Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer

OBJECTIVE: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma. STUDY DESIGN: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer. RESULTS: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions. CONCLUSION: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.     

CytoView. A prototype computer image-based Papanicolaou smear proficiency test

OBJECTIVE: To develop and assess CytoView, a prototype computer image-based cytology proficiency testing (PT) system, as an alternative to glass-slide cervical cytology PT. STUDY DESIGN: The computer-based PT consists of 10 cases taken from 10 Pap smears, each of which had received a consensus Clinical Laboratory Improvement Amendments-category diagnosis from three pathologists. Each CytoView "case" was the digital representation of > 8,000 microscopic fields, captured from a selected 5 x 10-mm rectangle of a Pap smear. The 5 x 10-mm capture rectangle was selected from the slide's most representative area for its diagnostic category. The CytoView project team developed each case through a multistep process that included image capture, image alignment, correlation of 10x and 40x images, and image display. The 10-slide CytoView PT prototype was then assessed by groups of cytopathologists and cytotechnologists. RESULTS: The CytoView prototype PT system was developed and assessed. CONCLUSION: Preliminary evaluation of CytoView indicated potential for this format as a valid and logistically feasible alternative to the traditional glass slide PT format.     

Is a liquid‐based cytology more sensitive than a conventional Pap smear?

K. Sigurdsson
Is a liquid‐based cytology more sensitive than a conventional Pap smear? Background: The comparative sensitivity of liquid‐based cytology (LBC) test and conventional Papanicolaou (Pap) smears is controversial. Material and methods: This study analyses the distribution of cytology, histology, colposcopy and large loop excision of the transformation zone among women screened in Iceland with LBC at the Cancer Detection Clinic in Reykjavik and with a conventional Pap smear outside the Detection Clinic in 2007–2011. The study material included 42 654 LBC tests from 20 439 women and 103 909 Pap smears from 61 574 women. The period 2000–2004 is used to correct for potential bias as a result of unequal distribution of the studied parameters between the study sites before the introduction of LBC. Results: The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears, increased detection of low‐grade squamous intraepithelial lesion (LSIL)/atypical cytology and referrals to colposcopy, and an increased detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) irrespective of age. LBC increased significantly the detection rates of high‐grade squamous intraepithelial lesion or worse (HSIL+) cytology and CIN3+ histology only in women under 40 years of age. Taking into consideration the unequal prevalence of the studied parameters between the study sites in 2000–2004 indicated, however, that LBC only affected the rate of inadequate and low‐grade cytology tests under the age of 40 years. Positive predictive values for CIN2+ were not significantly different between the tests. Conclusions: The study results support the view that LBC is no more sensitive than Pap smears for the detection of HSIL+ and CIN2+ irrespective of age. LBC decreased the rate of inadequate smears, but increased the rate of low‐grade cytology under the age of 40 years and decreased the total rate of abnormal smears over the age of 40 years.     

Effect of circulation and discussion of cervical smears on agreement between laboratories

The study objective was assessing whether circulation of smears and discussion of those with differing interpretation can increase reproducibility between laboratories. The study included: the blind interpretation of a first set of 194 smears among seven laboratories, the discussion of smears with discrepant diagnoses during the previous phase and the blind interpretation of a second set of smears of same size and characteristics. After discussions, the overall weighted kappa increased in five laboratories (substantially in three : +50%, +27% and +20%). However, no change was observed in one laboratory and a slight decrease (-4%) in another. The latter interpreted the second set of smears at a longer time interval from discussions. Agreement improved for all diagnostic classes except low grade intraepithelial neoplasia (LSIL). Overall, the intervention increased diagnostic agreement, but its effect varied with laboratory and by diagnostic class and could be transient. Continued programmes of smear exchange and discussion appear to be advisable.     

