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Objectives: To examine data correlating high-risk human papillomavirus (hrHPV) results in patients with both low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) cytology findings (LSIL-H) with follow-up histopathology., Methods: A total of 494 LSIL-H ThinPrep (Hologic, Marlborough, MA) cases with hrHPV testing were identified. Histopathologic follow-up was available in 347 patients., Results: Among 347 patients with follow-up histopathology after LSIL-H cytology and hrHPV testing, 90.5% tested hrHPV positive. Cervical intraepithelial neoplasia (CIN) 2/3 was diagnosed in 29.4% and CIN 1 in 53.6%. CIN 2/3 was diagnosed in significantly more patients with hrHPV-positive LSIL-H than following hrHPV-negative LSIL-H results. Compared with published institutional data, LSIL-H had significantly lower hrHPV and histopathologic CIN 2/3+ rates (90.5% and 29.4%, with no cervical cancers) than high-grade squamous intraepithelial lesion (HSIL) (95.7% and 70.5%, with 2.4% cervical cancers) but higher rates than LSIL (80.2% and 12.9%) or atypical squamous cells/cannot exclude HSIL (ASC-H) (54.3% and 17.2%). Whereas CIN 2/3 detection rates were similar in HPV-positive LSIL-H and HPV-positive ASC-H, CIN 2/3 findings were more likely with HPV-negative LSIL-H than with HPV-negative ASC-H., Conclusions: LSIL-H is a unique category of cytologic abnormality associated with distinctive hrHPV and CIN 2/3+ diagnostic rates.

Background: Studies of the performance of the automated FocalPoint Guided Screening (FPGS) imaging system in gynecologic cytology screening relative to manual screening have yielded conflicting results. In view of this uncertainty, a validation study of the FPGS was conducted before its potential adoption in 2 large laboratories in Ontario., Methods: After an intense period of laboratory training, a cohort of 10,233 current and seeded abnormal slides were classified initially by FPGS. Manual screening and reclassification blinded to the FPGS results were then performed. Any adequacy and/or cytodiagnostic discrepancy between the 2 screening methods subsequently was resolved through a consensus process (truth). The performance of each method's adequacy and cytodiagnosis vis-a-vis the truth was established. The sensitivity and specificity of each method at 4 cytodiagnostic thresholds (atypical squamous cells of undetermined significance or worse [ASC-US+], low-grade squamous intraepithelial lesion or worse [LSIL+], high-grade squamous intraepithelial lesion or worse [HSIL+], and carcinoma) were compared. The false-negative rate for each cytodiagnosis was determined., Results: The performance of FPGS in detecting carcinoma, HSIL+, and LSIL+ was no different from the performance of manual screening, but the false-negative rates for LSIL and ASC-US were higher with FPGS than with manual screening., Conclusions: The results from this validation study in the authors' laboratory environment provided no evidence that FPGS has diagnostic performance that differs from manual screening in detecting LSIL+, HSIL+, or carcinoma., (Copyright © 2012 American Cancer Society.)

Background: The 2001 Bethesda System for gynecologic cervical cytology reporting classifies squamous intraepithelial lesions into low-grade (LSIL) and high-grade (HSIL) lesions. An intermediate term, "low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion (LSIL-H)," has been used in a small percentage of LSIL cases. To the authors' knowledge, little is known regarding the human papillomavirus (HPV) status in patients with LSIL-H., Methods: A total of 808 SurePath specimens obtained between December 2009 and April 2011 were tested for 40 HPV genotypes using DNA microarray, followed by a confirmatory DNA sequencing assay., Results: The infection rate for high-risk HPV in women with LSIL-H (92%) was strikingly close to that for women with HSIL (91%), which was higher than that for those with LSIL (74%); atypical squamous cells, cannot rule out high-grade lesion (ASC-H) (78%); or LSIL and ASC-H combined (74%). HPV type 16, the most common carcinogenic HPV genotype, was detected in 36% of women with LSIL-H, which was significantly higher than that in women with LSIL and ASC-H combined (13.8%), but less than that in women with HSIL (44.6%). Patients with LSIL-H and HSIL had similar infection rates for low-risk/intermediate-risk HPV genotypes, which were lower than those in LSIL or LSIL and ASC-H combined., Conclusions: Women found to have LSIL-H on a Papanicolaou test appear to have a unique HPV distribution pattern that clearly differs from LSIL and is comparable to that for HSIL, suggesting an increased risk of high-grade lesions over that of women with LSIL. Recognizing LSIL-H as an independent diagnostic category may help in the early identification of the high-risk subgroup that may require a management algorithm comparable to that for patients with HSIL. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society., (Copyright © 2012 American Cancer Society.)

