Value of histiocyte detection in Pap smears for predicting endometrial pathology. An institutional experience

OBJECTIVE: To determine the clinical implications of the finding of histiocytes in Pap smears in 1 patient population. STUDY DESIGN: The medical records and Pap smears which the presence of histiocytes was mentioned in the diagnosis between August 1996 and August 2001 were reviewed in conjunction with follow-up surgical findings. The positive predictive value (PPV) for significant endometrial pathology for the isolated finding of histiocytes on Pap smear was determined. RESULTS: Of the 238,225 women screened over a 60-month period, 325 were reported to have histiocytes in their Pap smears. Of them, 238 (73.2%) had subsequent endometrial sampling, hysterectomy or both, and follow-up Pap smears. Two hundred seven smears (87%) failed to disclose endometrial pathology. Thirty-one cases (13%) resulted in significant histopathologic findings, including 12 uterine malignancies, 8 endocervical polyps, 7 endometrial polyps, 2 submucosal leiomyomata, 1 simple hyperplasia without atypia and 1 case of tamoxifen-related changes. Upon review of the clinical records, 58% (18/31) of those patients had other significant clinical and/or cytologic findings. Five of the 18 patients (27.8%) had associated postmenopausal bleeding, 11 had additional abnormal Pap smear findings (atypical glandular cells, 6/18, or 33.3%; endometrial cells, 5/18, or 27.8%), and another 2 had both postmenopausal bleeding and atypical glandular cells (2/18, or 11.1%). The PPV for significant uterine pathology for women with the isolated finding of histiocytes on a Pap smear was 5.5% and 60% with additional clinical and/or Pap smear findings. The PPV for endometrial cancer was 1.3% in women with the isolated finding of histiocytes on a Pap smear but 20% for women with histiocytes and additional clinical/or Pap smear findings. CONCLUSION: Based on the findings of this study and recently published data, we conclude that the isolated finding of increased histiocytes in the absence of postmenopausal bleeding, endometrial cells or atypical glandular cells on a Pap smear is a poor indicator of uterine disease.     

Bethesda 2001. Impact on the reporting of gynecologic cytology

OBJECTIVE: To examine the impact of implementing Bethesda 2001 in one laboratory. STUDY DESIGN: A computer search identified all cervicovaginal specimens evaluated between July 2001 and June 2002. Bethesda 2001 was implemented on January 1, 2002. The rates of specimen adequacy and the frequency of each diagnostic category 6 months before and 6 months after the implementation of Bethesda 2001 were compared. RESULTS: A total of 21,332 cervicovaginal specimens were evaluated during the study period. During the first 6 months, 10,695 specimens were examined; 40% were liquid-based preparations. During the next 6 months, 10,367 specimens were examined; 60% were liquid-based preparations. Prior to the implementation of Bethesda 2001, the percentages of each category were as follows: 74.99% within normal limits, 7.10% reactive/reparative cellular changes (R/R), 10.29% atypical squamous cells (ASC), 0.24% atypical glandular cells (AGC), 3.45% low grade squamous intraepithelial lesion (LSIL), 3.44% high grade squamous intraepithelial lesion (HSIL) and 0.73% unsatisfactory. In addition, 19.00% were classified as "satisfactory but limited by" (SBLB). Following the implementation of Bethesda 2001, the percentages of each category were as follows: 80.09% negative for intraepithelial lesion and malignancy including 6.94% with the qualifier R/R, 10.32% ASC, 0.27% AGC, 4.54% LSIL, 3.44% HSIL and 0.81% unsatisfactory. In addition, 17.40% were satisfactory with a quality indicator (SAT with QI). The incidence of reporting benign endometrial cells in patients over age 40 was the same for both periods. There was a significant decrease in the percentage of specimens classified as SAT with QI when compared to that of specimens classified as SBLB. A statistically significant increase in the percentage of specimens was noted in the category LSIL (P < or = .001) and satisfactory (.005) after implementing Bethesda 2001. No significant changes were noted in other categories. CONCLUSION: Our laboratory experienced some changes in the laboratory statistics of reporting gynecologic cytology after the implementation of Bethesda 2001. Continuous monitoring of reporting trends is indicated to clearly understand the impact of Bethesda 2001 on laboratory statistics.     

