Direct-to-vial comparison of a new liquid-based cytology system, liqui-PREP versus the conventional pap smear

The objective of the study was to assess the clinical utility of a liquid-based cytology system on cervicovaginal screening in a clinical commercial laboratory. Twenty-six thousand, one hundred and seventy eight cervicovaginal specimens were prepared by the Liqui-PREP (LGM International Inc., Ft. Lauderdale, FL) with a direct-to-vial comparison to 218,548 cases of the conventional direct smear from August 2005 through December 2005. Biopsy data was obtained to confirm the sensitivity for each method. Liqui-PREP showed a marked increase in HSIL+ detection compared to the conventional smear ( P = 0.001). The rate of LSIL and AGC detection was higher with Liqui-PREP ( P equals; 0.001 for both). The percentage of ASCUS specimens was higher than with conventional smear due to cleaner slides and easier detection of suspicious cells. The WNL rate was lower for Liqui- PREP ( P = 0.001) consistent with increased HSIL+ and ASCUS. The unsatisfactory rate was lower for Liqui-PREP ( P = 0.017). The histological predictive value of Liqui-PREP was slightly higher than the conventional smear (94.1% versus 89.9%). The Liqui-PREP system similar to other reported LBC technologies shows an increased detection of squamous intraepithelial lesions, and gives higher-quality slides for interpretation than the conventional smear. Histological results confirm that this increase in cytological findings are clinically significant. LGM's new LBC technology is a more sensitive screening tool when compared with the conventional smear.     

Comparison of conventional Papanicolaou cytology samples with liquid-based cervical cytology samples from women in Pernambuco, Brazil

In the present study, we compared the performance of a ThinPrep cytological methodwith the conventional Papanicolaou test for diagnosis of cytopathological changes,with regard to unsatisfactory results achieved at the Central Public HealthLaboratory of the State of Pernambuco. A population-based, cross-sectional study wasperformed with women aged 18 to 65 years, who spontaneously sought gynecologicalservices in Public Health Units in the State of Pernambuco, Northeast Brazil, betweenApril and November 2011. All patients in the study were given a standardizedquestionnaire on sociodemographics, sexual characteristics, reproductive practices,and habits. A total of 525 patients were assessed by the two methods (11.05% wereunder the age of 25 years, 30.86% were single, 4.4% had had more than 5 sexualpartners, 44% were not using contraception, 38.85% were users of alcohol, 24.38% weresmokers, 3.24% had consumed drugs previously, 42.01% had gynecological complaints,and 12.19% had an early history of sexually transmitted diseases). The two methodsshowed poor correlation (k=0.19; 95%CI=0.11–0.26; P<0.001). TheThinPrep method reduced the rate of unsatisfactory results from 4.38% to 1.71%(χ²=5.28; P=0.02), and the number of cytopathological changes diagnosedincreased from 2.47% to 3.04%. This study confirmed that adopting the ThinPrep methodfor diagnosis of cervical cytological samples was an improvement over theconventional method. Furthermore, this method may reduce possible losses fromcytological resampling and reduce obstacles to patient follow-up, improving thequality of the public health system in the State of Pernambuco, Northeast Brazil.     

Conventional and liquid-based cervicovaginal cytology: a comparison study with clinical and histologic follow-up