Objective: To analyze the correlation and accuracy between Reid's colposcopic index (RCI) and histologic results from colposcopically directed biopsy (CDB) in differentiating high-grade squamous intraepithelial lesion (HSIL) from low-grade squamous intraepithelial lesion (LSIL)., Materials and Method: A retrospective analysis of medical records of women who had abnormal Pap smear and underwent colposcopy, RCI scoring and CDB from January 1st, 2003 to December 31st, 2006 at Rajavithi Hospital was conducted., Results: One hundred women were included in the present study. Compared with histological diagnosis from CDB, accuracy for four colposcopic criteria: margin pattern, color, vascular pattern and iodiness staining were 73.0%, 79.0%, 75.0% and 69.2%, respectively. Combining these variables into RCI showed 89.0% overall accuracy. Color and vascular pattern showed a good agreement with histologic results from CDB (Kendall's tau C = 0.68 and 0.63; p < 0.05). Overall, RCI yielded a good agreement (Kendall's tau C = 0.66; p < 0.05)., Conclusion: RCI yields a good correlation with histology from CDB and it has high accuracy in differentiating HSIL from LSIL.

Objective: To evaluate the histopathology of women who had "atypical squamous cells of undetermined significance" (ASC-US) on cervical cytology in a region with high incidence of cervical cancer., Material and Method: Retrospective case-record review of 254 women with ASC-US cytology undergoing colposcopic examination at Nakornping Hospital between October 2003 and September 2007., Results: Of the 254 patients who had ASC-US smears underwent colposcopic and histopathologic evaluation. The mean age was 45.3 years (range, 18-72 years). The histologic diagnoses, obtained from colposcopically directed biopsy or endocervical curettage or loop electrosurgical excision procedure or cold knife conization after initial colposcopy, showed that 47 (18.5%) women had histologically confirmed high-grade lesions and 20 (7.9%) women had invasive cancers. There was no statistically significant difference in the incidence of high-grade or invasive lesions between who were 50 years old or more and those who were younger (50.0% and 50.5%, respectively, p = 0.39)., Conclusion: Reporting ASC-US cytology in our population is obviously associated with significant cervical pathology, particularly invasive cancer that is possible at a rate higher than previously reported. Women who have ASC-US smears should therefore be referred for immediate colposcopy regardless of age.

We undertook this study to assess the characteristics of smears with features intermediate between high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesion (ISIL). We also wanted to determine how these smears correlate with high risk biopsy diagnosis and to compare this with the biopsy correlation of LSIL and HSIL. Seventy-four squamous intraepithelial lesion (SIL) smears were identified as intermediate-grade SIL smears taken at colposcopy in a 1 year period. They were correlated with concurrent colposcopically guided biopsies. Thirty-five percent of cases with intermediate-grade SIL smears had a biopsy diagnosis of moderate dysplasia or higher as compared with 12% for LSIL 74% for HSIL. This confirmed our hypothesis that intermediate-grade SIL smears have a rate of biopsy diagnosis of moderate dysplasia or higher intermediate to that of LSIL and HSIL.

Objective: This study evaluated the impact of the Bethesda System (TBS) 2001 in reporting of atypical glandular cells (AGC) when using conventional Pap smears (CS) and liquid-based cytology preparations (LBC)., Study Design: Follow-up information for all atypical glandular cells of undetermined significance (AGUS)/ AGC cases encountered in Queen Mary Hospital from July 2000 to June 2004 was analyzed. The difference in percentages associated with certain end points when using different reporting systems and preparation methods were compared. The age trends and time interval between cytologic diagnosis and detection of positive end points were studied., Results: More than half of these cases turned out to be "negative." The majority with "negative" end points belonged to the "not otherwise specified" (NOS) groups (including atypical endometrial cells) in TBS 2001. The connotation of "favor neoplastic" carried a high positive predictive value for significant lesions. Most of the significant outcomes were discovered within the subsequent 6 months. A decreased reporting of "AGC, NOS" and an increased reporting of "atypical endocervical cells, NOS" were noted when using LBC., Conclusion: Subcategorization of AGC in TBS 2001 according to cellular origin and risk of malignancy, which is further enhanced by application of LBC, is useful.

