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.     

Liquid-based cytology for primary cervical cancer screening: a multi-centre study

The aim of this six-centre, split-sample study was to compare ThinPrep fluid-based cytology to the conventional Papanicolaou smear. Six cytopathology laboratories and 35 gynaecologists participated. 5428 patients met the inclusion criteria (age > 18 years old, intact cervix, informed consent). Each cervical sample was used first to prepare a conventional Pap smear, then the sampling device was rinsed into a PreservCyt vial, and a ThinPrep slide was made. Screening of slide pairs was blinded (n = 5428). All non-negative concordant cases (n = 101), all non-concordant cases (n = 206), and a 5% random sample of concordant negative cases (n = 272) underwent review by one independent pathologist then by the panel of 6 investigators. Initial (blinded) screening results for ThinPrep and conventional smears were correlated. Initial diagnoses were correlated with consensus cytological diagnoses. Differences in disease detection were evaluated using McNemar's test. On initial screening, 29% more ASCUS cases and 39% more low-grade squamous intraepithelial lesions (LSIL) and more severe lesions (LSIL+) were detected on the ThinPrep slides than on the conventional smears (P = 0.001), including 50% more LSIL and 18% more high-grade SIL (HSIL). The ASCUS:SIL ratio was lower for the ThinPrep method (115:132 = 0.87:1) than for the conventional smear method (89:94 = 0.95:1). The same trend was observed for the ASCUS/AGUS:LSIL ratio. Independent and consensus review confirmed 145 LSIL+ diagnoses; of these, 18% more had been detected initially on the ThinPrep slides than on the conventional smears (P = 0.041). The ThinPrep Pap Test is more accurate than the conventional Pap test and has the potential to optimize the effectiveness of primary cervical cancer screening.     

Results of the implementation of liquid-based cytology-SurePath in the Ontario screening program

BACKGROUND: The objective of the current study was to evaluate the adequacy and detection rates of SurePath after its implementation in Ontario. METHODS: The detection and adequacy rates of the SurePath liquid-based cytology system (SP-LBC) were calculated for manually reviewed slides of the year 2002. The adequacy and detection rates from this study group were compared with a historical conventional smear (CS) group from the same laboratories during the same period of the previous year. RESULTS: The SP-LBC study group consisted of 352,680 specimens with cytodiagnoses and the CS group included 378,990 specimens. The unsatisfactory rate for SP-LBC (0.24%) was less than that of the CS group (0.58%). The detection rate of atypical squamous cells (ASC+) by the SP-LBC group (4.69%) was greater than that of the CS group (3.81%), as was the detection rate of low-grade squamous intraepithelial lesions (LSIL+; 2.13% vs. 1.50% in the CS group). There was only a trend toward increased detection of high-grade squamous intraepithelial lesions (HSIL+) in the SP-LBC group (0.34%) relative to the CS group (0.31%), because the detection rate for carcinoma by SP-LBC declined. CONCLUSIONS: The implementation of SP-LBC has been followed by better specimen adequacy and detection rates for ASC+, LSIL+, and a trend of increased detection of HSIL+ relative to CS practice. To determine sensitivity rates, a histopathologic database for cervical carcinoma and precancer needs to be established.     

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 significance of the Papanicolaou smear diagnosis of low-grade squamous intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion

BACKGROUND: Cervical cytologic specimens that show a low-grade squamous intraepithelial lesion (LSIL) occasionally contain a few cells that are suspicious for, but not diagnostic of, a high-grade squamous intraepithelial lesion (HSIL). In such cases, a diagnosis of LSIL cannot exclude HSIL is rendered. The objective of the current study was to assess the positive predictive value (PPV) for HSIL in follow-up cervical biopsies for these cases. METHODS: One hundred forty-four women with a Papanicolaou (Pap) diagnosis of LSIL cannot exclude HSIL and their follow-up cervical biopsies were reviewed. Results were compared with a control group of 155 women with a Pap diagnosis of LSIL. A subset of biopsies was tested and typed for human papillomavirus (HPV) DNA by polymerase chain reaction amplification using consensus primers followed by restriction fragment length polymorphism analysis. HPVs were scored as low-risk or high-risk types. RESULTS: Women with LSIL cannot exclude HSIL had a higher incidence of HSIL (PPV = 29%) on follow-up cervical biopsy than the control group (PPV = 15%, P < 0.01). In addition, SIL, indeterminate grade was diagnosed in 10% of cervical biopsies in the study group as compared with 4% in controls. Review of Pap smears from the study group showed that there were 3 types of cells suspicious for a high-grade lesion: atypical squamous metaplastic cells (62%), atypical keratinized cells (20%), and dysplastic cells of borderline nuclear-to-cytoplasm ratio (18%). HPV analysis confirmed the presence of high-risk HPV types in the study cases with high-grade cervical biopsies. CONCLUSIONS: Women with a Pap diagnosis of LSIL cannot exclude HSIL appear to be more likely to harbor a high-grade lesion than those diagnosed with LSIL alone. Its use appears warranted. Women with this diagnosis merit appropriate clinical follow-up to exclude HSIL.     