Cytology and clinical spectrum of sexually transmitted infections in Lebanese women as revealed by Pap smear: a cross-sectional study from 2002-2006

To study the cytology profile of cervical smears and the respective prevalence and incidence of certain cervico-vaginal infections detectable by routine Pap smear cytology in Lebanese women from 2002 to 2006. Pap smear cytology results were compiled from the archives of the Institut National de Pathologie for the period extending from 2002 until 2006. This study covered 118,230 cervical specimens obtained from Lebanese women attending clinics and hospitals in all the five districts of Lebanon; prevalence and incidence rates for infections detectable by routine Pap smear examination were determined. A rise in prevalence of these infections by 2.1 percent (2,555) from 2002 to 2006 was revealed. A doubling of Pap smears showing HPV-associated changes was detected (1.4 percent in 2002 to 2.9 percent in 2006), and a simultaneous almost 7-fold increase of Atypical Squamous Cells of Undetermined Significance (ASCUS) cytology was detected during this period; the rise in ASCUS cytology was age-dependent. Moreover, a 60 percent increase in prevalence of bacterial vaginosis (2.3 percent in 2002 to 3.7 percent in 2006) and a more than 3-fold decline in Trichomonas vaginalis infection (1 percent in 2002 to 0.3 percent in 2006) were also noted in this population during this period. An increase in the prevalence and incidence of cervico-vaginal infections detectable by Pap smear cytology in Lebanese women was revealed from 2002 to 2006. Such changes could point to recent modifications of sexual and health behaviours in the Lebanese community.     

Interlaboratory reproducibility of atypical glandular cells of undetermined significance: a national survey

OBJECTIVE: The aim of this study was to evaluate the inter-laboratory reproducibility for atypical glandular cells (AGC) (The Bethesda System (TBS) 2001) of the laboratories involved in the screening programmes in Italy. METHODS: A set of 35 selected slides were circulated among 167 laboratories involved in local population-based cervical screening programmes. Each laboratory provided one single diagnosis per smear. The smears were read blind to the original diagnosis and to the diagnoses provided by other laboratories. A 'majority' diagnosis was defined for each case and assumed as the reference standard. The diagnosis provided from each laboratory was compared with the majority diagnosis. RESULTS: According to the majority report the 35 slides in the set were classified as negative in nine cases, AGC in eight, adenocarcinoma in eight, and squamous lesion or squamous + glandular lesion in 10. The crude agreement between all pairs of laboratories was 49.43%. K-values were 0.46, 0.21, 0.34, 0.36 and 0.32 for negative, AGC/AIS (adenocarcinoma in situ of endocervix), AdenoCa, Sq/Sq + Gl and all reporting categories respectively. Concordance according to overall K was moderate to substantial in 77% of the participating laboratories. CONCLUSIONS: The present study shows that the AGC category is not easily reproducible. The data confirmed the importance, in a screening scenario, of AGC/AIS diagnoses, but also presented difficulties in differentiating between the two diagnoses. In addition to the results obtained from the circulation of the slides, laboratories which had annually a low number of cervical smears were able to gain experience focused on particular morphological pictures.     

Survey of smear taking practice in the former North Thames region

One hundred and seventy-seven doctors and 161 nurses from 230 clinics responded to a questionnaire on smear taking practice. The responses show that 66% of smear takers use the Aylesbury spatula and 30% use the Ayre spatula. A total of 53% use a cytobrush for selected cases. Training of smear takers and preparation of smears was satisfactory. Most (but not all) smear takers routinely record clinical information on the request form. Only 20 cytology laboratories in the North Thames region (70%) provide additional feedback to the smear takers about the quality of their smears apart from the information on the request form. Our study shows that feedback is an area where interaction between the laboratory and smear taker could be encouraged.     

Pap smear adequacy--is the assessing criterion including endocervical cells really valid?

The significance of endocervical cylindrical cells (EC) as a criterion of sample adequacy has been established on 1,000 patients by comparing VCE smears (vaginal, cervical, endocervical) with or without EC in relation to prevalence of abnormal cells, prevalence of histological diagnosed lesions and sensitivity and negative predictive value of Pap smear, as well as by comparison of negative findings without EC with control smears with the aim of discovering overlooked lesions. A considerably greater yield of cytological (107/536 in relation to 49/464) and histological (105/536 in relation to 55/464) (p < 0.05) abnormalities in smears with EC support the hypothesis that the presence of EC is strongly and positively associated with prevalence of disease. In contrast, the presence of EC predicts only a moderate improvement in Pap smear quality with a weaker effect on sensitivity (95% in relation to 80%). During two-years monitoring of patients with negative Pap smear and negative colposcopy (403 with EC and 390 without EC in smears), no positive cytology/histology diagnosis was made. Also, because the prevalence of missed lesions among negative Pap smears is extremely low in absolute terms, no appreciable impact on negative predictive value was observed (98.8% in relation to 97.3%).     

