 was available.

Conclusions

HLA-B*15∶02 screening is as efficient as mammography and Pap smear in preventing death. Development of point-of-care testing will vastly improve efficiency.     

Liquid-based cytology can improve efficiency of cervical smear readers: evidence from timing surveys in two NHS cytology laboratories

OBJECTIVE: Cervical screening programmes in England and Wales were advised by the National Institute for Clinical Excellence in 2003 to adopt liquid-based cytology (LBC) in place of conventional Papanicolaou (Pap) cytology to facilitate laboratory efficiency. Pilot evaluations in England and Scotland monitored daily or weekly workloads of smear readers and concluded that LBC could increase hourly throughput rates. This study, instead, used timing surveys to determine screening rates. METHODS: Two National Health Service cytology laboratories in Manchester and Stockport were partially converted to the LBC ThinPrep process for a cervical screening trial. Three 1-week timing surveys were conducted over 7 months. The surveys covered all LBC-trained staff. The first survey in Manchester also covered staff undertaking conventional Pap screening. The smear readers used timers to record time taken for examining and reporting each slide. RESULTS: In Manchester, in the first survey, nearly 1 minute per slide was saved by the LBC method during primary microscopy. In both laboratories, the mean microscopy time for primary screening of LBC slides was reduced by almost 1 minute between the first and second surveys. There was no difference between the second and third surveys. Microscopy by cytopathologists was also 1 minute per slide quicker with LBC than conventional Pap. The LBC inadequate rates for both laboratories were <2.0%. Organizational factors impacted on the hourly LBC primary screening rates in the laboratories, the rate for Stockport being higher than the rates in the pilot evaluations. CONCLUSIONS: The timing surveys confirm that the LBC ThinPrep technology can improve laboratory efficiency. However, decision-makers should also consider the overall costs and benefits of introducing the technology in screening programmes, including the capital investment and workforce implications.     

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.     

Variation in the assessment of adequacy in cervical smears

OBJECTIVE: To assess the interobserver reproducibility of the diagnosis of 'adequacy' of cervical smears according to the Bethesda System criteria in cervical smears. STUDY DESIGN: 358 cervical smears were obtained from three Italian cytopathological centres in 1998-99. All centres provided consecutively collected smears. The cervical smears were independently and blindly assessed by four cytologists.The screening was performed using a 10x objective and an additional evaluation of the percentage of cellularity was performed using a 4x objective. RESULTS: The proportion of smears assessed by the four cytologists as 'adequate' ranged from 60% to 70%, the proportion of 'satisfactory for evaluation but limited by' ranged from 27% to 38%, and the proportion of 'inadequate smears' ranged from 2% to 4%. Full agreement in the assessment of smear adequacy was observed in 311 slides and disagreement was observed only in 47. The category 'inadequate smear' was less reliable than the other two; however, the kappa value observed was acceptable. CONCLUSION: The present study shows that it is possible to achieve a high reproducibility in the assessment of smear adequacy, at least among expert cytologists who follow the Bethesda System criteria strictly.     

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.     