液基细胞学筛查宫颈癌的研究

目的 评价ThinPrep液基细胞学在宫颈癌高发区筛查的准确性。方法 1997年例受检者同时做宫颈脱落细胞液基标本采集和阴道镜活检,用液基标本做薄片细胞学诊断和肿瘤相关人乳头瘤病毒（human papilloma virus,HPV)检测。细胞学诊断采用TBS分级系统,阳性诊断包括意义不明的不典型鳞状细胞（ASCUS）以上病变,诊断结果与阴道活检诊断和肿瘤相关HPV DNA阳性检出率对照。所有检查均双盲进行。结果 ThinPrep液基细胞学检出100％（12／12）的鳞状细胞癌（SCC）;93．2％（69／74）的鳞状上皮内高度病变（HSIL）,其中CIN396．8％（30／31）,CIN90．7％（39／43）;72．4％（92／127）的鳞状上皮内低度病变（LSIL）。SCC和CIN3的分级准确率分别达100％和87．1％。HPVDNA阳性检出率与细胞学分级密切相关,且在细胞学与组织学相同级别基本一致。结论 宫颈液基标本收集方法有利于细胞学和肿瘤相关HPV DNA双重检查。ThinPrep液基细胞学检查敏感性高,尤其是对鳞状上皮内高度病变。     

Does the interval between papanicolaou tests influence the quality of cytology?

BACKGROUND: It is commonly believed that the sensitivity of Papanicolaou (Pap) tests decreases with a short interval between cytology samplings. To the authors' knowledge, there is only limited evidence to support this belief. METHODS: For 5055 women in the Atypical Squamous Cells of Undetermined Significance (ASCUS)-Low Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS), the Pap interval was defined as the number of days between the referral Pap smear demonstrating ASCUS or LSIL ("first cytology") and the enrollment liquid-based ("repeat") cytology. The authors investigated the influence of the interval between Pap smears on repeat cytology by examining percentages of abnormal findings, cellularity, and test sensitivity among women diagnosed with histologic grade 3 cervical intraepithelial neoplasia (CIN3) during the 2-year course of the ALTS. In addition, because human papillomavirus (HPV) DNA adjunct testing is now performed, the authors evaluated HPV viral load, which was assayed using residual liquid cytology specimens, in women with CIN3. RESULTS: The Pap interval ranged from 8-30 days in 763 women, 31-60 days in 2317 women, 61-90 days in 1090 women, 91-120 days in 491 women, and 121-184 days in 394 women (mean of 61.3 days; standard deviation of 34 days). Repeat cytologic interpretations of unsatisfactory findings, ASCUS, and high-grade squamous intraepithelial lesion (HSIL) did not appear to vary among the Pap interval groups. However, low-grade cytologic regression occurred with an increasing Pap interval; negative cytology increased from 28.3% (8-30 days) to 41.6% (121-184 days) (P < 0.0001) whereas LSIL cytology decreased (P trend = 0.002). The approximate cellularity of the samples was slightly better in the interval group of 8-30 days (P trend = 0.04). Among women with CIN3, the repeat test sensitivity at a threshold of ASCUS or greater and the HPV DNA viral load was not found to vary by Pap interval (P trend = 0.80 and P trend = 0.36, respectively). CONCLUSIONS: The authors concluded that a short Pap interval (range, 15-120 days) does not significantly affect the quality of liquid-based repeat cytology, nor the viral load tested from a residual liquid-based specimen.     