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.     

Comparison of cytohistologic techniques in diagnosis of gastroesophageal malignancy

OBJECTIVE: To evaluate the diagnostic performance of various endoscopic cytologic techniques, namely, brushing cytology, touch smear cytology and crush cytology, and comparison with concurrent biopsy results in diagnosis of gastroesophageal malignancy. STUDY DESIGN: This prospective study was conducted on 100 patients, with 78 clinically suspected cases of esophageal malignancy and 22 cases of gastric malignancy. RESULTS: The diagnostic accuracy of touch smear in esophageal malignancy was significantly higher (94.12%) than brushing and crush smears (89.71% each), and endoscopic biopsy had the diagnostic accuracy of 88.24%. The diagnostic accuracy of combined brushing and biopsy was 100%; it was 97.06% for touch smears combined with biopsy. In comparison, the diagnostic accuracy in gastric malignancy was 75% for brushing alone, which was significantly lower than touch smear (87.5%) and endoscopic biopsy (87.5%). The diagnostic yield for crush smear was 81.25%. A combination of touch smears and biopsy had a diagnostic yield of 100%; it was 93.75% for combined brushings and biopsy. CONCLUSION: A combination of cytohistologic techniques resulted in a statistically significant increase in the diagnostic yield of gastroesophageal malignancies and thus cytologic techniques may act as adjunct to biopsy histology to increase the diagnostic efficiency.     

Pap smear screening in women under 30 in the Norwegian Coordinated Cervical Cancer Screening Program, with a comparison of immediate biopsy vs Pap smear triage of moderate dysplasia

OBJECTIVE: Top provide population based estimates of Pap smear screening results among women under 30 and to compare the outcomes of 2 triage options for women under 30 with a moderate dysplastic Pap smear: immediate biopsy vs. Pap smear follow-up. STUDY DESIGN: All Pap smears, histologically verified cervical intraepithelial lesion (CIN) 2/3 and invasive cervical cancer in 1999-2002 from women in Norway under 30 in 2000-2002 were analyzed. Due to different triage recommendations in different laboratories, 836 women under 30 with a moderately dysplastic Pap smear were recommended for immediate biopsy, while 109 were recommended for a Pap smear within 6 months. Risk estimates for triage outcome were estimated by multinominal logistic regression. RESULTS: The prevalence of squamous intraepithelial lesion was highest around 20 years. The first moderate dysplasia was diagnosed at age 16, as was CIN 2/3. Of the women with Pap smear triage, one third were diagnosed with a CIN 2+ lesion, one third had a normal outcome, while the last third were in uncertain state 12 months later. Among those recommended for immediate biopsy, nearly 70% were diagnosed with a CIN 2+, thus having odds of 4.2 (95% CI 2.5-7.1) higher than did women with Pap smear triage of being diagnosed with CIN2+ 12 months later. CONCLUSION: The choice of triage has a profound impact on the proportion of young women diagnosed with CIN 2+ after a moderately dysplastic Pap smear.     

Value of histiocyte detection in Pap smears for predicting endometrial pathology. An institutional experience