Evaluation of the AutoCyte SCREEN system in a clinical cytopathology laboratory

OBJECTIVE: To compare the AutoCyte SCREEN (AutoCyte, Burlington, North Carolina, U.S.A.) system with manual screening by experienced cytotechnologists using thin-layer preparations that had been previously extensively studied and their cytologic abnormalities well defined. STUDY DESIGN: AutoCyte PREP (AutoCyte) samples prepared for a previous split-sample study comparing thin-layer preparations to conventional smears were used. These 1,992 AutoCyte PREP samples were in a cohort the abnormal findings of which had been confirmed via independent review by two sets of pathologists. For the current study, these samples were remasked and evaluated by the AutoCyte SCREEN system in a clinical laboratory. The instrument scanned each slide and selected six overview fields and 120 single objects for storage and display. The computer classified each slide in one of the following categories: abnormal, uncertain, normal or unsatisfactory. Independently for each case, a cytotechnologist evaluated the six fields and 120 objects selected by the instrument as abnormal, normal or unsatisfactory. For those cases classified as uncertain by AutoCyte, the technologist then reexamined the cellular displays and entered a consensus classification. These results were then compared to those of an independent review by cytotechnologists of the identical set of slides using routine manual screening. RESULTS: The AutoCyte SCREEN selected 35% of slides for manual review. Technologist and computer rendered equivalent classifications in 79%. Of the total slides screened by the AutoCyte SCREEN, 57% were classified as "uncertain," and 88% of these were subsequently classified as normal by consensus. Using the well-defined abnormal values of the cellular sample as a basis for calculation, the AutoCyte SCREEN-assisted practice had a diagnostic sensitivity of 85% and diagnostic specificity of 97.6%. Comparable values for manual screening of the identical cellular sample were a diagnostic sensitivity of 80% and specificity of 97.4%. CONCLUSION: The AutoCyte SCREEN achieves comparable or greater sensitivity in detecting cervical abnormalities in comparison with manual screening. When combined with the substantial advantage of thin-layer preparations over conventional smears, the AutoCyte SCREEN provides a screening system of superior sensitivity over conventionally prepared and examined cervical smears.     

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.     

Collagen balls in cervical smears. A previously undescribed finding

OBJECTIVE: To evaluate several conventional cervical smears obtained from women undergoing routine screening for cervical dysplasia or carcinoma and whose smears contained structures resembling collagen balls. STUDY DESIGN: Between 1995 and 1998, cervical smears containing collagen balls were analyzed. The clinical histories of the patients whose smears contained collagen balls, including the gestational history, were reviewed. Histopathologic material from any related surgical specimens was reviewed, with special attention to mesothelial surfaces. RESULTS: Collagen balls were found in 5 of 77,891 Pap smears examined (0.006%). None of the patients had evidence of neoplasms of the genital tract. One of the patients was in the first trimester of pregnancy. CONCLUSION: We suggest that collagen balls in cervical smear originate in mesothelium-covered organs, from where they are transported via the fallopian tubes into the uterine cavity. Their significance lies in their being mistaken for mucin-distended cells exfoliated from a neoplasm or from detached fragments of a papillary ovarian neoplasm.     

Cervical cytology screening in Vietnamese asylum seekers in a Hong Kong detention center. Population demographics and historical perspectives

OBJECTIVE: To provide a brief review of the history and demographics of the Vietnamese asylum-seeking population in Hong Kong and their possible effects on the initiation of a cervical cytology screening program at a Hong Kong detention center. STUDY DESIGN: Analysis of case histories, questionnaires and interviews with women in a detention center identified demographic features related to Pap smear history, knowledge of the Pap test, age at first intercourse and cigarette smoking status among women aged 17 years and over. Analysis of Pap smear uptake following initiation of a screening program was undertaken. RESULTS: Of the 1,171 women in the detention center who were eligible for a Pap smear, 536 (45.8%) actually obtained one, although enrollment, which was strong at the initial offering, slowed considerably as the program progressed. None of the women had had a Pap smear prior to leaving Vietnam. Knowledge of the utility and risk status criteria for Pap testing was very limited. The majority (77.9%) of the subjects started sexual activity after age 20 years, and three (0.6%) smoked. There were four (0.2%) abnormal smears identified among those tested. CONCLUSION: Convincing evidence was obtained that the Pap test was not widely used in Vietnam among the asylum-seeking population, and its role in preventing cervical cancer was not well known to the women studied. The initial strong uptake of the Pap smear was not maintained. That may be attributable to psychosocial factors associated with detention under harsh conditions and trauma associated with fleeing Vietnam.     

An Audit of Cervical Cancer Deaths In Nottingham

Death certificates were reviewed and 57 women were identified whose primary cause of death was cervical cancer. Their cervical smear records were reviewed from laboratory files. Only nine had participated in the cervical cancer screening programme before the diagnosis of cervical cancer was made. One woman had an abnormal smear as a result of cervical screening but failed to attend for follow-up.
The problem of false negative smears is also addressed and the value of review of negative smears for the purposes of cytology audit is emphasized.