Performance of Siriraj Liquid-Based Cytology: a Single Center Report Concerning over 100,000 Samples

Background: To evaluate the performance of Siriraj liquid-based cytology (LBC) for cervical neoplasiascreening after increasing use of this technology. Materials and Methods: Cytological reports of 103,057Siriraj-LBC specimens obtained in 2007-2009 were compared with those of 23,676 specimens obtained in 2006.Results: Comparing with the year 2006, the 2007-2009 patients were slightly older (43.4±12.yr vs 42.7±12.2yr, p <0.001), and their specimens had much lower proportion of unsatisfactory slides (OR=0.06, 95%CI0.04-0.09) with comparable detection rates (3.96% vs 3.70%, p=0.052) but different proportions of variouscytological abnormalities (p<0.001). The 2007-2009 Siriraj-LBC had a negative predictive value (NPV) forcervical intraepithelial neoplasia 2+ (CIN2+) of 97.6% and an overall positive predictive value (PPV) of 43.9%.The PPV for CIN2+ varied with types of abnormal cytology, from 13.7% to 93.8% in atypical squamous cellsof undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), atypical squamouscells cannot exclude HSIL (ASC-H), high-grade squamous intraepithelial lesion (HSIL), atypical glandularcells (AGC), to squamous cell carcinoma (SCC), respectively. The PPVs for CIN2+ in ASCUS and LSIL werecomparable, but the PPV for CIN1 was higher for LSIL than for ASCUS (41.63% vs 16.32%). Conclusions:Siriraj-LBC has demonstrated a stable detection rate and NPV for CIN2+ of >95% since the first year of use.The comparable PPVs for CIN2+ of ASCUS and LSIL suggests that these two conditions may undergo similarmanagement; other cytological abnormalities need immediate evaluation.     

Distribution and prevalence of human papillomavirus genotypes in routine pap smear of 2,470 korean women determined by DNA chip.

PURPOSE: We examined human papillomavirus (HPV) genotype distribution and prevalence from routine Pap smear cases in Korean women using DNA Chip.Patients and METHODS: A total of 2,470 cervical specimens from women attending routine Pap smear cytology screening in local hospitals was subjected to HPV test. HPV detection and genotyping were done using DNA Chip.RESULTS: HPV DNA was detected in 44.8% of the patients and in 58.7% of the 861 atypical lesions based on the Bethesda system, including 52.6% of 627 atypical squamous cells of undetermined significance (ASCUS), 69.0% of 168 low-grade squamous intraepithelial lesions (LSIL), and 89.4% of 66 high-grade squamous intraepithelial lesions (HSIL) cases. The most frequently found genotypes in all HPV-positive cases were HPV-16, HPV-52, and HPV-58. HPV-16 was the most prevalent type in within normal limits, ASCUS, and HSIL categories, whereas HPV-51 was most frequently found in LSIL. Multiple infection was identified in about 20% of HPV-positive cases and most of them were that by two different types. HPV-16 was present in the majority of multiple infection cases. A significant decrease in the percentage of multiple infection was observed in HSIL cases compared with ASCUS and LSIL.CONCLUSIONS: The distribution of HPV genotypes in Korean women was revealed to have differences to that of other regions, showing higher frequencies of HPV-52, HPV-58, and HPV-51. HSIL cases were mostly infected by sole HPV-16 whereas LSIL that by various HPV types, suggesting a certain type may become dominant over others as the disease progresses.     

Comparative sensitivities of ThinPrep and Papanicolaou smear for adenocarcinoma in situ (AIS) and combined AIS/high-grade squamous intraepithelial lesion (HSIL): comparison with HSIL

BACKGROUND: Despite the historic belief that cytologic screening offers little protection against cervical adenocarcinoma (CAC), there is emerging evidence that, by detecting the precursor lesion, adenocarcinoma in situ (AIS), cervical screening may reduce the incidence of CAC as it has for cervical squamous carcinoma. Because liquid-based cytology is fast replacing the conventional Papanicolaou smear (PS), it is important to establish that it is at least as effective in detecting AIS. METHODS: The authors calculated the sensitivities of PS and ThinPrep (TP) for 100 women with histologic AIS (from 160 PS slides and 60 TP slides), for 94 women with AIS+high-grade squamous intraepithelial lesion (HSIL) (from 151 PS slides and 50 TP slides), and for 558 women with HSIL (from 788 PS slides and 383 TP slides). All smears were taken up to 36 months before the histologic diagnosis. RESULTS: In no category was there a significant difference between PS sensitivity and TP sensitivity. The HSIL category had a significantly higher overall sensitivity than the other categories. However, when sensitivity was defined as cytologic detection of high-grade disease, there was no difference between any of the categories. For the detection of a high-grade glandular lesion, the presence of a concurrent histologic HSIL was associated with reduced sensitivity for the detection of AIS. CONCLUSIONS: The current results indicated that it may prove possible for cervical screening, with either PS or TP, to reduce the incidence of CAC.     

Cervical Papanicolaou smear abnormalities in inner city Bronx adolescents: prevalence, progression, and immune modifiers.