Increased rates of squamous intraepithelial lesion (SIL) diagnosis with liquid-based cervicovaginal cytology (CVC) methods are well documented. This retrospective study compares the ability of the ThinPrep Pap Test (TP) and the conventional Pap smear (CP) to detect biopsy-proven SIL and to exclude nonneoplastic disease. All CVC reports from January 1999 through December 2000 from seven community Family Medicine clinics affiliated with the University of Nebraska were reviewed. For women with at least one CVC diagnosis of epithelial cell abnormality (ECA), follow-up histology, cytology, and clinical data were obtained. Statistical analysis was performed using the chi-square method. SIL was diagnosed in 166 of 3,286 patients by TP (5.1%) and in 169 of 4,872 patients by CP (3.5%) (P < 0.001); 32 of the TP diagnoses (1.0%) and 34 of the CP diagnoses (0.7%) were high-grade SIL (HSIL). Atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) was the most severe abnormality diagnosed by TP in 218 patients (6.6%) and by CP in 279 patients (5.7%). Follow-up histology data on CVC SIL diagnoses showed evidence of cervical intraepithelial neoplasia in 94 patients screened by TP (2.9%) and in 79 patients screened by CP (1.6%) (P < 0.001); the biopsy diagnoses were CIN 2 or CIN 3 in 34 patients in the TP group (1.0%) and in 28 patients in the CP group (0.6%) (P < 0.025). Follow-up of patients in whom the first ECA CVC diagnosis was ASCUS or AGUS disclosed a positive predictive value for CIN of 22.8% for TP ASCUS/AGUS diagnoses and 11.9% for CP ASCUS/AGUS diagnoses (P < 0.005). In this population, TP was significantly better than CP in detecting biopsy- proven disease and in screening out benign abnormalities.     

Comparison of conventional Papanicolaou smears and fluid-based, thin-layer cytology with colposcopic biopsy control in central Italy: a consecutive sampling study of 461 cases

The aim of this study was to compare the cytologic diagnosis and specimen adequacy of conventional Papanicolaou (CP) and fluid-based, thin-layer [ThinPrep (TP), Cytyc, Boxborough, MA] cervical cytology in a population from central Italy. CP and TP samples were collected simultaneously using a consecutive sampling method on women presenting for cervical screening. Colposcopy was performed as clinically indicated, and biopsy results were compared with cytologic diagnoses. Among the 461 patients included in the study, 413 were negative at both CP and TP, 9 had unsatisfactory results at both tests and 39 patients presented abnormal results at CP, TP or both. Cohen's Kappa was 0.77 showing good agreement between CP and TP test results. Histological data were available for 20 (51.28%) of the 39 patients with at least one positive test. Among the 13 patients with HSIL at histology, 7 had HSIL at CP (sensitivity 53.85%) and 5 at TP (sensitivity 38.46%). For all three patients with squamous cell carcinoma (SCC) at histology, CP and TP had shown the same diagnosis (sensitivity 100%). The positive predictive values were 33.33% for CP and 25.0% for TP regarding the LSIL diagnosis and 100% for both CP and TP regarding HSIL and SCC diagnoses. Our results may be influenced by the consecutive sampling procedure.     

Testing automated liquid-based cytology samples with a manual liquid-based cytology method using residual cell suspensions from 500 ThinPrep cases

We report a technical improvement upon a previously disclosed manual liquid-based cytology (MLBC) method; and, we use the improved method to prepare slides from residual ThinPrep specimens in order to see how often ThinPrep diagnoses correspond to diagnoses derived from exhaustive examination of their parent sample suspensions. Residual cell suspensions from 500 ThinPrep cases comprising (1) 20 low-grade squamous intraepithelial lesions (LSILs); (2) 200 high risk (HR) negatives and 20 ASC-US; and (3) 260 screening cytology specimens were studied. Institutional review committee guidelines allowed us to know diagnoses by groups of specimens, but did not allow us to know individual patient diagnoses, so we could not perform case-by-case matched outcome-comparisons. Cells were concentrated by conventional centrifugation and sedimented into a polymer gel that was then vortex-mixed and converted into a viscous cell-rich suspension. The cell suspension was smeared between two clean glass slides, which were air-dried and stained with the Papanicolaou stain. Two study-sets were created, comprising one slide from each case. Each of the two study sets was examined by two cytopathologists, and discordant diagnoses were adjudicated. Because of the ambiguity involved in the "atypical" (ASC-US, ASC-H, AGC) diagnosis categories, only outcomes at the level of LSIL or greater were recorded. All MLBC SILs were digitally imaged and abnormal slides plus digital images were sent to the laboratory that provided the residual automated liquid-based cytology (ALBC) suspensions. The final diagnoses were confirmed by the laboratory that provided the residual ALBC specimens. MLBC slides of the 20 LSIL cases afforded 2 high-grade squamous intraepithelial lesions (HSILs) and 18 LSILs. Those of the 200 HR-Negatives showed 3 HSILs and 30 LSILs; and those of the 20 HR-ASC-US showed 3 HSILs and 9 LSILs. MLBC slides of the 260 screening cytology specimens showed 1 Carcinoma, 3 HSILs and 20 LSILs; affording 3 HSILs and 14 LSILs more than originally diagnosed. The MLBC method of this report is useful for preparing cell suspensions for cytological examination. Our analytical method was exhaustive and used nearly all of the cell material that was provided to us for analysis; therefore, we conclude that this approach is useful for determining how well ALBC instruments represent their parent sample suspensions. It appears that "rare events" may be overlooked when limited sample aliquots are analyzed by ALBC instruments, and this probably accounts for our increased discovery of SILs by the MLBC method. Also, SILs often present as aggregates of cohesive cells which, if overlooked or ineffectively transferred to ALBC slides, would not be diagnosed.     

