CYTOLOGIC DETECTION OF CERVICAL CANCER—Four Years' Experience with Routine Smear Examination in Private Practice

Simplified Papanicolaou smear techniques appear to be adaptable to private clinical practice when experienced cytodetection laboratory facilities are available. A private physician''s office seems potentially an efficient, economical and practical place for detection of cervical cancer by use of the smear technique as a routine part of examination of patients.In a series here reported upon, examination of 11,207 cervical smears taken at the first examination of patients of all ages led to diagnosis of unsuspected malignant disease in 80 cases—in all instances at a stage when it should be easily curable. Cancer was not detected in examination of 6,060 smears taken later from women who had had a “negative” smear at the time of first examination, which seems to indicate that the first screening was reasonably accurate.In a few cases, early cancer was detected when smears were reported as “atypical” or “suspicious.” Such reports demand as careful follow-up as do “positive” reports.There are dangers and limitations in wide-spread clinical application of screening by this method. Care must be observed in the development of programs for its use lest the potential benefits in early detection be outweighed by the dangers from misuse.     

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).     

Relationship between the diagnosis of epithelial abnormalities and the composition of cervical smears

The significance of endocervical columnar cells as a high-quality parameter of cervical smears was studied. In a cohort of women with two successive screenings, the consistency of the cellular composition of the cervical smears and the relation between the cellular composition of the smears and the frequency of the diagnosis of abnormal epithelial changes was investigated. At the first screening, a significantly higher number of epithelial abnormalities was found in smears with endocervical columnar cells than in smears without endocervical columnar cells. A significantly higher number of abnormal epithelial changes was found on the second screening in smears from women whose smears from the first screening did not contain endocervical columnar cells than in smears from women whose smears from the first screening did contain endocervical columnar cells. The presence of endocervical cells should be considered a very important indicator of the quality of cervical smears. The chance of missing an abnormal epithelial change is increased in smears without endocervical columnar cells. When endocervical columnar cells are absent, the smear should be considered to be of unreliable quality and a repeat smear should be taken after a short interval, unless the absence of columnar cells can be satisfactorily explained.     

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.     

Review of cervical smears from 76 women with invasive cervical cancer: cytological findings and medicolegal implications

OBJECTIVE: To review cervical smears from 76 women which were taken prior to the diagnosis of invasive cervical cancer and to determine the appropriateness of the cytology reports issued on the smears. METHODS: Cervical smears, clinical records, cervical smear history and cytology reports from 76 women with invasive cervical cancer were reviewed. After microscopic review of the cervical smears, the cases were divided into two groups: Group 1 comprised 50 women who were found to have had at least one false-negative (F/N) smear report prior to the diagnosis of invasive cervical cancer. Group 2 comprised 26 women for whom no evidence of F/N reporting was found. RESULTS: A total of 209 cervical smears from the 50 women in group 1 were available for review (range 2-12 smears per woman); 100 of the 209 smears were considered to have been reported appropriately. Ninety-seven smears which had been reported originally as negative or inadequate were found, on review, to contain numerous severely dyskaryotic cells and were reclassified as F/N smears. All of the 50 women had at least one F/N smear and 29 had two or more. Twelve smears from eight women contained only a few (<200 severely dyskaryotic cells). Forty women developed invasive squamous carcinoma and 10 developed invasive adenocarcinoma. The stage at diagnosis ranged from 1A to stage 4. Seventy-one smears from the 24 women in group 2 were available for review (range 1-15 smears per woman). In two cases included in group 2, no smears were provided for review as the smears had been lost or mislaid. Review of the 71 smears confirmed the accuracy of the original cytological classification of the smear. Nineteen women were diagnosed with squamous cancer, two microinvasive cancer, one glassy cell, two adenocarcinomas, and one with adenosquamous carcinoma. One women was found to have an embryonal rhabdomyosarcoma of the corpus uteri involving the cervix. DISCUSSION/CONCLUSION: The medicolegal implications are discussed in the light of the above findings. Evidence of breach of duty of care was presented in all 50 cases in group I although causation was not established in every case. There was no evidence of failure of duty of care in terms of the standard of the cervical cytology reports issued or standard of clinical management in 17 of the 26 cases in group 2. However, in seven of the 26 cases in group 2, clinical management of the case was substandard due to failure to investigate symptoms of irregular bleeding regardless of a negative cytology report (two cases), failure to act upon a suspicious smear report or consecutive inadequate smear reports (two cases), failure of follow-up after treatment of CIN3 (two cases) and histological misdiagnosis (one case).     

