High-grade Lesions (high-grade + lesion)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Molecular cytogenetic characterization of early and late renal cell carcinomas in Von Hippel-Lindau disease ,

GENES, CHROMOSOMES AND CANCER, Issue 1 2001
John L. Phillips
Deletions of 3p25, gains of chromosomes 7 and 10, and isochromosome 17q are known cytogenetic aberrations in sporadic renal cell carcinoma (RCC). In addition, a majority of RCCs have loss of heterozygosity (LOH) of the Von Hippel-Lindau (VHL) gene located at chromosome band 3p25. Patients who inherit a germline mutation of the VHL gene can develop multifocal RCCs and other solid tumors, including malignancies of the pancreas, adrenal medulla, and brain. VHL tumors follow the two-hit model of tumorigenesis, as LOH of VHL, a classic tumor suppressor gene, is the critical event in the development of the neoplastic phenotype. In an attempt to define the cytogenetic aberrations from early tumors to late RCC further, we applied spectral karyotyping (SKY) to 23 renal tumors harvested from 6 unrelated VHL patients undergoing surgery. Cysts and low-grade solid lesions were near-diploid and contained 1,2 reciprocal translocations, dicentric chromosomes, and/or isochromosomes. A variety of sole numerical aberrations included gains of chromosomes 1, 2, 4, 7, 10, 13, 21, and the X chromosome, although no tumors had sole numerical losses. Three patients shared a breakpoint at 2p21,22, and three others shared a dicentric chromosome 9 or an isochromosome 9q. In contrast to the near-diploidy of the low-grade lesions, a high-grade lesion and its nodal metastasis were markedly aneuploid, revealed loss of VHL by fluorescence in situ hybridization (FISH), and contained recurrent unbalanced translocations and losses of chromosome arms 2q, 3p, 4q, 9p, 14q, and 19p as demonstrated by comparative genomic hybridization (CGH). By combining SKY, CGH, and FISH of multiple tumors from the same VHL kidney, we have begun to identify chromosomal aberrations in the earliest stages of VHL-related renal cell tumors. Our current findings illustrate the cytogenetic heterogeneity of different VHL lesions from the same kidney, which supports the multiclonal origins of hereditary RCCs. Published 2001 Wiley-Liss, Inc. [source]


Viral load and physical status of human papillomavirus (HPV) 18 in cervical samples from female sex workers infected with HPV 18 in Burkina Faso

JOURNAL OF MEDICAL VIROLOGY, Issue 10 2009
Audrey Damay
Abstract Viral DNA load and physical status might be predictive of either high-grade cervical lesions or disease progression among women infected by human papillomavirus (HPV) 16, but these virological markers have rarely been studied in HPV 18 infections. The relationships between HPV 18 DNA load, viral genome physical status and cervical squamous intraepithelial lesions were analyzed among female sex workers infected with HPV18 in Burkina Faso. HPV 18 E2 and E6 genes were quantitated by real-time PCR. Among 21 women infected with HPV 18, 67% of whom were HIV-1-seropositive, 11 (52.4%) had a normal cytology, 8 (38.1%) had low-grade squamous intraepithelial lesions, and 2 (9.5%) had high-grade squamous intraepithelial lesions. Total viral load and integrated viral load were higher in women with squamous intraepithelial lesions than in women with normal cytology (P,=,0.01 for both parameters). Total viral load and integrated viral load were higher in HIV-1-seropositive women than in those who were not infected with HIV (P,=,0.01, and P, 0.01, respectively). Total viral load or integrated viral load >1,000,copies/ng of DNA were more frequent in women with squamous intraepithelial lesions than in women with normal cytology (7/10 vs. 1/11; P,=,0.007) and in HIV-1-seropositive women (8/14 vs. 0/7 in HIV-uninfected women; P,=,0.02). Both HPV 18 DNA and integrated DNA loads might represent markers of cervical lesions. Prospective evaluations are needed to establish the value of these parameters to predict high-grade lesion or lesion progression. J. Med. Virol. 81:1786,1791, 2009. © 2009 Wiley-Liss, Inc. [source]


A CRITICAL LOOK AT PAP ADEQUECY: ARE OUR CRITERIA SATISFACTORY?

