Comparison of the SurePath liquid-based Papanicolaou smear with the conventional Papanicolaou smear in a multisite direct-to-vial study

BACKGROUND: Split-sample clinical trials for liquid-based Papanicolaou (Pap) smears demonstrated that the liquid-based Pap smear was a safe and effective replacement for the conventional Pap smear. However, clinical intended use of liquid-based technology employs direct-to-vial collection methods. The current study compared the cytologic detection rates of the liquid-based Pap smear with conventional Pap smears in a direct-to-vial study performed at three clinical sites. METHODS: Data from 58,580 prospective SurePath slides and 58,988 historic conventional slides were collected. Results were statistically compared with regard to disease prevalence and adequacy to include biopsy follow-up data for conventional and SurePath tests. RESULTS: The SurePath method was found to provide a statistically significantly greater detection rate for clinically important categories of high-grade squamous intraepithelial lesion (HSIL+) and low-grade squamous intraepithelial lesion (LSIL+) (64% and 107%, respectively; P < 0.00001 for each lesion) compared with conventional slides. The clinical significance of increased cytologic detection using SurePath was supported by biopsy data that essentially demonstrated concordance with regard to biopsy interpretation for HSIL+ (P = 0.9105 at Site 1; P = 1.0000 at Site 2; and P = 1.0000 at Site 3) and LSIL+ (P = 0.6966 at Site 1; P = 0.8052 at Site 2; and P = 1.00 at Site 3). The detection rate of atypical squamous cells of undetermined significance (ASCUS+) was found to be significantly increased (75.12%; P < 0.00001). A statistically significantly lower proportion of unsatisfactory slides using the SurePath test compared with conventional slides was noted (-58%; P < 0.00001). The ASCUS/LSIL+ ratio was found to be reduced overall when using SurePath (-28.9%), regardless of whether the study sites were combined or considered individually. The rate of false-negative results noted with SurePath (10.43%) and conventional slides (12.97%) was essentially equivalent. CONCLUSIONS: The SurePath Pap smear was found to outperform conventional slides in the detection of HSIL+ and LSIL+ cytologic lesions of the cervix and reduced the number of unsatisfactory diagnoses. The HSIL+ advantage for SurePath is not limited to HSIL but appears to extend to carcinoma as well.     

Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma

BACKGROUND: In a study using a split-sample design, liquid-based cytology (ThinPrep Processor, Cytyc Corporation, Boxborough, MA) was compared with the conventional Papanicolaou (Pap) smear in Guanacaste, Costa Rica. The study provides the first population-based comparison of the ThinPrep screening technology and includes "gold standard" measures of diagnostic accuracy. METHODS: The population-based study was performed among over 8000 women residing in a Costa Rican province with a high incidence of cervical carcinoma. Conventional smears were prepared and diagnosed in Costa Rica, while the residual material on the sampling device was collected into a liquid preservative and shipped to the U.S., where ThinPrep cytologic slides were prepared and diagnosed. Cytologic diagnoses based on the two techniques, categorized according to the Bethesda System, were compared with a "gold standard" final case diagnosis for each patient, also based on Bethesda terminology, that reflected an integrated interpretation of all available data, including cytology, histology, and cervicography. Results were also compared with the results of HPV DNA detection (Hybrid Capture, Digene Corporation, Silver Spring, MD). RESULTS: ASCUS was the threshold for colposcopy referral. There were significantly more women referred according to this threshold with the ThinPrep slide (12.7%) than with the conventional smear (6.7%, P<0.001). Compared with the final case diagnosis, referral by ThinPrep slides detected 92.9% of cases with high grade squamous intraepithelial lesions (HSIL) and 100% of carcinoma cases. Smears detected 77.8% of HSIL and 90.9% of carcinomas. Thus, ThinPrep cytology was significantly more sensitive in the detection of HSIL and cancer (McNemar test, P<0.001). Adjudication of cases in which the ThinPrep and smear diagnoses disagreed, using the final case diagnoses and the HPV DNA test results as reference standards, suggested that the ThinPrep method was detecting additional true SIL as opposed to false-positives. CONCLUSIONS: In a population-based study of high risk women, ThinPrep cytology demonstrated significantly increased sensitivity for detecting HSIL and carcinoma, with a concurrent significant increase in colposcopy referrals.     