Adherence to recommendations for early repeat cervical smear tests.

OBJECTIVE--To assess adherence to recommendations for an early repeat cervical smear test in women with reports of cytological abnormalities, and to evaluate the impact of reminder letters to medical practitioners when such smear tests are overdue. DESIGN--Observational study. SETTING--Cytology (gynaecological) service for Victoria, Australia. SUBJECTS--Two groups of women who had abnormal cervical smears during 1985. Women in group A had some evidence of an important dysplasia and were advised to have a repeat smear in three months'' time whereas women in group B had a less serious abnormality and were advised to have a repeat smear test in six months'' time. In all, 971 of the 1036 women in group A and 1401 of the 1464 women in group B were eligible to have a repeat smear analysed by the service. INTERVENTION--If a repeat smear had not been received within three months of the recommended date a reminder letter generated by the service''s computer was sent to the medical practitioner who had taken the smear. END POINT--Thirty six months after the report on the abnormal smear was issued. MEASUREMENTS AND MAIN RESULTS--In all, 870 (90%) of the women in group A and 1154 (82%) of the women in group B had a repeat smear test. The mean time to a repeat test was 3.0 months (95% confidence interval 0.5 to 16.4) in group A and 6.0 months (1.2 to 30.3) in group B. The reminder letter to the practitioner potentially increased the rate of return for a repeat smear test by 18% in group A and 24% in group B. Adherence to the recommendation for a repeat test increased with increasing age. CONCLUSIONS--Achieving high rates of follow up smear tests and appropriate management in women with cytological abnormalities is critical to the impact of a screening programme for cervical cancer. The reminder system used in this study was not labour intensive or expensive and provided a fail safe mechanism for ensuring that reports of abnormal smears were not overlooked.     

Quality grading for cervical smears

Three thousand five hundred and eighty cervical smears were taken in 1990–1992 at a Genitourinary Medicine Clinic with various spatula or spatula brush combinations. the unsatisfactory rate and the detection of cellular abnormalities showed some relation to spatula type. However, the satisfactory smears screened in the laboratory are routinely assigned a quality grade-good, fair or poor. Analysis shows higher rate of detection of cellular abnormalities in good quality smears, the detection of dyskaryosis being twice as high, in contrast to the fair or poor quality smears. It is suggested that quality grade is a better way of classifying smear quality in the cervical screening programmes rather than the presence or absence of endocervical and/or metaplastic cells.     

Should smears in a colposcopy clinic be taken after the application of acetic acid?

Conventionally, cervical smears obtained during a colposcopic examination are taken before the application of acetic acid. However, this occasionally precipitates bleeding and removes epithelium from the cervix, particularly in the presence of cervical pathology, making colposcopic evaluation difficult. This study examined the possibility of deferring the smear until the end of the colposcopic examination. In the first part of the study, the cytologic results on cervical samples taken from the same patient before and after the application of acetic acid were compared. In the second part of the study, only one smear was taken per patient (either before or after colposcopic assessment) to eliminate the possibility that the taking of the first smear affected the quality of the second. The results of both parts of the study showed that deferring the smear until after the application of acetic acid leads to an unacceptably high rate of unsatisfactory and falsely negative smears. Thus, deferring the taking of the cervical smear until after the colposcopic evaluation results in a poor cytologic evaluation, although it might facilitate the colposcopic examination in some patients.     