CYTOPATHOLOGY, Issue 2006
D.R. Bolick
Liquid based Pap (LBP) specimen adequacy is a highly documented, yet poorly understood cornerstone of our GYN cytology practice. Each day, as cytology professionals, we make adequacy assessments and seldom wonder how the criteria we use were established. Are the criteria appropriate? Are they safe? What is the scientific data that support them? Were they clinically and statistically tested or refined to achieve optimal patient care? In this presentation, we will take a fresh look at what we know about Pap specimen adequacy and challenge some of the core assumptions of our daily practice. LBP tests have a consistent, well-defined surface area for screening, facilitating the quantitative estimates of slide cellularity. This provides an unprecedented opportunity to establish reproducible adequacy standards that can be subjected to scientific scrutiny and rigorous statistical analysis. Capitalizing on this opportunity, the TBS2001 took the landmark step to define specimen adequacy quantitatively, and set the threshold for a satisfactory LBP at greater than 5,000 well visualized squamous epithelial cells. To date, few published studies have attempted to evaluate the validity or receiver operator characteristics for this threshold, define an optimal threshold for clinical utility or assess risks of detection failure in ,satisfactory' but relatively hypocellular Pap specimens. Five years of cumulative adequacy and cellularity data of prospectively collected Pap samples from the author's laboratory will be presented, which will serve as a foundation for a discussion on ,Pap failure'. A relationship between cellularity and detection of HSIL will be presented. Risk levels for Pap failure will be presented for Pap samples of different cellularities. The effect of different cellularity criterion on unsatisfactory Pap rates and Pap failure rates will be demonstrated. Results from this data set raise serious questions as to the safety of current TBS2001 adequacy guidelines and suggest that the risk of Pap failure in specimens with 5,000 to 20 000 squamous cells on the slide is significantly higher than those assumed by the current criteria. TBS2001 designated all LBP to have the same adequacy criterion. Up to this point, it has been assumed that ThinPrep, SurePath, or any other LBP would be sufficiently similar that they should have the same adequacy criteria. Data for squamous cellularity and other performance characteristics of ThinPrep and SurePath from the author's laboratory will be compared. Intriguing data involving the recently approved MonoPrep Pap Test will be reviewed. MonoPrep clinical trial data show the unexpected finding of a strong correlation between abundance of endocervical component and the detection of high-grade lesions, provoking an inquiry of a potential new role for a quantitative assessment of the transition zone component. The current science of LBP adequacy criteria is underdeveloped and does not appear to be founded on statistically valid methods. This condition calls us forward as a body of practitioners and scientists to rigorously explore, clarify and define the fundamental nature of cytology adequacy. As we forge this emerging science, we will improve diagnostic performance, guide the development of future technologies, and better serve the patients who give us their trust. Reference:, Birdsong GG: Pap smear adequacy: Is our understanding satisfactory? Diagn Cytopathol. 2001 Feb; 24(2): 79,81. [source]


Comparison of the sensitivity of conventional cytology and the ThinPrep Imaging System for 1,083 biopsy confirmed high-grade squamous lesions,

DIAGNOSTIC CYTOPATHOLOGY, Issue 5 2010
C.T. (A.S.C.), C.T. (I.A.C.), J. A. Halford B.App.Sc.
Abstract Liquid-based cytology continues to be utilized as an adjunct to conventional cytology in most Australian laboratories, even though a direct-to-vial ThinPrep protocol has been introduced in many countries with established cervical screening programs. Manual screening of ThinPrep slides has been widely practiced for more than 10 years and the recent introduction of the ThinPrep Imaging System (TPI) has been reported as being more sensitive than the conventional smear (CS) in the identification of high-grade cervical disease. We report our experience with ThinPrep Imaging since its introduction into our routine gynecological cytology service. 87,284 split sample pairs reported using the Imaging System demonstrated a decrease in unsatisfactory reports (3.65% for CS and 0.87% for TPI) and an increase in possible high grade and definite high-grade squamous reports (1.57% for CS and 1.62% for TPI). For 1,083 biopsy confirmed high-grade lesions, the correct diagnosis of high grade or possible high-grade squamous disease was made on the ThinPrep imaged slide in 61.0% (661/1,083) of cases and on the CS in 59.4% (643/1,083). This was not statistically significant. When all abnormalities identified on cytology were considered, including possible low grade and definite low-grade abnormalities, the difference in sensitivity for Thinprep imaged slides of 96.0% (1,040/1,083) and CSs of 91.6% (992/1,083) was statistically significant. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source]