Oral contraceptive pills are associated with artifacts in ThinPrep Pap smears that mimic low-grade squamous intraepithelial lesions

BACKGROUND: The authors noted a significant increase in the diagnosis of atypical squamous cells of undetermined significance (ASCUS) in premenopausal women using oral contraceptive pills (OCP) (9%) versus women not on OCP (4%) using ThinPrep Pap smears (P = 0.02). The purpose of this study was to correlate these morphologic changes with human papillomavirus (HPV) DNA detection by in situ hybridization and clinical follow-up. METHODS: Eighty-four ThinPrep Pap smears diagnosed as ASCUS or ASCUS favor low-grade squamous intraepithelial lesions (LGSIL) in young women receiving OCP were studied by HPV in situ hybridization. This information was correlated with colposcopic follow-up and AutoCyte Pap smear results. The authors also studied 80 ThinPreps from young women with a Pap smear diagnosis of unequivocal LGSIL where there was a corresponding biopsy (positive controls) and 40 ThinPreps diagnosed as within normal limits and that rescreened as such (negative controls). RESULTS: The detection rate of HPV DNA by in situ hybridization was 33% (28 of 84) in ASCUS cases versus 90% (72 of 80) for cases of unequivocal LGSIL. A blinded review of the 29 ASCUS Pap smears performed by AutoCyte showed that 66% (19 of 29) were diagnosed as within normal limits. The majority of the cervical biopsies in the women with ASCUS by ThinPrep Pap smears were negative for dysplasia (29 of 39 [74%]) whereas 71 of 80 biopsies (88%) showed dysplasia in women with Pap smears diagnosed as unequivocal LGSIL. The periodic acid-Schiff (PAS) stain demonstrated that many of the cells with halos in the ThinPrep Pap smears that mimicked LGSIL contained glycogen. CONCLUSION: The ThinPrep induces changes that mimic LGSIL in young women on OCP. These artifacts may reflect pressure-induced alteration of glycogen. PAS analysis and, more directly, HPV testing by in situ hybridization can help differentiate this mimicking from actual LGSILs.     

Reducing or eliminating use of the category of atypical squamous cells of undetermined significance decreases the diagnostic accuracy of the Papanicolaou smear

BACKGROUND: The diagnosis of "atypical squamous cells of undetermined significance" (ASCUS) is controversial, not only for the clinical utility of its subcategories (favor reactive vs. favor dysplasia), but for its very existence as an expression of uncertainty. In the current study, the authors investigated the impact of reducing and eliminating this category on the sensitivity and predictive values for detecting squamous intraepithelial lesions (SILs).METHODS: One hundred cervical Papanicolaou (Pap) smears originally diagnosed as ASCUS, all of which had histologic follow-up, were reviewed blindly and reclassified as either negative (within normal limits/benign cellular changes), low-grade SIL (LSIL), or high-grade SIL (HSIL) by 1 reviewer who eliminated ASCUS as a diagnostic possibility entirely. A second reviewer reinterpreted the cases but attempted to use the ASCUS diagnosis (favor reactive or favor dysplasia) sparingly. All histologic diagnoses were reviewed, and an adjudicated final diagnosis was established. Reviewed smear interpretations were correlated with the histologic diagnosis (original, reviewed, and adjudicated). Statistical analysis was performed using the Fisher exact test.RESULTS: Thirty-eight women had histologically confirmed SIL (21 LSIL cases and 17 HSIL cases [including 1 case of endocervical adenocarcinoma]); 31 of these 38 cases originally were classified as ASCUS, not otherwise specified, 1 case was classified as ASCUS favor reactive, and 6 cases were classified as ASCUS favor dysplasia. The reviewer who used the ASCUS diagnosis sparingly reclassified the smears as negative (62 cases); ASCUS, favor reactive (3 cases); ASCUS, favor dysplasia (13 cases); LSIL (19 cases); and HSIL (3 cases). The reviewer who eliminated the ASCUS category reclassified the smears as negative (59 cases), LSIL (29 cases), and HSIL (12 cases). The rate of SIL/HSIL in those cases interpreted as abnormal was 38%/17% originally, 42%/24% with a reduced ASCUS interpretation, and 37%/17% when the ASCUS category was eliminated. In those ASCUS smears that were reclassified as negative, the SIL/HSIL rate was 35%/13% with the reduced ASCUS interpretation and 39%/17% when the ASCUS category was eliminated. The sensitivity for detecting a SIL/HSIL was reduced from 100%/100% for the original ASCUS interpretation to 42%/53% for the reduced ASCUS interpretation to 39%/41% with the elimination of the ASCUS interpretation.CONCLUSIONS: Although in the current study utilization of the ASCUS diagnosis was found to result in a 62% negative or reactive outcome on biopsy, a significant number of patients with SIL were detected (38% in the current series, 17% with HSIL). Despite the improved correlation with negative biopsies, reducing or eliminating the ASCUS diagnosis appears to decrease the sensitivity of the Pap smear significantly and appears to be no better than chance at predicting a diagnosis of SIL on biopsy, including HSIL.     