Non-gynecologic cytology on liquid-based preparations: A morphologic review of facts and artifacts

Liquid-based preparations (LBP) are increasingly being used both for gynecologic (gyn) and non-gynecologic (non-gyn) cytology including fine needle aspirations (FNA). The two FDA-approved LBP currently in use include ThinPrep (TP), (Cytyc Corp, Marlborough, MA) and SurePath (SP), (TriPath Imaging Inc., Burlington, NC). TP was approved for cervico-vaginal (Pap test) cytology in 1996 and SP in 1999 and both have since also been used for non-gyn cytology. In the LBP, instead of being smeared, cells are rinsed into a liquid preservative collection medium and processed on automated devices. Even after a decade of use, the morphological interpretation of LBP remains a diagnostic challenge because of somewhat altered morphology and artifacts or facts resulting from the fixation and processing techniques. These changes include cleaner background with altered or reduced background and extracellular elements; architectural changes such as smaller cell clusters and sheets, breakage of papillae; altered cell distribution with more dyscohesion and changes in cellular morphology with enhanced nuclear features, smaller cell size and slightly more three-dimensional (3-D) clusters. Herein, we review the published literature on morphological aspects of LBP for non-gyn cytology.     

Morphometric image analysis of pancreatic disease by ThinPrep liquid-based cytology

Liquid‐based cytology preparations are being increasingly used in nongynecologic specimens. The aim of this study is to objectively evaluate pancreatic disease by ThinPrep (TP) liquid‐based cytology using morphometric image analysis. In all, 30 patients undergoing preoperative evaluation of pancreatic disease by TP were investigated from January to April 2009. We analyzed cytological features, such as cluster area, cluster circularity, and nucleus area, using morphometric image analysis software and further investigated the cytological findings of TP to determine which are useful for detecting malignancy. Pancreatic cytological findings of TP showed small clusters and loss of cluster irregularity in malignant cells. The patients were diagnostically categorized as inadequate, normal or benign, indeterminate, suspected malignancy, and malignant in 6.6% (2), 46.7% (14), 13.3% (4), 13.3% (4), and 20.0% (6) of the cases, respectively. Morphometric image analysis of 28 patients by TP,excluding two inadequate patients, showed no statistical difference in cluster area or cluster circularity among these cytological categories. In contrast, nucleus area in the normal or benign, indeterminate, suspected malignancy, and malignant categories was 17.6, 57.2, 67.4, and 68.0 μm², respectively, and was associated with diagnostic category (P < 0.05). Pancreatic cytological findings of TP preparations generally show small, round cluster shapes in pancreatic disease; however, nucleus size is a more important criteria for detecting malignancy by TP in pancreatic disease. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.     