Objective: In the current study, we explore the diagnostic parameters and pitfalls in the follow-up of 123 cases of Pap smears diagnosed as high-grade atypical squamous cells (ASC-H) at our institution., Study Design: A computer database search was performed from the archives of the Ottawa Hospital Cytopathology Service for cases diagnosed with ASC-H between January 2003 and July 2005., Results: Follow-up of the 123 cases of ASC-H showed high grade squamous intraepithelial lesion (HSIL) in 73 patients (59.4%), low grade squamous intraepithelial lesion (LSIL) in 11 (8.9%), immature squamous metaplasia in 23 (18.7%), reactive squamous cell changes in 12 (9.8%), benign glandular lesions (endocervical atypia, degenerated glandular cells) in 2 (1.6%) and atrophy in 2 (1.6%). In our study, 83 patients were younger than 40 years (67.4%), with biopsy-proven HSIL found in 54 patients (65.1%). The remaining 40 patients (32.6%) were older than 40 years of age, and follow-up biopsies showed HSIL in 19 patients (47.5%)., Conclusion: In our study, 59.4% of the cases that were diagnosed cytologically as ASC-H were found to have HSIL on subsequent biopsies. This correlation was stronger in patients below the age of 40 years (65.1% vs. 47.5%). The cytopathologic feature most strongly associated with HSIL was the presence of coarse nuclear chromatin (84%).

We evaluated the impact of the Bethesda System (TBS) 2001 in cytology reporting of atypical squamous cells (ASC) when using conventional Pap smears and liquid-based cytology preparations (LBC). Follow-up information for all ASC cases encountered in Queen Mary Hospital, Hong Kong, China, from July 2000 to June 2004 (using TBS 1991 in the first 2-year period and TBS 2001 in the second) was analyzed. Among 4, 089 ASC cases studied, more than 50% had negative follow-up; this percentage was lower with TBS 2001. The percentage of ASC cases with a low-grade cervical intraepithelial neoplasia (CIN) end point was higher with TBS 2001, especially after application of LBC. There was also a decreasing trend of having this low-grade CIN end point with advancing age. Most clinically significant outcomes occurred after 6 months and before 1 year post-ASC diagnosis. With TBS 2001, more than 50% of ASC, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) were associated with high-grade CIN on follow-up. TBS 2001 improves the positive predictive value of ASC for clinically significant lesions. Introduction of dichotomous subcategorization of ASC is relevant, with ASC-H associated with a much higher risk of subsequent high-grade squamous lesions.

We compared the overall ASC rate and the outcomes for women with different categories of ASC before and after TBS 2001 to evaluate the impact of TBS 2001. Our laboratory reported ASC in four subcategories before TBS 2001; ASC, favor reactive (ASC-R), favor low-grade squamous intraepithelial lesion (SIL) (ASC-L), undetermined significance (ASC-US), and ASC-H. Since the implementation of TBS 2001, we have been reporting ASC as ASC-US and ASC-H. After TBS 2001, our ASC rate decreased from 6.2% to 4% (P < 0.0001). Before TBS 2001, ASC-R carried the same risk as ASC-US for underlying condyloma/CIN 1. Moreover, ASC-R was rarely associated with CIN 2 or 3. Before TBS 2001, ASC-H captured more low-grade (condyloma/CIN 1) and less high-grade (CIN 2, 3, and SCC) lesions compared to after TBS 2001. More women with ASC-H after TBS 2001 underwent colposcopy (80% vs. 71%, P < 0.05). Twenty-two percent of women with ASC-H required 2-4 colposcopies to identify the high-grade lesion. Our results confirm that consistent application of TBS 2001 terminology for ASC reduces the ASC rate, and better identifies women at high risk for CIN 2, 3, and SCC. In addition, ASC-H requires very close clinical follow-up as a significant percentage of women require more than one colposcopy to identify the high-grade lesion.

Background: Transmission over the Internet of low-resolution images acquired by automated screening of cervical cytology specimens has the potential to provide remote interpretation and, hence, centralization of a cytology workforce., Methods: Liquid-based cervical cytology slides were scanned using the FocalPoint(R) System. Ten black-and-white images that had the greatest probability of containing abnormality were acquired from each of 32 reference slides (16 negative samples, 3 samples of atypical squamous cells of uncertain significance, 5 samples of low-grade squamous intraepithelial lesions [LSIL], 5 samples of high-grade squamous intraepithelial lesions [HSIL], 1 adenocarcinoma in situ sample, and 2 carcinoma samples) and were transmitted as e-mail attachments in JPEG format to remote reading stations. The slides were interpreted independently by two pathologists and were assigned to either of two groups: 1) suspicious for >or=HSIL or 2)