The PapSpin: a reasonable alternative to other, more expensive liquid-based Papanicolaou tests

BACKGROUND: This study was designed to optimize a liquid-based Papanicolaou (Pap) test by using common cytopathology laboratory equipment and resulted in an inexpensive test that was equivalent at least diagnostically to the conventional Papanicolaou (Pap) smear. METHODS: Adult women (n = 482) were consented, enrolled, and included in this Institutional Review Board-approved study. After conventional Pap smear slides were obtained, clinicians placed the collection device with residual cells from the uterine cervix in a preservative fluid. In the cytopathology laboratory, a conventional centrifuge device was used to deposit the cells from the liquid onto a glass slide. RESULTS: Among the conventional Pap smears, 43 were categorized as low-grade squamous intraepithelial lesions (LSIL), and 30 were categorized as high-grade squamous intraepithelial lesions or greater (HSIL+). Among the PapSpin samples, 49 were categorized as LSIL and 24 were categorized as HSIL+. Biopsy confirmation was obtained in 124 patients. There were 23 women diagnosed with LSIL and 27 women diagnosed with HSIL+. Diagnostic agreement between cytologic samples and biopsies is as follows: for conventional Pap smears, there was agreement on 11 of 23 LSIL diagnoses and on 15 of 27 HSIL+ diagnoses; for PapSpin samples, there was agreement on 11 of 23 LSIL diagnoses and on 14 of 27 HSIL+ diagnoses. Exact agreement was achieved between PapSpin and conventional smears in 404 patients (84%). Quality indictors were better in the PapSpin group, except for inadequate endocervical component, which was greater in the PapSpin samples, a difference that was explained by the split-sample study design, which favored the conventional smear. CONCLUSIONS: The current results indicated that PapSpin is a legitimate, inexpensive alternative to the conventional Pap smear for the detection of cervical intraepithelial neoplasia, resulting in better preservation and improved cell visualization. In addition, the liquid residual allows for reflex human papillomavirus-DNA or polymerase chain reaction testing.     

ThinPrep versus conventional Papanicolaou smear in the cytologic follow-up of women with equivocal cervical smears

BACKGROUND: The purpose of the current study was to compare the efficacy of liquid-based cytology and conventional smears in the cytologic follow-up of cases with "atypical squamous cells, cannot exclude a high-grade lesion" (ASC-H) or "atypical glandular cells" (AGC). METHODS: Cytologic follow-up was performed on 214 cases with ASC-H/AGC diagnosis an conventional smears using either ThinPrep (n = 100) or conventional Papanicoloau (Pap) tests (n = 114). Results were then compared with further histologic and/or cytologic follow-up. RESULTS: Repetition on conventional smears enabled a definite diagnosis (within normal limits [WNL], squamous intraepithelial lesion [SIL] or carcinoma) in 58 cases (50.9%). ASC/AGC was confirmed in 50 cases (43.9%), and 6 of the smears (5.3%) were inadequate. WNL, SIL, or carcinoma was diagnosed in 82 (82.0%) cases by following the patients with ThinPrep cytology, whereas ASC or AGC was confirmed in 18 cases (18.0%). No inadequate specimens were found. A diagnosis of SIL or greater (SIL +) was confirmed histologically in 11 of 11 (100.0%) conventional smears and in 31 of 34 (91.2%) ThinPrep specimens. Of the 87 WNL specimens, 9 (8 conventional smears and 1 ThinPrep specimen) developed a histologically confirmed SIL during further follow-up. Specimen adequacy was significantly better in the ThinPrep specimens compared with conventional smears. CONCLUSIONS: Because of better specimen adequacy, ThinPrep cervical cytology appears to significantly reduce the occurrence of ASC/AGC compared with conventional Pap smears.     

Cytohistologic correlation rates between conventional Papanicolaou smears and ThinPrep cervical cytology: a comparison

BACKGROUND: The ThinPrep Papanicolaou (Pap) test, a liquid-based alternative to the long-used conventional Pap smear, received Food and Drug Administration approval in 1996. The current study is a comparison of the accuracy, as assessed by cytohistologic correlation, of conventional versus ThinPrep Pap smears in a hospital setting. METHODS: A retrospective analysis of all patients who underwent Pap smears (conventional and ThinPrep) and pertinent surgical pathology tissue processed in our department over a 1-year period was undertaken. Tissue diagnoses were grouped into broad general categories to correlate with the Bethesda system. The statistical significance of differences between the two types of Pap test results compared with tissue diagnoses was assessed using a chi-square test with 1 degree of freedom and an alpha value of 0.05. RESULTS: Of the 65,421 Pap smears interpreted during the study period, histologic correlation was possible in 1544 patients. Of those diagnosed as negative (644 conventional and 245 ThinPrep Smears), low-grade squamous intraepithelial lesion (LGSIL) (116 conventional and 114 ThinPrep smears), and high-grade squamous intraepithelial lesions (HGSIL) (142 conventional and 131 ThinPrep smears), there was no statistically significant difference found between the correlation rates of conventional and ThinPrep Pap smear results. However, review of all cases of invasive cervical carcinoma identified during this time period showed the ThinPrep to be less consistent in predicting the presence of invasive carcinoma compared with the conventional Pap smear. CONCLUSIONS: Based on cytohistologic correlation evidence, the ThinPrep Pap test may not be more effective in detecting cervical disease, particularly invasive carcinoma, when compared with the conventional Pap smear.     