The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical Screening Programme

Objective: To examine how NHS cervical screening data can be collected and analysed in order to evaluate women’s screening histories as episodes rather than as individual smears. Design: Analysis of routine cervical screening data grouped into screening episodes for a cohort of women regarding episodes starting in a given year. Setting: NHS Cervical Screening Programme. Population: Data from four Health Authorities (now eight Primary Care Trusts) from the NHS Cervical Screening Programme with primary smears (first in an episode) taken between 1 April 1999 and 31 March 2000. Methods: Cytology information obtained from the call/recall (‘Exeter’) computer system was linked to cervical intraepithelial neoplasia (CIN) 3 and invasive cancer outcome information obtained from cancer registries. Screening histories were divided into episodes, each starting with a primary smear that was followed up to episode closure or, for episodes still open followed for an average 4.25 years, from the primary smear. The episode was divided into two parts (up to referral to colposcopy and following the referral). The outcomes of the episodes are described including referral rate to colposcopy and CIN3 and invasive cancer rates by factors such as age. Main outcome measures: Episode histories and rates of referral to colposcopy, CIN3 and invasive cancer. Results: There were 176 923 episodes from 176 319 women (1.003 episodes per woman) followed up to March 2004, the date at which the first phase of information accrual ceased. Of these episodes, 172 100 (97.3%) were closed either by a negative smear referring the woman back to routine recall or by default (defined as no smear recorded within 21 months following a smear requiring an action of repeat or refer to colposcopy). The remaining 4823 (2.7%) of episodes were still open, of which in 3121 (1.8%) the woman had been referred to colposcopy and in 1702 (1.0%) no referral decision had been made. Referral rates to colposcopy varied by age from 5.7% in women aged 20–24 years down to 0.9% in women aged 60–64 years. The overall efficiency of screening was highest for woman aged about 30 years, with a CIN3 detection rate of eight per 1000 women and a positive predictive value (for CIN3 or worse) of referral to colposcopy of 21%. Conclusion: The study has shown that routinely collected NHS cervical screening data can be combined to give information on complete episodes, allowing important performance measures to be studied. We suggest that in future information in the NHS screening system should be structured to facilitate such analysis and to allow cytology and histology information to be readily linked.     

Cell block as an adjunct to conventional Papanicolaou smear for diagnosis of cervical cancer in resource-limited settings

OBJECTIVE: To assess the utility of indigenously prepared cell blocks (CBs) as an adjunct to a conventional smear test in providing a reliable diagnosis of clinically suspicious cervical cancer in resource-limited settings. METHODS: Eighty-six clinically suspicious cervical cancer cases underwent a conventional smear test, CB preparation from residual cellular samples and biopsies at the same sitting. Correlations were performed between these modalities in order to derive the sensitivity and specificity of the CB technique to diagnose cervical cancer. OBSERVATION & RESULTS: Out of 86 clinically suspicious cervical cancers, 72 (83.7%), 70 (81.4%) and 67 (77.9%) cases were diagnosed as malignant on tissue biopsies, CBs and smears respectively. CB-biopsy agreement in the diagnosis of malignancy was feasible in 87.5% of the cases while CB-Pap smear agreement was feasible in 92.5% of the cases. Sensitivity and specificity of CB preparation to diagnose malignancy was 92.5% and 100%, respectively, when the smear was taken as the reference test (excluding the unsatisfactory smears). When biopsy was taken as the gold standard, the sensitivity and specificity of CBs were 87.5% and 100% respectively (excluding the unsatisfactory biopsies). In 8/19 cases where the smear diagnoses were either unsatisfactory or atypical squamous cells/atypical glandular cells, CBs picked up malignant lesions. CONCLUSION: CBs prepared from the residual cellular sample of conventional cervical scrapes augment the sensitivity of the smear test. When used as an adjunct to the smear, CBs aid in providing a reliable diagnosis of cervical cancer in the majority of the clinically suspected cases and thus the biopsy load can be reduced significantly in resource-poor settings.     

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.     

Adenoid cystic carcinoma of the uterine cervix. Cytologic features

A case of primary cervical adenoid cystic carcinoma in a 75-year-old woman is reported. Two cervical smears taken at the time of initial presentation for vaginal spotting were negative; a third smear, taken a year later prior to laparotomy, was diagnosed as positive. The cytologic findings in the positive cervical smear are described and illustrated. The differential diagnosis of the cytologic findings is discussed, and the literature on this lesion is briefly reviewed. The results in this case and others suggest that the diagnosis of cervical adenoid cystic carcinoma in an asymptomatic patient may be missed by routine smear examination.     