Recent revisions of the Bethesda System (TBS III) did not modify the original two-tiered low-grade and high-grade squamous intraepithelial lesion (LSIL/HSIL) terminology and continued to offer the option of subclassifying HSIL into moderate dysplasia/cervical intraepithelial neoplasia (CIN II) and severe dysplasia/CIN III. The purpose of this study is to evaluate the significance of the HSIL moderate dysplasia/CIN II subclassification and the causes of Pap test-biopsy discordance for this subclassification. HSIL/moderate dysplasia/CIN II Pap tests were identified from the University of California Davis Medical Center laboratory file for a 5-yr period (1997-2001) and correlated with follow-up cervical biopsies. Cervical biopsies with CIN II diagnoses were identified from the laboratory file for the same time period, and correlated with their preceding Pap test. Discordant Pap test-biopsy pairs from either group were reviewed by two pathologists for the following causes for discordance: cytologic overcall or undercall, biopsy overcall or undercall, and sampling error or possible lesion regression. During the review period, 161 of 378 total HSIL Pap tests had a HSIL/CIN II result (42%), and 81/161 (50%) had a follow-up cervical biopsy. 38/81 (47%) were concordant, and 43 (53%) were discordant; 39/43 discordant cases had both Pap test and biopsy slides available for review. CIN I was the most common discordant biopsy diagnosis. Sampling error was the most common cause of discordance and was three times more common than the other causes; 536 CIN cervical biopsies with CIN were identified in the laboratory files during this review period, and 108/536 (20%) received a diagnosis of CIN II. Sixty-seven of 108 (62%) had a preceding Pap test result available; 32 of the 67 (48%) had a concordant preceding Pap test with a HSIL/CIN II result, and 35 (52%) were discordant; 32/35 discordant cases had both Pap test and biopsy slides available for review. LSIL was the most common discordant Pap test diagnosis. Sampling error was also the most common cause of discordance, and was also three time more frequent than any other cause for discordance. HSIL/CIN II is a meaningful subclassification in our laboratory. We support the TBS III recommendation for optional subclassification of HSIL and suggest that individual laboratories may wish to monitor use of this subclassification through internal correlation studies., (Copyright 2004 Wiley-Liss, Inc.)

Objectives: The cytologic report written by a cytopathologist on the basis of smears from the cervix and cervical canal ought to give detailed and worthwhile information which allows making appropriate diagnostic and therapeutic decisions. The diagnosis of atypical cells of unspecified importance (ASCUS and AGUS) ought to have clinicians to carry out further diagnostic histopathologic procedures in order to explain the pathologic character of processes going on in the female reproductive organ. This is because such pathological states may as well spell could mean reactive, preinvasive as neoplastic changes of invasive character., Design: This problem has led to carry out a research in order to examine the proliferative potential of cells in cytological smears (Ki-67, AgNORs) and to answer whether this potential allows us to qualify atypical cells as changes of reactive or neoplastic type., Materials: In our study there were estimated 97 cases of cytological smears from the cervix and cervical canal. In this paper, immunohistochemical methods, and staining techniques developed by Ploton et al. in the detection of AgNORs and in the examination of Ki-67 antigen were used., Conclusions: 1. The average number of AgNORs in cell nucleus was highest in ASCUS cells and exceedingly higher in CIN 1 and CIN 3.2. The areal ratio of AgNORs to that of the cell nucleus was highest in HSIL and cancer cells, least in ASCUS. 3. In ASCUS and LSIL, AgNORs were minute and scattered whereas they were large and centrally located in HSIL and cancer cells., Results: We found that analysis of AgNORs makes easier the differentiation of ASCUS and LSIL cells from HSIL and neoplastic ones according to the classification system of Bethesda.

Objective: A new terminology for cytologic diagnosis of cervical lesions has been introduced by Bethesda System. This includes: 1) Atypical squamous cells of undetermined significance (ASCUS), 2) Low-grade squamous intraepithelial lesion (LSIL), 3) High-grade squamous intraepithelial lesion (HSIL), 4) squamo-cellular carcinoma. The aim of this study was to assess the correlation between the colpocytologic test (Pap psmear), the histologic response and colposcopy., Methods: We re-examined the cytologic results of 447 patients who underwent routine cytologic tests, with a diagnosis of various grades of atypia, from ASCUS to HSIL. A histologic test was carried out on a colposcopic basis in 210 cases and cytologic results were correlated with the histologic and colposcopic pictures., Results: For ASCUS the histology was positive in 19.1% (31/163) of cases and negative in 10.4% of the colposcopically positive cases (17/163), while in the remaining 70.5% (115/163) the colposcopy resulted negative. In LSIL with the presence of human papillomavirus (HPV) the histologic findings, confirmed the cytologic result in 35.8% (48/134) while in the group of cervical intraepithelial neoplasia (CIN I) results corresponded in 40.6% (41/101). In high squamous intraepithelial lesions there was an histologic confirmation in 59.2% (29/49)., Conclusions: The data obtained indicate an increase in positive histology results from the types of low grade (ASCUS-LSIL) to those of a high grade (HSIL). Our results indicate that the presence of ASCUS should be assessed colposcopically and histologically, where indicated.