Significance of a diagnosis of atypical squamous cells of undetermined significance for Papanicolaou smears in perimenopausal and postmenopausal women

BACKGROUND: The current study was conducted to determine the significance of a diagnosis of atypical squamous cells of undetermined significance (ASCUS) in perimenopausal and postmenopausal women. METHODS: The reports for all Papanicolaou (Pap) smears viewed in the study institution's cytology laboratory over a 6-month period were reviewed. Women were divided into premenopausal (age < or = 45 years), perimenopausal (ages 46-54 years), and postmenopausal (age > or = 55 years) categories. Slide review and 2-year follow-up were obtained for selected cases diagnosed as ASCUS. ASCUS cases among the perimenopausal women were compared with an age-matched control group. RESULTS: The total number of abnormal Pap smears in the premenopausal, perimenopausal, and postmenopausal categories were 770 (6.8%), 104 (4.3%), and 67 (2.9%), with 482, 83, and 41 diagnoses of ASCUS, respectively. The ratio of ASCUS to squamous intraepithelial lesions (SIL) was 2.2 overall and 1.9, 7.5, and 4.1, respectively, for each group (P < 0.001). The positive predictive value for a diagnosis of SIL on subsequent Pap smears or biopsies was 22%, 12.2%, and 29.7%, respectively. Slide review showed that the premenopausal ASCUS cases appeared to have a higher percentage of nuclear-cytoplasmic ratio increase and nuclear membrane irregularities compared with the other categories (P = 0.03 and P = 0.02, respectively) and the perimenopausal group was found to have more ASCUS in metaplastic cells (P = 0.03). In perimenopausal women, slides diagnosed as ASCUS demonstrated more air-drying artifact than the control group (P = 0.004) but had less obvious atrophy (P = 0.01). CONCLUSIONS: Despite a decreased abnormality rate with increasing age, the results of the current study show that the perimenopausal and postmenopausal groups appear to have elevated ASCUS-to-SIL ratios. ASCUS appears to have a particularly low positive predictive value for SIL in perimenopausal women, and therefore most likely is overcalled in this age group. This may be attributable in part to air-drying artifact and subtle atrophic changes.     

ThinPrep Pap Test: performance and biopsy follow-up in a university hospital.

BACKGROUND: The ThinPrep Pap Test (TP), a liquid-based cervical cytology preparation, was approved for use in the U.S. in 1996. The purpose of this study was to compare TP performance and biopsy follow-up studies with a similar population of high risk patients sampled by conventional Papanicolaou (Pap) smear (CS). METHODS: Diagnostic and specimen adequacy interpretations for 2727 TP direct-to-vial Pap tests from a high risk university hospital practice were compared with 5000 CS preparations from the same physicians taken 1 year previously. Biopsy follow-up studies for the categories of squamous intraepithelial lesion (SIL), carcinoma, and atypical squamous cells of undetermined significance (ASCUS) for each time period and technique were contrasted. RESULTS: The SIL/carcinoma detection rate increased from 7.7% to 10.5% (P < 0.01) and the ASCUS rate decreased from 12.5% to 6.9% (P < 0.01); the percentage of satisfactory but limited specimens decreased from 19.4% to 10.5% (P < 0.01). Low grade SIL cases increased by 57% (P < 0.01) whereas the 26% increase in high grade SIL cases was not statistically significant. Greater than 90% of ungraded SIL, high grade SIL, and carcinoma cases had abnormal biopsies by both the TP and CS methods. The number of biopsy-confirmed high grade dysplasias and carcinomas was similar in the two groups. A low grade SIL detected by TP was less likely to have an abnormal biopsy (70% vs. 85% for CS). Nevertheless, the 57% increase in low grade SIL diagnoses by TP resulted in more TP patients with dysplastic biopsy diagnoses. Follow-up studies for ASCUS cases diagnosed by either TP or CS were similar, and 21-24% of patients eventually were found to have dysplasia. CONCLUSIONS: The TP technique appears to lead to the increased detection of low grade SIL lesions, decreased satisfactory but limited samples, and fewer equivocal specimens. No increase in biopsy-confirmed high grade dysplasias and carcinomas was found. Follow-up studies for the ASCUS category were nearly identical to those for CS.     