Association between cervical lesion grade and micronucleus frequency in the Papanicolaou test

The aim of this study was to evaluate the association between the frequency of micronuclei (MN) and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001). The mean MN frequencies were 0.95 ± 1.12 (mean ± SD) in the control group (n = 223), 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US) (n = 50), 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN) I (n = 52), 5.97 ± 1.83 in CIN II (n = 30), 7.29 ± 1.55 in CIN III (n = 17) and 8.64 ± 1.55 in invasive cancer (n = 25). These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal.     

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.     

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.     

Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia

A. Repše‐Fokter, A. Pogačnik, V. Snoj, M. Primic‐Žakelj and M. S. Fležar
Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia Objective: The purpose of the study was to perform a national review of negative, low‐grade and inadequate smears reported during the latest screening period before cervical cancer diagnosis in 2006, after the first 3 years of the screening programme. Methods: Among 162 new cervical cancer cases there were 47 (29%) without previous cytology, 47 (29%) with one high‐grade smear prior to diagnosis and 68 (42.0%) with at least one previous negative, low‐grade, atypical or inadequate smear 1–40 months before diagnosis. Of the latter 68 cases, 37 patients with 59 smears (together with 118 control slides) were included in the review as 31 had smears reported at laboratories no longer operating. Findings were related to the last cytology report before diagnosis as well as to histological type and stage of the cancer. Results: In our study group, 19 (51%) of 37 patients had squamous cell carcinoma, 15 (41%) adenocarcinoma and 3 (8%) adenosquamous carcinoma, compared with 121 (75%), 26 (16%), 12 (7%), respectively, and 3 (2%) other types, for all carcinomas. Twenty‐one of 37 women also had high‐grade cytology prior to diagnosis of cancer. Women with previous cytology (with or without recent high‐grade smears) were more likely to have stage I cancers than those without cytology (P < 0.0001). The expert group upgraded 17/33 smears in the patients with squamous carcinomas, which was more than in those with adeno‐ and adenosquamous carcinomas (5/24, P < 0.05). Conclusion: As expected, a higher proportion of smears preceding adenocarcinomas were true negative. Under‐diagnosed smears were not related to cancer stage or last cytology report before diagnosis.     

Papanicolaou smears without endocervical cells. Are they inadequate?

The retrieval of columnar endocervical cells from the squamocolumnar junction has generally been considered to be a measure of the adequacy of a Papanicolaou smear; this implies that, if endocervical cells are absent from the smear, the examination for cervical cancer is less than optimal and should be repeated. A study was undertaken to determine if women with serial Papanicolaou smears without endocervical cells showed an increased rate of development of cervical atypia in subsequent smears. The smears of 18,914 women were evaluated for the presence or absence of endocervical cells and for the subsequent development of an abnormal smear over a four-year study period. No differences were found in the rates of atypia between women with and those without endocervical cells on serial Papanicolaou smears. Women with prior Papanicolaou smears without endocervical cells were much more likely to have a subsequent Papanicolaou smear without endocervical cells. Although no difference was found in the incidence of cervical atypia in the two groups during this short study period, these results should be considered to be preliminary.     

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.     

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.     

Histologic and clinical characteristics associated with rapidly progressive invasive cervical cancer: a preliminary report from the Yale Cancer Control Research Unit

Histologic and clinical characteristics associated with rapidly progressive invasive cervical cancer are presented in this preliminary report from a population-based study involving all patients in Connecticut diagnosed with cervical cancer from March 1, 1985. Rapidly progressive invasive cervical cancer, i.e., invasive cancer diagnosed within three years of a true negative Pap smear, is more likely to occur in younger women with high annual incomes (61 percent greater than $40,000) who report a greater frequency of benign gynecologic conditions (uterine leiomyomata, vaginitis) compared to a control cervical cancer group. These preliminary data suggest that as many as 35 percent of the rapidly progressive cervical cancers are likely to be adenocarcinomas. Because they are mostly endocervical in origin, they may not be detected cytologically if scrapers or cotton swabs are used to sample the endocervical canal. New cytologic screening techniques using brushes may identify these lesions earlier and should routinely be employed in cytologic screening for cervical neoplasia. The difficulty in early detection of this form of the disease requires that physicians rapidly assess patients with unexplained pelvic and lower abdominal pain, vaginal discharge, or abnormal vaginal bleeding since early recognition is the only chance for cure. Further analyses of this population of women will be made to identify additional risk factors when the study data are complete.