OBJECTIVE: To determine the clinical implications of the finding of histiocytes in Pap smears in 1 patient population. STUDY DESIGN: The medical records and Pap smears which the presence of histiocytes was mentioned in the diagnosis between August 1996 and August 2001 were reviewed in conjunction with follow-up surgical findings. The positive predictive value (PPV) for significant endometrial pathology for the isolated finding of histiocytes on Pap smear was determined. RESULTS: Of the 238,225 women screened over a 60-month period, 325 were reported to have histiocytes in their Pap smears. Of them, 238 (73.2%) had subsequent endometrial sampling, hysterectomy or both, and follow-up Pap smears. Two hundred seven smears (87%) failed to disclose endometrial pathology. Thirty-one cases (13%) resulted in significant histopathologic findings, including 12 uterine malignancies, 8 endocervical polyps, 7 endometrial polyps, 2 submucosal leiomyomata, 1 simple hyperplasia without atypia and 1 case of tamoxifen-related changes. Upon review of the clinical records, 58% (18/31) of those patients had other significant clinical and/or cytologic findings. Five of the 18 patients (27.8%) had associated postmenopausal bleeding, 11 had additional abnormal Pap smear findings (atypical glandular cells, 6/18, or 33.3%; endometrial cells, 5/18, or 27.8%), and another 2 had both postmenopausal bleeding and atypical glandular cells (2/18, or 11.1%). The PPV for significant uterine pathology for women with the isolated finding of histiocytes on a Pap smear was 5.5% and 60% with additional clinical and/or Pap smear findings. The PPV for endometrial cancer was 1.3% in women with the isolated finding of histiocytes on a Pap smear but 20% for women with histiocytes and additional clinical/or Pap smear findings. CONCLUSION: Based on the findings of this study and recently published data, we conclude that the isolated finding of increased histiocytes in the absence of postmenopausal bleeding, endometrial cells or atypical glandular cells on a Pap smear is a poor indicator of uterine disease.     

O-10THE ACCURACY OF CERVICAL CYTOLOGY: A COMPARISON BETWEEN THE THINPREP IMAGING SYSTEM AND CONVENTIONAL METHODS

Douglass Hanly Moir is a large Australian laboratory which has recently introduced the ThinPrep Imaging System (TPI) for reading ThinPrep slides, which is still performed using a split-sample technique. The Imager is a computerized system which identifies 22 fields for the cytologist to review using automated light microscopy. We compared the accuracy of TPI and conventional cytology (CC) during normal laboratory operation. The ThinPrep sample was prepared after taking a conventional Pap smear. TPI and CC reading was done without knowledge of the result of the other reading. The final cytology report issued to the referring doctor reflected the more severe of these two results. Histology results for all cases in which TPI and CC cytology results showed more than minimal disagreement were sought from the NSW Pap Test Register. Of 55 164 split sample pairs, 3.1% of CC of slides and 1.8% of TPI slides were unsatisfactory. There were 1758 women for whom there was more than minimal discrepancy between TPI and CC cytology results. TPI gave the more severe result in 1193 of the 1758 cases. In cases where only one of each pair of discrepant cytology results was CIN1 or higher grade, TPI detected 133 cases of high-grade histology among 380 biopsies (35%), whereas CC detected 62 cases among 210 biopsies (29.5%). A repeat analysis based on reading of histology by one pathologist blinded to initial Pap smear result showed a similar result. Reading times were measured over 5 months for both TPI and CC for twenty cytologists who read both types of smears. On average, they read 13.3 TPI slides per hour and 6.1 CC slides per hour. This study provides evidence that cervical cytology read using the TPI detects more histological high-grade disease than does CC. Further evidence shows that reading times are significantly reduced for cytologists using the TPI.     

Performance of cytology and colposcopy in diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-positive and HIV-negative women

As part of an extensive multi-institutional DIANAIDS-HIV-HPV-SIL project run in Italy (co-ordinated by ISS), the present study compares the performance (sensitivity, specificity, agreement) of routine cervical smear cytology with that of colposcopy in the detection of histologically-confirmed CIN lesions in 37 HIV-positive and 21 HIV-negative women, belonging to the DIANAIDS cohort of 459 women. All women were subjected to a cervical smear, colposcopy and biopsy, making possible the pairwise comparison of these techniques. In the whole series of HIV-positive and HIV-negative women, cytology had a sensitivity of 86.9% and specificity of 83.3%, the sensitivity of grade 2 abnormality on colposcopy against histology being 82.6% and specificity, 33.3%. No statistically significant difference was observed in the performance of Pap smears between the HIV-positive and HIV-negative women. The sensitivity of cytology was 89.7% vs 82.4% and the specificity, 75% vs 100%. For colposcopy, the sensitivity was 79.3% vs 88.2% and the specificity, 75% vs 50%. These data suggest that cervical Pap smear cytology is a highly sensitive and specific diagnostic tool in the clinical monitoring of lower genital tract pathology in HIV-positive women. Colposcopy, on the other hand, proved to be a somewhat less accurate diagnostic tool in these women.     