ThinPrep detection of cervical and endometrial adenocarcinoma: a retrospective cohort study

BACKGROUND: The current study was performed to compare the accuracy of the ThinPrep trade mark Papanicoloau (Pap) test with that of the conventionally prepared Pap smear in detecting cervical and endometrial adenocarcinomas. METHODS: The subject group consisted of all ThinPrep cases of atypical glandular cells of undetermined significance (AGCUS) or adenocarcinoma diagnosed between March 1998 and March 2000. Conventional smears collected between January 1996 and January 1998, before laboratory conversion to the ThinPrep system, comprised the control group. Histologic follow-up was obtained. RESULTS: One hundred eighty-six (0.17%) of 112,058 ThinPrep Pap tests were interpreted as AGCUS/adenocarcinomas, compared with 77 (0.09%) of 83,464 conventional smears (P < 0.001). The overall sensitivity of a ThinPrep AGCUS/adenocarcinoma smear in detecting either cervical or endometrial adenocarcinoma was increased (72.0% vs. 41.5%; P < 0.001). The ThinPrep Pap test was more sensitive in detecting endometrial adenocarcinomas (65.2% vs. 38.6%; P = 0.010) and there was a trend for a higher sensitivity in detecting cervical adenocarcinomas (87.1% vs. 55.5%; P = 0.108). CONCLUSION: The ThinPrep Pap test is a more sensitive method of detecting cervical and endometrial adenocarcinomas than the conventional Pap smear.     

Increased incidence of atypical Papanicolaou tests from ThinPreps of postmenopausal women receiving hormone replacement therapy.

BACKGROUND: The authors noticed a significant increase in the rate of atypical squamous cells of undetermined significance (ASCUS) diagnoses in postmenopausal women receiving hormone replacement therapy with ThinPrep (monolayer) Papanicolaou (Pap) tests (8.3%) as compared with conventional Pap tests (2.3%; P = 0.025). The purpose of this study was to correlate these morphologic changes with human papillomavirus (HPV) DNA detection by in situ hybridization and clinical outcome. METHODS: Twenty-five monolayer Pap tests diagnosed as ASCUS in postmenopausal women receiving hormone replacement, as well as 2 cases of low-grade squamous intraepithelial lesion (SIL) from the same group, were destained in acid alcohol. In situ HPV hybridization was performed with a consensus probe that can detect greater than 90% of the HPV types that occur in cervical SIL. In addition, 11 of the ASCUS tests were analyzed with the periodic acid-Schiff (PAS) stain. RESULTS: All 25 ASCUS tests were negative for HPV DNA as compared with a detection rate of 15 of 17(88%) for low-grade SIL. Glycogen that was PAS positive was present in the atypical squamous cells of the postmenopausal women for whom HPV was not detected. Clinical follow-up demonstrated that only 2 of the 25 women with ASCUS had a subsequent biopsy proven SIL. CONCLUSIONS: The ThinPrep preparation can produce artifactual HPV-like changes in postmenopausal women receiving hormone replacement therapy that may be caused by glycogenization and, because of the high incidence of HPV negativity and negative clinical outcome, are best considered as benign cellular changes.     

Real-time,high-definition,three-dimensional microscopy for evaluating problematic cervical Papanicolaou smears classified as atypical squamous cells of undetermined significance

BACKGROUND: The perceived inadequacies of the cervical Papanicolaou (Pap) smear have been attributed to sampling, screening, or interpretive errors. Within this type of cytologic preparation, there are thick cell clusters in which the cells are obscured. It may not possible to evaluate these areas by conventional microscopy. The authors clinically tested the hypothesis that high-definition, three-dimensional (3-D) microscopy based on multiple oblique illumination (MOI), with its ability to penetrate into thick areas, would be useful in evaluating problematic cervical Pap smears, particularly those diagnosed as atypical squamous cells of undetermined significance (ASCUS).METHODS:ASCUS Pap smears and corresponding surgical biopsy specimens were evaluated prospectively using standard, axially illuminated microscopes and a new high-definition, 3-D microscope employing MOI. The Pap smears were reviewed in a blinded fashion with both types of microscopy. The rendered diagnoses were then compared with the subsequent tissue biopsies, which also were blinded, as the definitive end point.RESULTS: It was immediately apparent that the high-definition, 3-D MOI microscope had better resolution compared with the standard microscopes. Pap smears and biopsy diagnoses were correlated significantly for MOI (P < 0.001), and there were significant improvements (P = 0.0108) in accuracy when 3-D, high-definition microscopy was compared with conventional microscopy. The authors found no statistically significant correlation between ASCUS diagnoses that were rendered by using standard microscopes compared with the subsequent biopsy.CONCLUSIONS: Due to enhanced visualization through thick cell clusters, an increased depth of field, light penetration, and resolution, high-definition, 3-D microscopy based on MOI produced superior accuracy compared with conventional light microscopy in evaluating cervical Pap smears.     