BACKGROUND: The aim of this study was to quantify the prevalence of cervical smear abnormalities in sexually active adolescents and identify the effect of immune-modifying conditions. METHODS: Two hundred seventy-one females ages 13-22 years attending a clinic for sexually transmitted disease (STD) evaluation had cervical Papanicoloau (Pap) smears and completed sexual history questionnaires. Results of all follow-up Pap smears were obtained. Medical charts were available for 54 patients with cytologic follow-up and were reviewed for the presence of immune-modifying conditions. Follow-up smear results for patients with and without immune-modifying conditions were compared. Abnormality rates for all cervical smears seen in 1995 at Montefiore Medical Center were also obtained. RESULTS: The smear abnormality rate for adolescents was 20. 7% (abnormal squamous cells of undetermined significance [ASCUS], 12. 2%; low grade squamous intraepithelial lesion [LGSIL], 7.7%; high grade squamous intraepithelial lesion [HGSIL], 0.7%) compared with all adult females, for whom the rate was 13.2% (ASCUS, 9.9%; LGSIL, 2.5%; HGSIL, 0.6%; carcinoma 0.2%) (P < 0.0002). Of 20 initial ASCUS patients, 6 (30%) showed LGSIL or HGSIL on follow-up. Chart review allowed the clinical immune status of 54 patients to be determined. Of 14 patients with an immune-modifying condition (9 HIV positive patients, 3 receiving oral steroids, 1 liver transplant patient receiving steroids, and 1 with intestinal lymphangiectasia), 11 (78. 6%) developed or maintained an abnormality on cytologic follow-up. Of 40 patients with no identifiable immune-modifying condition, 11 (27.5%) developed or maintained an abnormality on cytologic follow-up (P < 0.00082). CONCLUSIONS: Sexually active adolescents are at higher risk of developing a significant cervical smear abnormality, especially LGSIL. Patients with an atypical Pap smear or immune-modifying condition require more attentive gynecologic monitoring. Cancer (Cancer Cytopathol) Copyright 1999 American Cancer Society.     

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.     

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears

BACKGROUND: Developed in 1989, the Bethesda System has largely replaced previous classifications of Papanicolaou (Pap) smears from the uterine cervix. The system is binary, dividing smears into two groups - low-grade, squamous, epithelial lesions (LSIL) or high-grade, squamous, epithelial lesions (HSIL). A third category, atypical squamous cells of undetermined significance (ASCUS), is used to classify minimal cellular changes that do not satisfy the criteria for the low- or high-grade categories. This study was designed to confirm the utility of this binary division and to compare the results with another classification system (the Munich II Nomenclature) that is not binary but contains three divisions or grades for dysplasia - low, intermediate, and high. METHODS: Pap smears were obtained from 593 women with a cytologic diagnosis of dysplasia based on the Munich System. Smears were then classified by the Bethesda System into LSIL or HSIL. Patients were followed for 2 years either with biopsy or repeat cytology. The initial smears were restained by the Feulgen method, and ploidy was evaluated by interactive DNA cytometry. RESULTS: Of 241 cases of LSIL, 39% were diploid, 57% polyploid, and 4% aneuploid. Of 352 cases classified HSIL, 4% were diploid, 17% polyploid, and 79% aneuploid. After 2 years of follow-up, 2 of 108 patients who were biopsied and who were originally classified as diploid progressed to cervical intraepithelial neoplasia/carcinoma in situ (CIN/CIS) whereas 109 of 217 patients who were aneuploid and biopsied were found to have CINIII/CIS. CONCLUSIONS: The two divisions of the Bethesda System, LSIL and HSIL, correlated with ploidy as evaluated by cytometry. Aneuploidy was found to be useful to separate cases of HSIL from those of LSIL as defined in the Bethesda System. Because of the binary division, use of a system with three divisions for dysplasia, such as the Munich II Nomenclature, creates a therapeutic dilemma because a single diagnostic category (usually the intermediate grade) may contain both self-limiting and progressive lesions. DNA cytometry of Pap smears was found to be useful as a routine procedure.     

Combined p16INK4a and human papillomavirus testing improves the prediction of cervical intraepithelial neoplasia (CIN II-III) in Thai patients with low-grade cytological abnormalities