The significance of endocervical cells and metaplastic squamous cells in liquid‐based cervical cytology

We conducted a retrospective study to investigate whether the presence or absence of endocervical cells (EC) and metaplastic squamous cells (MSC) was associated with the detection of squamous intraepithelial lesions in liquid‐based cervical cytology. 90,376 cases of liquid‐based cervical cytology smears received in 2006 were included in the study. Low‐grade (LSIL) and high‐grade squamous intraepithelial lesions (HSIL) were classified according to the Bethesda system (2001). The rates of detecting LSIL and HSIL in smears with and without EC and/or MSC were determined. There were 1,540 LSIL and 396 HSIL. The ratio of HSIL/NILM (no intraepithelial lesion or malignancy) was 0.0022 in smears without EC or MSC, 0.0040 in smears with EC only, 0.0044 in smears with MSC only, and 0.0056 in smears with both EC and MSC present. Compared with smears without EC or MSC, this ratio was significantly higher (P < 0.05) when either EC or MSC was present. Compared with smears with EC only, the ratio was also significantly higher when both EC and MSC were present (P < 0.05). On the other hand, the presence or absence of EC had no effect on the detection rate of LSIL (0.0191 for both groups), while the presence of MSC was actually associated with lower detection rate of LSIL (0.0153, P < 0.05). The presence of endocervical and metaplastic cells was associated with higher detection rates of HSIL. MSC was associated with lower detection or LSIL. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Dutch solutions for liquid-based cytology: analysis of unsatisfactory slides and HPV testing of equivocal cytology

The liquid-based techniques to obtain microscopy slides for cervical screening have replaced conventional smears almost completely in the USA, but not in all European countries. The decision making process to use liquid-based cytology (LBC) for nationwide screening programs depends on the health system. In a pilot study of over 7,000 screenees, we analyzed the unsatisfactory LBC slides and tested the equivocal cytologies for HPV by using the LiPA test. For comparison over 48,000 conventional screening data were used. Compared to conventional smears, the LBC slides were highly cellular, the state of fixation was much better, and obscuring blood did not exist. The unsatisfactory rate showed an increase from 262/100,000 (conventional smears) to 357/100,000 (LBC slides) due to too thick, undiagnosable epithelial fragments on the LBC slides. HPV testing of the equivocal cytology leads to a better patient management and less unnecessary referrals.     

Cervical biopsy-based comparison of a new liquid-based thin-layer preparation with conventional Pap smears

The objective of this study is to compare the diagnostic efficacy of universal collection medium (UCM) liquid-based cytology (LBC) (Digene Corp., MD) and the conventional Pap smear in a comparative study, using histologic results as the gold standard. This was a cross-sectional study. Conventional Pap smears and UCM LBC specimens, obtained from women in a low socioeconomic outpatient population referred to a tertiary center for gynecologic care, were compared. For the purpose of this study, when cervical specimens were collected for cytology, all women underwent colposcopy and biopsy was done if a cervical abnormality was observed. Cytologic evaluation of UCM LBC and conventional Pap smears were carried out separately, masked to the results of the other method. Agreement beyond chance between the two cytologic methods was ascertained by means of the unweighted kappa statistic. Sensitivity, specificity, and predictive values with 95% confidence intervals were calculated for both methods. McNemar's test was used to determine the level of association between the two cytology procedures. A total of 800 women were evaluated. Assessment of the overall agreement between the two cytologic methods yielded a kappa of 0.777 (P < 0.0001). After adjustment for histologic diagnosis, the computed kappa in each stratum was as follows: normal = 0.733; CIN 1 = 0.631; CIN 2/3 = 0.735; cancer = 0.652. The sensitivity and specificity of UCM LBC for detection of cervical intraepithelial lesions and cancer were 75.3% and 86.4%, respectively, not statistically different from the 81.8% and 85.2% seen with the conventional method. This study demonstrates that the UCM LBC method is as accurate as the conventional Pap smear cytology in detecting cervical intraepithelial lesions and cancer even so the UCM samples were systematically prepared from a second sampling of the cervix.     