ASC-US and high-risk HPV testing: Performance in daily clinical practice

DIAGNOSTIC CYTOPATHOLOGY, Issue 11 2006
Suzanne M. Selvaggi M.D.Article first published online: 13 OCT 200
Abstract Data are beginning to accrue on high-risk HPV DNA testing in patients with ASC-US on cervical cytology. We report on our experience at the University of Wisconsin Hospital and Clinics. From February 2002 through December 31, 2005 (3 yr, 11 mo), the cytopathology laboratory processed 49,599 Pap Tests, of which 1,792 (3.6%) were diagnosed as ASC-US. Six hundred and seventy two (37.5%) of these cases were processed for high-risk HPV genotypes using the Digene Hybrid® Capture II method. Of these cases, 266 (39.6%) were positive for high-risk HPV genotypes, 11 (1.6%) were equivocal, and 395 (58.8%) were negative. Biopsy follow-up was available for 127 (47.7%) of the 266 cases, of which 66 (52%) were negative, 46 (36.2%) showed CIN I, 9 (7.1%) were CIN II, and 6 (4.7%) were CIN III. Of the remaining 139 (52.3%) cases, 86 (62%) had follow-up Pap Tests, of which 57 (66.3%) were negative, 15 (17.4%) were ASC-US, 12 (15%) were low-grade squamous intraepithelial lesions, and 2 (2.3%) were high-grade squamous intraepithelial lesions; 53 (38.1%) were lost to follow-up. In combination, 90 (42.25%) of the 213 cases with follow-up showed atypia or above after a diagnosis of ASC-US; of which 58 (64%) were low-grade lesions and 17 (19%) were high-grade lesions. Our laboratory's reported high-risk HPV positivity is comparable to recent reports in the literature on its use in daily clinical practice. In addition, cervical abnormalities were found in a significant proportion of the cases. Diagn. Cytopathol. 2006;34: 731,733. © 2006 Wiley-Liss, Inc. [source]


Identification of novel DNA methylation markers in cervical cancer,

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2008
Hung-Cheng Lai
Abstract Testing for DNA methylation has potential in cancer screening. Most previous studies of DNA methylation in cervical cancer used a candidate gene approach. The aim our study was to identify novel genes that are methylated in cervical cancers and to test their potential in clinical applications. We did a differential methylation hybridization using a CpG island (CGI) microarray containing 8640 CGI tags to uncover methylated genes in squamous cell carcinomas (SCC) of the uterine cervix. Pooled DNA from cancer tissues and normal cervical swabs were used for comparison. Methylation-specific polymerase chain reaction, bisulfite sequencing and reverse transcription polymerase chain reaction were used to confirm the methylation status in cell lines, normal cervices (n = 45), low-grade lesions (n = 45), high-grade lesions (HSIL; n = 58) and invasive squamous cell carcinomas (SCC; n = 22 from swabs and n = 109 from tissues). Human papillomavirus (HPV) was detected using reverse line blots. We reported 6 genes (SOX1, PAX1, LMX1A, NKX6-1, WT1 and ONECUT1) more frequently methylated in SCC tissues (81.5, 94.4, 89.9, 80.4, 77.8 and 20.4%, respectively) than in their normal controls (2.2, 0, 6.7, 11.9, 11.1 and 0%, respectively; p < 0.0001). Parallel testing of HPV and PAX1 methylation in cervical swabs confers an improved sensitivity than HPV testing alone (80% vs. 66%) without compromising specificity (63% vs. 64%) for HSIL/SCC. Testing PAX1 methylation marker alone, the specificity for HSIL/SCC is 99%. The analysis of these novel DNA methylations may be a promising approach for the screening of cervical cancers. © 2008 Wiley-Liss, Inc. [source]