Atypical squamous cells of undetermined significance in liquid-based cytologic specimens: results of reflex human papillomavirus testing and histologic follow-up in routine practice with comparison of interpretive and probabilistic reporting methods

BACKGROUND: Human papillomavirus (HPV) DNA testing for high-risk types after Papanicolaou (Pap) smear interpretations of atypical squamous cells of undetermined significance (ASCUS) is a sensitive method for identifying women who harbor underlying high-grade squamous intraepithelial lesions (HSIL). To the authors' knowledge, the application of HPV testing to ASCUS smears in routine practice with comparison of probabilistic and interpretive models of cytologic reporting has not been reported. METHODS: HPV DNA testing was performed reflexively on 216 liquid-based Pap smears that initially were interpreted as ASCUS. According to the interpretive model, ASCUS interpretations were modified and reported as either low-grade squamous intraepithelial lesions (LSIL) or squamous intraepithelial lesions (SIL) when HPV positive and as reactive when HPV negative. Using the probabilistic model, ASCUS interpretations were maintained and simply reported with the HPV test result. Histologic follow-up data were obtained. RESULTS: Of the 216 women with ASCUS cytology, 142 (65.7%) were positive for high-risk HPV types. Of the 142 HPV-positive ASCUS smears, 101 (71.1%) were modified to an interpretation of LSIL (96 cases) or SIL (5 cases). Histologic follow-up of 55 of the 101 HPV-positive smears in the interpretive group and 26 of the 41 HPV-positive smears in the probabilistic group yielded similar percentages of lesions (18 lesions [32.7%] and 9 lesions [34.6%], respectively). However, there was a preponderance of low-grade lesions in the interpretive group (89%) but a nearly equal distribution of low-grade and high-grade lesions in the probabilistic group (56% and 44%, respectively); overall, 22% of the lesions were high-grade. Of the 74 HPV-negative ASCUS smears, 71 (96%) were modified to reactive and all 5 with histologic follow-up were judged as negative. CONCLUSIONS: Colposcopy with tissue studies was virtually restricted to HPV-positive cases, regardless of the reporting model used, suggesting that clinicians are basing colposcopy triage on the HPV test result rather than the definitiveness of the cytologic interpretation. This observation, the similar yield of lesions in both groups, and the significant risk of high-grade lesions argue against application of the interpretive model to HPV-tested ASCUS cases.     

Value of colposcopy in the early diagnosis of cervical cancer in patients with abnormal pap smears at Shahid Sadoughi hospital, Yazd

Background and objectives: Cervical cancer is preventable, although it is common in developing countries and Iran, where there is no defined approach to “atypical squamous cells of undetermined significance” (ASCUS) on Pap smears. This study determined the value of colposcopy in the early diagnosis of cervix cancer in females with ASCUS. Materials and methods: This accuracy study examined 213 ASCUS cases referred from different cities from 2007 to 2009. All patients underwent a repeated conventional Pap smear, colposcopy, endocervical curettage, and a cervical biopsy, considered the gold-standard diagnostic test. Results: There was no significant relationship between age, age of first intercourse, smoking, or number of children and a positive cervical biopsy. The sensitivity and specificity of a repeat Pap smear for ASCUS were 15 and 93%, respectively, while the respective values for diagnosing cervical cancer with colposcopy were 80 and 80%. Endocervical curettage had 64% sensitivity and 100% specificity for diagnosing cervical cancer, and 11 positive neoplastic or malignant lesions reported on endocervical curettage were confirmed by biopsy. Discussion: Based on the low accuracy of the Pap smear in Iran as a developing country and the need for an early diagnosis of cervical cancer, a cervical biopsy and colposcopy are recommended for these patients. Colposcopy and endocervical curettage alone are better diagnostic tools than a repeat Pap smear for unsatisfactory Pap smears.     

Chemopreventive potential and safety profile of a Curcuma longa extract in women with cervical low-grade squamous intraepithelial neoplasia

Objective: To determine whether Curcuma longa Linn extract, NBFR-03, can arrest low-grade squamous intraepithelial neoplasia (LSIL) a 12 week intervention study was performed. Methods: Of a total of 1473 women undergoing Pap smear screening, 88 cases had LSIL. Only those with persistent LSIL subsequent to antimicrobial therapy, and willing to follow the protocol (N=21), were included for clinical examination, Pap smears, colposcopy, clinical biochemistry, urinalysis and assessment of serum IL-6, being condcuted before and after treatment. Standardised NBFR-03 (0.2gm) capsules were administered, twice daily, for 12 weeks. Results: None progressed to higher grade lesion as assessed by Pap smears and colposcopy. Sixteen cases regressed to atypia, ASCUS or inflammatory pattern; 3 persisted as LSIL, 1 discontinued early because of itching, and 1 did not start. None developed any significant abnormality clinically or biochemically. Micrometry showed a significant reduction in nuclear diameter and nucleocytoplasmic ratio after treatment (p<0.02, and <0.05 respectively). Serum IL-6 levels showed a significant decline (mean 248± 156 (SEM) vs 27.7± 10.5 (SEM) pg/ ml; p<0.05). Conclusion: Use of NBFR-03 for 12 weeks was associated with an arrest or regression of LSIL in Pap smears and colposcopy, with reduction in the circulating IL-6 levels.     