Evaluation of agreement between conventional and liquid-based cytology in cervical cancer early detection based on analysis of 2,091 smears: experience at the Brazilian National Cancer Institute

The aim of this work was to evaluate the agreement between conventional cytology (CC) and liquid-based cytology (LBC) in cervical cancer early detection.The results of CC and LBC (DNACitoliq in 2,059 women aged 25-59 years were compared. The percent agreement, kappa coefficient, prevalence-adjusted bias-adjusted kappa coefficient (PABAK), and Chamberlain's percent positive agreement (PPA) were calculated.The percent agreement between the two methods was very good (80% and 79%, respectively, for normal versus ASCUS+; and normal versus ASCUS, AGUS and LSIL+ vs. HSIL+). The kappa coefficient indicates slight agreement (0.26 and 0.23, respectively), but when PABAK was used the agreement was good (0.61 and 0.68, respectively). PPA was high for normal results (79.2%) and low for the remaining categories.To conclude, in this study, agreement between LBC and CC was only good for normal results, which involves the majority of cases and positively influences the overall agreement rate.     

Automated screening versus manual screening: a comparison of the ThinPrep imaging system and manual screening in a time study

The ThinPrep Imaging System (TIS) is an automated system that assists cytotechnologists in the primary screening of ThinPrep liquid based cervical samples. Between June 1, 2004, and April 1, 2005, four experienced cytotechnologists participated in the study in which the duration of the screening procedure was timed for each of the 11,354 slides included. In every slide 22 fields of view were reviewed, and the samples that contained potentially abnormal cells were fully screened. The screening time was reduced by 42% (mean) (p < 0.001). By manual rescreening of the negative TIS samples, abnormal cells were found in 10 samples (false negative rate 0.14%). In every case the abnormal cells had been identified by the scanner, but misinterpreted by the cytotechnologist. These findings stressed the importance of carefulness in the interpretation of the marked fields and beyond that helped the cytotechnologists and pathologists to have more confidence in the automated system.     

Resolving ASCUS without recourse to HPV testing: manual reprocessing of residual automated liquid-based cytology (ALBC) material using manual liquid-based cytology (MLBC)

We show that residual cell material from ThinPrep PapTest (Cytyc Corporation, Boxborough, MA) atypical squamous-cells of undetermined significance (ASCUS) cases may be manually reprocessed to triage women into actionable diagnostic categories (HSIL, LSIL, and Negative). Material remaining from each of 358 ThinPrep ASCUS cases was manually reprocessed as two slides, labeled "A" and "B." Interobserver agreement between case contributors (CCs) and three sequential reviewers (SRs) was analyzed with 186 cases (Study 1), and diagnostic reproducibility between SRs was examined with an additional 172 cases (Study 2). In Study 1, CCs classified 33% of cases as LSIL or greater, SRs classified 60% as LSIL or greater, and there was 58% diagnostic agreement between CCs and SRs. No "Negative" case assignment by one group afforded an "HSIL" assignment by the complementary group. In Study 2, there was 95% agreement between SRs A slide and B slide diagnoses with 54% of A slides and 55% of B slides classified as LISL or greater. Again, no "Negative" case assignment to one slide afforded an "HSIL" assignment to the complementary slide. Overall, 12.6% of the 358 cases showed HSIL, and all HSILs by one observer group were ASCUS or greater by the complementary observer group. Using manual reprocessing beyond the 21-day specimen outdate for HPV testing by the Hybrid Capture II High Risk HPV test (HR-HCII; Digene Corporation, Beltsville, MD), many ThinPrep ASCUS cases were reclassified as LSIL or HSIL. The 12.6% HSIL proportion of this study approximated the 11.5% CIN 2 or greater proportion of the ALTS ASCUS arm. Similar to ALTS, manual liquid-based cytology (MLBC) would have referred nearly 60% of women to colposcopy for a definitive diagnosis of HSIL or LSIL without resorting to HPV testing. These data demonstrate that many cases of automated liquid-based cytology (ALBC)-diagnosed ASCUS represent unrecognized SIL, which is present in the ALBC specimen vial at the time the ASCUS diagnosis is rendered.     