Immunocytochemistry in liquid-based cervical cytology: Analysis of clinical use following a cross-sectional study

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2006
Shaira Sahebali
Abstract Cytological screening for cervical cancer is hampered by imperfect sensitivity and low inter-observer reproducibility. Human papillomavirus (HPV) testing lacks specificity as a primary screening method. Studies indicate that immunocytochemical detection of alterations caused by HPV in the host cells can optimise screening. Here, the potential of p16INK4a (cyclin-dependent kinase inhibitor p16) and MIB-1 (Ki-67 proliferation marker) as adjunct molecular markers for cervical lesions was investigated in a prospective, cross-sectional study of 500 samples in the framework of opportunistic screening in Flanders, Belgium. A consecutive series of 200 samples and 100 samples from the cytological categories ASC, LSIL and HSIL were investigated. Surepath samples were interpreted according to the Bethesda 2001 reporting system. HPV testing was done with MY09/MY11 consensus PCR. Immunocytochemistry for p16INK4a and MIB-1 was performed with an automated staining protocol. The number of immunoreactive cells/1,000 cervical cells was assessed. There was a higher mean number of p16INK4A and MIB-1 immunoreactive cells/1,000 cells in HSIL (4.06 ± 1.93 and 11.13 ± 2.83, respectively) compared to other cytological categories. Both markers showed a large spread in counts, for all categories. In cases of HSIL without immunoreactive cells for either marker, low cellularity and long-term storage in water were often the cause of false negativity. This study confirms that positive staining for p16INK4a and MIB-1 is highly correlated with presence of high-grade lesions. These markers could be used as adjuncts to increase the sensitivity of cytological screening as well as the specificity of the HPV test. However, clear methodological standards are needed for optimal performance of immunocytochemistry in a clinical setting. © 2005 Wiley-Liss, Inc. [source]


Human papillomavirus infection and cervical abnormalities in Nairobi, Kenya, an area with a high prevalence of human immunodeficiency virus infection

JOURNAL OF MEDICAL VIROLOGY, Issue 5 2008
Rika Yamada
Abstract Human papillomavirus (HPV) infection and cervical abnormalities, and their association with human immunodeficiency virus (HIV) infection were studied in 488 women who visited a health center in Nairobi. PCR-based HPV and cervical cytology tests were carried out on all participants, and peripheral CD4+ T cells and plasma HIV RNA were quantitated in HIV positive women. HIV were positive in 32% (155/488) of the women; 77% of these were untreated, and the others had been treated with anti-retroviral drugs within 6 months. Cervical HPV infection was detected in 17% of HIV negative and 49% of HIV positive women. Low-grade squamous intraepithelial lesions were observed in 6.9% of HIV negative and 21% of HIV positive women, while high-grade squamous intraepithelial lesions and cancer were seen in 0.6% and 5.8%, respectively. Multivariate analysis revealed that HIV and HPV infections were associated with each other. Cervical lesions were significantly associated with high-risk HPVs and with HIV infection, depending on HPV infection. HPV infection increased in accordance with lower CD4+ T cell counts and higher HIV RNA levels, and high-grade lesions were strongly associated with high-risk HPV infection and low CD4+ T cell counts. Immunosuppression as a result of HIV infection appears to be important for malignant progression in the cervix. Nationwide prevention of HIV infection and cervical cancer screening are necessary for the health of women in this area. High-risk HPV infection and low CD4+ T cell counts are the risk factors for cervical cancer. J. Med. Virol. 80:847,855, 2008. © 2008 Wiley-Liss, Inc. [source]


Morphological spectrum of cyclin D1-positive mantle cell lymphoma: Study of 168 cases

PATHOLOGY INTERNATIONAL, Issue 10 2001
Yasushi Yatabe
Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium, large (13.2%) and large (6.6%) cells. Pleomorphic and blastic / blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia / small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features. [source]


Should liquid-based cytology be performed prior to colposcopy?