Evaluation of p16INK4a in cervical lesion of premenopausal and postmenopausal women

Pap smears of postmenopausal women are often misdiagnosed because of the difficulty in distinguishing atrophic epithelial cells groups only by morphological criteria. In this study we investigated the diagnostic application of immunocytochemical staining of p16INK4a on conventional Pap smear. A total of 137 cervical specimens were enrolled in this study, of which 77 and 60 cervical smears were taken from premenopausal and postmenopausal women, respectively. Two cervical smears were taken simultaneously in 68 women, one for conventional cytology and the other for immunostaining. Additional 69 cervical smears were taken from the archive, decolorized and then used for immunostaining. In premenopausal women 1 out of 14 (7.1%) with negative cytology, 7 out of 24 (29.2%) with low grade squamous intra-epithelial lesion (LSIL), all 35 (100%) with high grade squamous intraepithelial lesion (HSIL) and all 4 (100%) with squamous cell carcinoma (confirmed by histopathology) had positive staining to p16INK4a. In postmenopausal women p16INK4a positivity was observed in 4 out of 7 (57.1%) cases of LSIL, 12 out of 14 (85.7%) cases of HSIL and all 4 out of 5 (80%) different cases of carcinoma (1 cervical adenosquamous carcinoma and 3 cervical squamous cell carcinoma in situ confirmed by histopathology), but none of 34 smears with normal cytology. Twenty smears with normal cytology chosen for the negative control in this study were from the group of postmenopausal women and were as expected negative for p16INK4a immunostaining. In the group of postmenopausal women, 16 out of 60 (26.7%) cases the cytological diagnosis was established on the basis of pl6lNK4a immunostaining as being HSIL. From our preliminary study on a limited number of samples, we can however conclude that pl6INK4a immunostaining is a very useful tool for cytological diagnosis enabling to distinguish HSIL from normal, reactive or inflammatory changes.     

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.     

Expert consultation for cervical carcinoma smears. Reliability of selected-field videomicroscopy

OBJECTIVE: To evaluate the diagnostic accuracy of videomicroscopy image selection for expert consultation in cervical cytology. STUDY DESIGN: One hundred diagnostically difficult cervical cytologic smears were selected and rescreened by a general pathologist who chose, from each slide, four or five fields featuring abnormal cells. Video images were digitized and stored on a 512 x 512-pixel matrix using an image acquisition and transmission system. Five experts each reviewed 20 of the 100 cases, and a sixth reviewed all 100 cases. Diagnoses based on selected digitized images were compared to those based on conventional examination of whole slides. RESULTS: Intraobserver agreement was fair to excellent for all six experts (kappa value: 0.47-0.81); it was complete or acceptable in 68.4-85% of cases. Compared to the reference diagnosis, interobserver agreement was not significantly different whether cases were examined by screening the entire slide or by videomicroscopy of selected fields. The marked discordance in four cases concerned very small cells the significance of which was misinterpreted on videomicroscopy because of poor image quality due to lack of focus setting. CONCLUSION: This exploratory study showed that selection of videomicroscopy images seems as reliable as conventional examination of slides for expert consultation on diagnostically difficult cervical cytologic smear cases.     