Association of Abnormal Pap Smear with Occult Cervical Stromal Invasion in Patients with Endometrial Cancer

Objective: The purpose of this study was to determine the association between abnormal preoperative Pap smearresults and occult cervical stromal invasion in endometrial cancer patients. Methods: Medical records were reviewed ofpatients with endometrial cancer who had undergone surgical staging at Srinagarind Hospital. Patients with gross cervicalinvolvement, with an unsatisfactory Pap smear, without available Pap smear results, with no cervical intraepitheliallesion/invasive cervical cancer, or who had previously undergone pelvic radiation therapy were excluded. The patientswere assigned to one of two groups according their Pap smear results (negative and epithelial cell abnormalities).Logistic regression was used to determine the independent association between an abnormal Pap smear and the riskof cervical stromal invasion. Results: All cervical smears in this study were performed as conventional Pap smears.Smears were abnormal in 50 (21.0%) of the 238 patients enrolled and normal in the remaining 188 (79.0%). The typesof Pap smear abnormalities included adenocarcinoma (n=22); atypical endometrial cells (n=2); atypical glandular cells(n=17); high-grade squamous intraepithelial lesions (n=4); atypical squamous cells, cannot exclude high-grade squamousintraepithelial lesions (n=2); and atypical squamous cells of undetermined significance (n=3). After controlling for type ofendometrial cancer, abnormal Pap smear results were found to be a significant independent factor that indicated cervicalstromal invasion (adjusted OR 2.65; 95% CI 1.35 to 5.21). Conclusion: Endometrial cancer patients with abnormalPap smears were strongly and independently associated with histopathologically diagnosed cervical stromal invasion.     

Expression of P-glycoprotein is Positively Correlated with p53 in Human Papilloma Virus Induced Squamous Intraepithelial Lesions of Uterine Cervix: Poor Prognosis Association

This study was conducted to assess the predictive value of p-glycoprotein (p-gp) and p53 immunoexpression in human papillomavirus (HPV) infected cases of cervical dysplasia. Expression of both p-gp and p53 proteins was detected in cervical smears from 177 squamous intraepithelial lesions (SIL) cases along with 183 “atypical squamous cells of unknown significance” (ASCUS) and 150 normal cases. HPV 16 and 18 infection was detected by polymerase chain reaction using type-specific primers for HPV sub-types. There were no significant detectablep53 and p-gp expression in the normal cervix smears (p>0.05). In the ASCUS group 10 cases were positive for both p53 and p-gp immunoreactivity. In cervical dysplasia cases, p53 was positive in 86 (48.58%) while p-gp waspositive in 93 (52.54%) and the two markers showed a highly significant correlation (r=0.92, p<0.001). Expression of p53 and p-gp was associated with grade of SIL (p<0.001). A positive correlation between the presence of HPVand expression of proteins p53 and p-gp in smears of patients with cervical lesions was also noted (p<0.001).Thus, p53 and p-gp immunostaining in cervical smears may act as an auxiliary biomarker for detection of HPV-associated cervical lesions. Additionally, a significant positive correlation between ascending grades of SIL and labeling indices of markers suggests that p53 and p-gp can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smears.     

Liquid-based cytology and conventional cervical smears: a comparison study in an Asian screening population

BACKGROUND: This study compared the findings of cervical cytology screening by ThinPrep Papanicolaou (Pap) tests (TP) with the findings of screening by conventional cervical smears (CS) in a screening population involving what to the authors' knowledge is the largest sample of ThinPrep Pap tests published to date. METHOD: Data from 191,581 CS that were screened in the period from March 1, 1998 to February 28, 2000 were compared with data from 190,667 TP performed from March 1, 2000 to February 28, 2002 and that were obtained from the same sources. RESULTS: With TP, the unsatisfactory rate was reduced from 0.48% to 0.32%. Fewer cases were considered to be suboptimal (19.12% vs. 12.97%). The detection rates of squamous cell carcinomas, adenocarcinomas, and high-grade squamous intraepithelial lesions (HSIL) were essentially unchanged in the TP group (0.005%, 0.003%, and 0.25%, respectively) compared with the rates for the CS group (0.01%, 0.006%, and 0.25%, respectively). There was an increase in the detection of atypical squamous cells of undetermined significance (ASCUS; 3.74% vs. 3.19%) and low-grade SIL (LSIL; 1.67% vs. 1.01%) with a decrease in the ASCUS-to-LSIL ratio from 3.15 for CS to 2.33 for TP. The detection of atypical glandular cells of undetermined significance (AGUS) increased slightly from 0.07% to 0.09%. The proportion of cells reported to have reactive atypia dropped from 2.71% to 1.48%. Limited biopsy correlation (range, 73.2-76.2%) confirmed the increased sensitivity of TP. More actinomyces (1.07% vs. 0.52%) were detected in TP samples despite of a similar portion of intrauterine-device users. The average primary screening and rapid rescreening time of each slide were reduced from 8 minutes to 4 minutes and from 2 minutes to less than 1 minute, respectively. CONCLUSIONS: The preliminary experience of the authors of the current study appears to support the use of the ThinPrep Pap test to enhance the efficiency of cervical cytology screening.     