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2009
A comparison of the accuracy, cost in a tertiary referral setting, unsatisfactory rates
Objective:, To compare the use of liquid-based cytology (LBC) with conventional cytology (CC) in the assessment cervical intraepithelial neoplasia (CIN) prior to colposcopy. Design:, Retrospective Cohort Study. Methods:, Liquid-based cytology and CC findings were compared with colposcopic assessment and directed cervical biopsy in terms of sensitivity and specificity for high grade lesions only and for any abnormalities. The degree of correlation was sought. Secondary outcomes were unsatisfactory rate and cost. Results:, A total of 1961 women had colposcopy of whom 528 had cervical biopsy. LBC and CC have similar sensitivity and specificity for both high-grade lesions and any abnormalities. In comparison with cervical biopsy, LBC and CC sensitivity for high-grade disease was 89.1% and 88.6% respectively and for any abnormalities, the sensitivity was 86.6% and 87.0%. Specificity for high-grade disease was 83.1% and 84.7% and for any abnormalities, the specificity was 53.8% and 56.4%. The unsatisfactory rate was significantly lower in LBC 4.38% compared to 1.84% (P < 0.001). However, the use of LBC was associated with an additional cost of A$1496 for each unsatisfactory smear avoided. Conclusion:, In high prevalence setting, LBC showed no statistically significant difference in sensitivity and specificity from CC for the detection of CIN. A reduction in unsatisfactory smears was evident, but at significant additional cost. [source]


Comparison of three management strategies for patients with atypical squamous cells of undetermined significance, after six months delay: A three-year experience in an Iranian university hospital

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009
Fariba YARANDI
Background: A Pap test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5,10% of women with ASCUS harbour serious cervical disease. Methods: We screened 3619 women, who attended to Mirza Koochak Khan Hospital at Tehran University of Medical Sciences with Pap smears, of whom 100 returned with ASCUS. After six months, each subject underwent a standard cytology (conventional Pap smear), human papillomavirus (HPV) DNA testing (identifying high-risk HPV types with polymerase chain reaction) and colposcopy with multiple cervical biopsies. Results: Mean age was 44.09 ± 8.6 years. The estimated prevalence of cervical intraepithelial neoplasia (CIN) II or higher was 4%. When histologically verified high-grade lesions (, CIN II) were observed, the relative sensitivity of HPV DNA testing was 100% compared with conventional Pap smear, which performed 75% versus 100% relative sensitivity, respectively, using cytological diagnosis high-grade squamous intraepithelial lesion, or low-grade squamous intraepithelial lesion (LSIL) as the cut-off. Negative and positive predictive values (NPV and PPV) of Pap test were 98.9% and 100%. The NPV and PPV of HPV DNA testing were 100%. Conclusions: Although less complicated than colposcopy, the repeat Pap smear triage algorithm for ASCUS may underdiagnose some women with high-grade CIN, when compared with colposcopy. Considering the high sensitivity of HPV testing, it may be useful as an alternative to the current policy of six-month repeat cytology for women with ASCUS results. [source]


A randomised comparison of SurePath liquid-based cytology and conventional smear cytology in a colposcopy clinic setting