Quality control in cervicovaginal cytology by cytohistological correlation

N. Izadi‐Mood, S. Sarmadi and S. Sanii
Quality control in cervicovaginal cytology by cytohistological correlation Objective: Frequent studies attest to the correlation of cytological interpretations with defined histopathological entities. Nevertheless, as part of quality control, cytology laboratories are required to compare Papanicolaou smear reports with those of cervical biopsies to search for discrepancies. We have attempted to determine and categorize the causes of existing discrepancies in our laboratory in order to clarify the source of errors. Methods: We reviewed 670 cervical smears that were paired with subsequent punch biopsy or endocervical curettage samples, obtained within 2 months of the cytology, and found out that 60 smear‐biopsy pairs were discrepant regarding the diagnosis. These cases were categorized into four error groups after careful re‐evaluation of the original smear and biopsy slides. Results: In 51 (85%) of 60 cervical smear‐biopsy pairs with reports that disagreed, the initial diagnoses of both cervical smear and biopsy were confirmed by the review opinion; in these cases, cytology and biopsy ‘sampling errors’ were responsible for 40 and 11 instances of discrepancy, respectively. Seven cases (11.1%) were discrepant due to ‘smear interpretation errors’ and consisted of five cases with initial under‐diagnosis and two cases with initial over‐diagnosis. One case (1.7%) was due to ‘screener error’. In another case, discordance was due to cervical ‘biopsy interpretation error’, with initial over‐diagnosis as squamous intraepithelial lesion. Conclusion: In this retrospective study, we determined the causes of cytohistological discrepancies in cervical samples. The main explanation for discrepancy was ‘sampling error’.     

Conventional Pap smear and liquid-based cytology as screening tools in low-resource settings in Latin America: experience of the Latin American screening study

OBJECTIVE: To evaluate the performance of the conventional Pap test and liquid-based cytology (LBC) in an ongoing multicenter trial testing optional screening tools (cytology, screening colposcopy, visual inspection with acetic acid, visual inspection with Lugol's Iodine, cervicography and Hybrid Capture II [HCII] (Digene Brazil, S?o Paulo, Brazil) conventional and self-sampling), for cervical cancer in Brazil and Argentina. STUDY DESIGN: A cohort of 12,107 women attending four clinics (Campinas, S?o Paulo, Porto Alegre, Buenos Aires) were randomized into the 8 diagnostic arms. Women testing positive with any of the tests were referred for colposcopy, and cervical biopsies were used as the gold standard to assess performance characteristics of the diagnostic tests. Conventional Pap smears were sampled by all clinics (n = 10,240), and LBC (Autocyte PREP, [TriPath Imaging, Burlington, North Carolina, U.S.A.], n=320, and DNA-Citoliq [Digene Brazil], n =1,346) was performed by 1 of the clinics. RESULTS: Conventional Pap smears showed no squamous intraepithelial lesions (normal) in 8,946 (87.4%) and LBC in 1,373 (82.4%). Using high grade squamous intraepithelial lesions (HSIL) as the cutoff, Pap smears predicted high grade (cervical intraepithelial neoplasia [CIN] 3) with OR 63.0 (95% CI, 36.90-107.70), standard error (SE) 59%, SP 97.8%, positive predictive value (PPV) 68.1% and negative predictive value (NPV) 96.7%. The same figures for Autocyte PREP were: OR 9.0 (95% CI, 2.43-33.24), sensitivity (SE) 33.3%, specificity (SP) 100%, PPV 100% and negative PV (NPV) 88.8%. DNA-Citoliq detected CIN 3 as follows: OR 11.8 (95% CI 2.60-53.26), SE 40.0%, SP 94.6%, PPV 40.0% and NPV 94.6%. Lowering the cutoff to low grade squamous intraepithelial lesions increased SE and NPV but compromised SP and PPV. The detection rates for high grade lesions after an atypical squamous cells of undetermined significance diagnosis were similar with the 3 techniques. In our settings, the 3 methods of cervical cytology were slightly different in performance. The conventional Pap smear had the highest SE, while Autocyte PREP had 100% SP and PPV in detecting CIN3 with the HSIL cutoff. All 3 tests had lower SE but higher SP as compared to HCII.     

Education and training for cytopathologists. Its role in quality assurance

The role of education and training for cytopathologists in assuring quality in cytology laboratories is discussed, with particular attention given to (1) the problems in the diagnosis of Papanicolaou smears and (2) the contributions of the American Society of Cytology to cytology education. While many people contribute to the success or failure of gynecologic screening programs, poorly trained pathologists can be an especially weak link in the chain given their position in the diagnostic process. Well-formulated residency programs and the use of other educational resources can produce higher-caliber cytopathologists. The problems in Papanicolaou smear screening need to be defined, discussed and resolved by well-trained cytopathologists in conjunction with the clinicians and cytotechnologists involved.