Thailand is in the process of developing a national cervical screening program. This study examined p16INK4a staining and HPV prevalence in abnormal cervical samples with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL), to evaluate the efficacy of combined HPV and p16INK4a detection to predict CIN II-III. Totals of 125 ASCUS and 87 LSIL cases were re-evaluated by Pap test and cervical cells of ASCUS and LSIL cases were prepared on slides for p16INK4a detection by immunocytochemistry. HPV genotyping of DNA extracts was performed by GP5+/6+ PCR and reverse line blot hybridization. Histopathologic tests were performed to identify cervical lesion. Total of 212 cases were diagnosed to normal (20), ASCUS (112), LSIL (78) and HSIL (2). HPV was detected in ASCUS (49/112, 43.8%), LSIL (60/78, 76.9%) and HSIL (2/2, 100%) cases. The majority of HPV positive samples typed for high-risk HPV. 55.7% (107/192) of abnormal cases (ASCUS, LSIL and HSIL) were positive p16INK4a. For the 111 HPV DNA positive cases, 34 of 49 (69.4%) ASCUS cases and 49 of 60 (81.7%) LSIL cases were p16INK4a positive. 140 biopsies were taken and histological classified: CIN negative (65 cases), CIN I (56 cases) and CIN II-III (19 cases). HPV DNA detection predicted CIN II-III with sensitivity and specificity of 84% and 49%, whereas p16INK4a staining showed higher sensitivity (89.5%) and specificity (56.2%). The prediction of CIN II-III was significantly better by combination of positive HPV DNA and p16INK4a with 93.8% sensitivity and 59.2% specificity. Detection of HPV DNA combined with p16INK4a in cervical cells can predict CIN II-III and may improve the screening diagnosis of Thai women at risk for CIN II-III or cancer.     

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.     

Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV-proofer and consensus PCR: A 2-year follow-up of women with ASCUS or LSIL Pap smear

It has been suggested that human papillomavirus (HPV) testing improves follow-up of atypical cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) in cervical cancer screening programs. To evaluate the prognostic value of including HPV testing as an adjunct to cytology, we carried out a 2-year follow-up study of 77 women with ASCUS or LSIL Papanicolaou (Pap) smear in the Norwegian Cervical Cancer Screening Program (NCCSP) for detection of histological cervical intraepithelial neoplasia (CIN) 2+. The study includes a comparison between viral mRNA and DNA detection. PreTect HPV-Proofer was used for HPV E6/E7 mRNA detection from the 5 high-risk types 16, 18, 31, 33 and 45, and Gp5+/6+ consensus PCR was used for HPV DNA detection. Twice as many women were positive for HPV DNA (54.6%) than for HPV mRNA (23.4%). PreTect HPV-Proofer and consensus PCR had a sensitivity of 85.7% (95% confidence interval [CI] = 42.1-99.6) for detecting CIN2+ during follow-up. The specificity was significantly higher for PreTect HPV-Proofer, 84.9% (95% CI = 73.9-92.5), than for consensus PCR, 50.0% (95% CI = 37.4-62.6). PreTect HPV-Proofer positive women were 69.8 times (95% CI = 4.3-1137.3) more likely to be diagnosed with CIN2+ within 2 years than PreTect HPV-Proofer negative women. Consensus PCR-positive women were 5.7 times (95% CI = 0.6-52.0) more likely to be diagnosed with CIN2+ within 2 years than PCR-negative women. With equal sensitivity and higher specificity than consensus PCR, the PreTect HPV-Proofer might offer an improvement for the triage of women with ASCUS or LSIL Pap smear.     

Comparative sensitivities of ThinPrep and Papanicolaou smear for adenocarcinoma in situ (AIS) and combined AIS/high‐grade squamous intraepithelial lesion (HSIL): Comparison with HSIL

BACKGROUND.

Despite the historic belief that cytologic screening offers little protection against cervical adenocarcinoma (CAC), there is emerging evidence that, by detecting the precursor lesion, adenocarcinoma in situ (AIS), cervical screening may reduce the incidence of CAC as it has for cervical squamous carcinoma. Because liquid‐based cytology is fast replacing the conventional Papanicolaou smear (PS), it is important to establish that it is at least as effective in detecting AIS.

METHODS.

The authors calculated the sensitivities of PS and ThinPrep (TP) for 100 women with histologic AIS (from 160 PS slides and 60 TP slides), for 94 women with AIS+high‐grade squamous intraepithelial lesion (HSIL) (from 151 PS slides and 50 TP slides), and for 558 women with HSIL (from 788 PS slides and 383 TP slides). All smears were taken up to 36 months before the histologic diagnosis.

RESULTS.

In no category was there a significant difference between PS sensitivity and TP sensitivity. The HSIL category had a significantly higher overall sensitivity than the other categories. However, when sensitivity was defined as cytologic detection of high‐grade disease, there was no difference between any of the categories. For the detection of a high‐grade glandular lesion, the presence of a concurrent histologic HSIL was associated with reduced sensitivity for the detection of AIS.

CONCLUSIONS.

The current results indicated that it may prove possible for cervical screening, with either PS or TP, to reduce the incidence of CAC. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

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.