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2008
PH Sykes
Objective, The objective of this study was to compare the sensitivity of cervical cytology using conventional smears and SurePath liquid-based cytology (LBC). Design, Prospective randomised evaluation of diagnostic test. Setting, A single institution colposcopy clinic. Population, Women attending first visit colposcopy appointments were offered entry into the study. Methods, Cervical cytology samples from 913 women of age 16,75 years were randomly processed as SurePath LBC or conventional smears. Conventional smears were taken for 453 women and a SurePath LBC taken for 451 women. Cytology results were correlated with colposcopic findings and histology from colposcopic biopsies, treatment and follow up. Main outcome measures, To compare the sensitivity of SurePath LBC and conventional smears for histologically proven abnormality. Other outcome measures include a comparison of their sensitivity for high-grade abnormalities and their satisfactory rate. Results, Accounting for all randomised samples, there was a trend towards improved sensitivity for SurePath LBC (79.1 versus 73.7%, P = 0.1). However, excluding unsatisfactory cytology (and samples not taken) eliminated this trend; the sensitivity for both LBC and conventional smears for any epithelial abnormality was 81%. With a threshold of atypical squamous cells of uncertain significance (ASC-US), both SurePath LBC and conventional smears had a sensitivity of 92% for high-grade lesions. SurePath LBC was less likely to be reported as unsatisfactory (2.7 versus 9.1%, P < 0.0001). Conclusions, In this context, with a threshold of ASC-US, both SurePath LBC and conventional smears offer high sensitivity for the detection of CIN2/3, but SurePath LBC is less likely to be reported as unsatisfactory. [source]


Anaplasia and Grading in Medulloblastomas

BRAIN PATHOLOGY, Issue 3 2003
Charles G. Eberhart;
The variable clinical outcomes of medulloblastoma patients have prompted a search for markers with which to tailor therapies to individuals. In this review, we discuss clinical, histological and molecular features that can be used in such treatment customization, focusing on how histopathological grading can impact both patient care and research on the molecular basis of CNS embryonal tumors. Medulloblastomas span a histological spectrum ending in overtly malignant large cell/anaplastic lesions characterized by increased nuclear size, marked cytological anaplasia, and increased mitotic and apoptotic rates. These "high-grade" lesions make up approximately one quarter of medulloblastomas, and recur and metastasize more frequently than tumors lacking anaplasia. We believe anaplastic change represents a type of malignant progression common to many medulloblastoma subtypes and to other CNS embryonal lesions as well. Correlation of these histological changes with the accumulation of genetic events suggests a model for the histological and molecular progression of medulloblastoma. [source]


DNA ploidy compared with human papilloma virus testing (Hybrid Capture II) and conventional cervical cytology as a primary screening test for cervical high-grade lesions and cancer in 1555 patients with biopsy confirmation

CANCER, Issue 2 2006
Martial Guillaud PhD
Abstract BACKGROUND. Because 80% of cervical cancers arise in low-resource settings, many inexpensive strategies are being tested. In that spirit, the authors are testing large-scale genomic or DNA ploidy measurements as an inexpensive and semiautomated strategy. METHODS. Patients entered either a screening or diagnostic study of several optical technologies: quantitative cytology, quantitative histopathology, and fluorescence and reflectance spectroscopy using a point probe, a multispectral digital colposcope, or a combination of the two. We calculated sensitivities, specificities, positive and negative predictive values, and their confidence interval testing conventional cytology, Hybrid Capture (HC) II testing, and DNA ploidy measured on the Feulgen-stained quantitative Pap smear. RESULTS. The current investigation reports on 1555 patients for whom colposcopically directed biopsies were read 3 times by study pathologists. The final histopathologic diagnosis was high grade (cervical intraepithelial neoplasia [CIN] 2, CIN 3, carcinoma in situ [CIS], and cancer) in 16% of patients. Using high-grade squamous intraepithelial lesions (SILs) histopathology as the threshold and gold standard, the sensitivity and specificity, respectively, were: 0.47 and 0.96 for conventional cytology, 0.91 and 0.80 for HC II, and 0.59 and 0.93 for DNA ploidy. The positive and negative predictive values (PPV, NPV) for conventional cytology were 0.70 and 0.90, 0.46 and 0.98 for HC II, and 0.63 and 0.92 for DNA ploidy. CONCLUSIONS. DNA ploidy shows comparable sensitivity, specificity, PPV, and NPV values to conventional cytology and HC II. Unlike conventional cytology, DNA ploidy is semiautomated and can be performed in less than 8 hours. Cost effectiveness studies are under way, but in the authors' laboratory DNA ploidy is inexpensive. Cancer 2006. © 2006 American Cancer Society. [source]