Prevalence and Risk Factors of Cervical Dysplasia among Human Immunodeficiency Virus Sero-Positive Females on Highly Active Antiretroviral Therapy in Enugu,Southeastern, Nigeria

Objective: Evaluation of prevalence and risk factors of cervical dysplasia among Human Immunodeficiency Virus sero-positive (HIV+ve) females on Highly Active Antiretroviral Therapy (HAART) attending HIV clinic at University of Nigeria Teaching Hospital (UNTH) Enugu, Southeastern, Nigeria. Methods: Structured questionnaire was used to obtain socio-demographic and risk factors data. Cervical specimens were collected from 105 HIV +ve females on HAART and 104 HIV seronegative (HIV–ve) females. Pap smears were collected using cytobrush and Ayre’s spatula in a secluded place. Smears were made on slides and placed in 95% ethyl alcohol for conventional Pap staining and the cytobrush washed into the preservative containers for later Immunocytochemistry staining. Blood samples were used for HIV screening. Immunocytochemistry activity using anti-P16INK4A was carried out on the Pap smears that were positive for cervical dysplasia. Results: Pap staining showed prevalence of cervical dysplasia among HIV+ve on HAART 19.05%, (ASCUS 14.29%, LSIL 3.81%, HSIL 0.95%) whereas HIV-ve was 6.73%, p = 0.008. Only the HSIL 0.95% was positive for P16INK4A. Odds ratios at 95% Confident Interval of the risk factors of cervical dysplasia were thus; HIV+ve, 3.26 (1.31-8.09), education less than secondary school 3.23 (1.25-8.37), polygamy 3.23 (1.25-8.37), smoking 1.36 (0.15-12.10), married 2.08 (0.43-2.31), grand multi gravidity 1.72 (0.72-4.11), grand multi parity 1.54 (0.66-3.61), positive history of sexually transmitted diseases 2.49 (1.06-5.80). Uptake of cervical cancer screening was low in both study groups, 7 (6.7%) among HIV+ve on HAART and 14 (13.5%) among HIV-ve females, P = 0.102. Conclusion: HAART had cytoprotective effect against cervical dysplasia in HIV+ve females, by reducing progression of ASCUS to LSIL, HSIL and cervical cancer. Progression from normal to ASCUS increased which could be due to latency or/and prolonged persistent high risk HPV and HIV infections, of the most sexually active age group before diagnosed of HIV.     

A comparison of liquid-based cytology and Pap smear as a screening method for cervical cancer

The implementation of population-based screening for cervical cancer with Pap smear in the early sixties was set to detect and treat precancerous lesions, hopefully preventing a subsequent invasive cervical cancer. Epidemiological data indicate that organized screening has a major impact on morbidity and mortality from cervical cancer. The limited sensitivity of a single smear necessitates repeated smears in organized program. It is suggested that liquid-based cytology improves the sensitivity. The aim of this split-sample study was to compare ThinPrep liquid-based cytology with conventional Pap smear, relying on a laboratory with long-term experience of the latter. In total, 137 women with atypical Pap smear in population-based cervical screening were enrolled for the split-sample study. The performance of both techniques (ThinPrep liquid-based cytology and conventional Pap smear) were compared and validated by a histological follow-up. Women without representative histological biopsy were excluded from the study. Pap smear had sensitivity for detection of CIN2-3 of 47% compared to 66% for liquid-based material. The concordance of the two sampling techniques with the histological diagnosis was 37% and 53%, respectively, this difference being statistically significant. The proportion of reports on atypical squamous cells of undetermined significance (ASCUS) was significantly less in the liquid-based material, 4.3% compared to 8% of the conventional smears. This improved sensitivity in combination with the possibility to perform reflex testing such as HPV DNA or p16 immunocytochemistry without renewed sampling gives ThinPrep a substantial advantage and makes the liquid-based technique interesting.