Liqui‐PREP® versus conventional papanicolaou smear to detect cervical cells abnormality by split‐sample technique: A randomized double‐blind controlled trial

To assess the diagnostic performances of LiquiPrep® (LP) to detect cervical cellular abnormality in comparison to Papanicolaou (Pap) smear in 194 women with abnormal cervical cytology who were scheduled for colposcopy at the institution between January 2008 and November 2008. The women were randomized to undergo a repeated cervical cytologic evaluation by Pap smear followed by LP, or the two methods in alternating order. The pathologist was blinded to previous cytologic diagnosis and the pair of slides assigned for each woman. Cytologic results from each method were compared to subsequent histopathology. Mean screening time for each LP and Pap slides were 4.3 ± 1.2 minutes and 5.4 ± 1.1 minutes, respectively (P < 0.001). From 194 cases, ASC or AGC were diagnosed in 72 cases (37.1%) from LP and 68 cases (35.1%) from Pap smear. After excluding the ASC/AGC group, the overall cytologic diagnostic agreement between the two tests were 69 of 87 cases (73.6%) while the agreements with histologic diagnoses were 39/87 cases from LP (44.8%) and 41 (47.1%) from Pap smear (P = 0.824). The accuracy of LP was not significantly different from Pap test, 43.4% (95% confidence interval [CI]: 34.8–52.1%) compared to 44.4% (95% CI: 35.7–53.1%). LP did not have superior performance over Pap test to detect high‐grade lesions (≥cervical intraepithelial neoplasia II) using ASC/AGC as the threshold with the sensitivity of 70.5% (95% CI: 64.0–76.9%) versus 77.3% (95% CI: 71.4–83.2%), respectively. Diagn. Cytopathol. 2011;39:22–27. © 2010 Wiley‐Liss, Inc.     

Comparative image analysis of conventional and thin‐layer preparations in endometrial cytology

We evaluated the differences in cytologic findings between conventional and thin‐layer preparations in endometrial cytology to introduce the thin‐layer method into routine cytology. Eighty patients who had undergone endometrial cytology and biopsy on the same day were selected and we compared the cytological findings between conventional‐ and thin‐layer preparations (TLP) in endometrial cytology. The numbers of neutrophils and cell clusters in the thin‐layer method were lower than those in the conventional smear (CSS) method. The average number of neutrophils in endometrioid adenocarcinoma was significantly higher than that in normal morphology endometrium and endometrial hyperplasia. Regarding the shape of the cell clusters, ball‐like patterns and round‐edged cell clusters were not identified in CSS. The average number of clusters in CSS was significantly greater than that using the TLP. The average of the nuclear area in CSS was significantly larger than that using the TLP, indicating that the nuclear areas in CSS were more uneven than that using the TLP. In the future, it is expected that liquid‐based cytology will be applied to the cytological diagnosis of a variety of lesions. The influence on cells due to fixation is considerable in liquid‐based preparations. Therefore, if we strive to pick up the differences between CSS and TLP of endometrial samples, the diagnostic accuracy of the latter could be improved. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Vaginal Enterobius vermicularis diagnosed on liquid‐based cytology during Papanicolaou test cervical cancer screening: A report of two cases and a review of the literature

Enterobiasis is one of the most common human parasitic infections. It is considered an intestinal parasite, but cases of extra‐intestinal affections exist, notably infections of the female genital tract. Enterobius vermicularis (EV) eggs (or ova) have been found in the cervical smears of two patients in our institute during the last 16 years. No gynaecological or gastrointestinal symptoms were reported, and there was no known intestinal infection in these two cases. A review of the available literature revealed rare cases of vaginal enterobiasis, with a wide range of clinical presentations, many patients being asymptomatic. The diagnosis may sometimes be difficult, mainly because of the lack of clinical suspicion. However, cytological identification of EV in cervico‐vaginal smears is important, especially when considering the risk of ascending infections of the genital tract associated with severe complications.