Clinical significance of atypical glandular cells by the 2001 Bethesda System in cytohistologic correlation

OBJECTIVE: To evaluate incidence, cytology findings and pathology outcome of atypical glandular cells (AGC) in Pap smears according to the 2001 Bethesda criteria. STUDY DESIGN: From 103,073 consecutive Pap smears, 113 (0.1%) AGC cases were identified. Of these, 91 (80%) had adequate histologic evaluation included in this study. RESULTS: Abnormal histology findings were seen in 38 patients (42%). Final pathology results revealed 14 endometrial adenocarcinomas, 5 endocervical adenocarcinomas, 1 cervical squamous cell carcinoma, 1 endometrial stromal sarcoma, 6 other malignancies, 4 endocervical adenocarcinomas in situ, 4 cases ofendometrial complex byperplasia, 1 case of endocervical glandular dysplasia and 2 cases of cervical intraepithelial neoplasia 3 with glandular involvement. Women with AGC, favor neoplasia, were more likely to have significant pathology than those with AGC, not otherwise specified, 74% vs. 33% (p = 0.002). Some characteristic background cytologic findings were also noticed in most cases of endometrial, fallopian tube and endocervical adenocarcinoma. CONCLUSION: A diagnosis of AGC is more clinically significant by the 2001 Bethesda System, especially the "AGC, favor neoplastic" category. Some background cytologic features are important because they are indicators of malignancy.     

Reporting endometrial cells in Papanicolaou smears of women age 40 and older: a qualifying educational note could prevent unnecessary follow-up biopsy

OBJECTIVE: To determine the impact of adding a qualifying educational note when exfoliated endometrial cells were present in the first half of the menstrual cycle. STUDY DESIGN: We identified all Pap smears that had endometrial cells in women > or = 40 years, between July and November, 2004. When endometrial cells were seen in the first half of menstrual cycle, it was stated that, "endometrial cells correlate with the menstrual history provided." We then attempted to determine if this qualifying comment had an impact on the decision to obtain a follow-up endometrial biopsy. RESULTS: A total of 325 women were identified. Of these, 51 (15.7%) had follow-up endometrial biopsy without clinical evidence of endometrial pathology, compared to a rate of 36.9% before implementation of the note (p < 0.0001). Biopsies were performed in 21 of 195 (10.8%) when the note indicated that endometrial cells correlated with menstrual history, compared to 30 of 130 (23%) in whom a different note was appended because endometrial cells were out of phase or patients were postmenopausal (p = 0.0032). Biopsies did not reveal significant endometrial pathology in any of the 51 patients. CONCLUSION: Adding an educational note when endometrial cells are reported in the first half of the menstrual cycle in women > or = 40 years may help reduce unnecessary biopsies.     

Diagnostic value of the thin-layer, liquid-based Pap test in endometrial cancer: a retrospective study with emphasis on cytomorphologic features

OBJECTIVE: To examine the diagnostic value (sensitivity and specificity of the ThinPrep Pap test in the detection of endometrial cancer and assess the morphologic features of endometrial cancer in ThinPrep tests. STUDY DESIGN: In a retrospective, case-controlled study, we identified 60 Pap slides performed within 12 months of the tissue diagnosis of endometrial carcinoma and 56 comparison slides from patients without known carcinoma. The slides were blindly reviewed by the authors without knowledge of the surgical diagnosis. An independent diagnosis was given for the tests based on 14 diagnostic criteria from the 2001 Bethesda System and 6 additional criteria proposed by the authors. RESULTS: The sensitivity of detecting endometrial carcinoma was 88.3% (95% CI 77.8-94.2%) and specificity was 87.5% (95% CI 76.4-93.8%). The positive likelihood ratio was 7.067 (95% CI 3.513-14.217) and negative likelihood ratio was 0.133 (95% CI 0.066-0.269). Enlarged nuclei and the presence of nucleoli in endometrial cells were the most reliable indicators of endometrial cancer or atypical endometrial cells. CONCLUSION: The ThinPrep Pap test has high sensitivity and specificity in detecting or suggesting the presence of endometrial cancer. Certain cytomorphologic features are helpful in distinguishing benign and malignant endometrial lesions.     

Follow-up study of atypical glandular cells in gynecologic cytology using conventional Pap smears and liquid-based preparations: impact of the Bethesda System 2001

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.     

Can older women be motivated to attend for their final Papanicolaou tests? The use of targeted and general personalised reminder letters

Background: Australian guidelines allow women to cease having Papanicolaou (Pap) tests at the age of 70, providing they have had two negative smears in the previous 5 years. In Victoria, a standard reminder letter system is in place and women receive one reminder letter 27 months after their last Pap test. Methods: A targeted letter informed by qualitative research was developed to specifically encourage older women to have a final Pap test. The Victorian Cervical Cytology Registry (VCCR) was used to identify 15,000 women aged 65–69 who had not had a Pap test for at least 3 years and up to 17 years. Women were randomly allocated to receive either no letter (control group), the targeted letter or a personally addressed general reminder letter. Results: At 11 weeks follow-up, 4.3% of women (CI 3.7–4.8%) who received the targeted letter had attended for a Pap test compared with 4.7% (CI 4.1–5.3%) of those receiving the general letter and 1.6% (CI 1.2–1.9%) of the control group. Effectiveness was limited to women whose test was no more than 10 years overdue, and was particularly strong for those whose test was 3–5 years overdue. Conclusions: This suggests that a reminder letter was effective, but that targeting the information in the letter did not further improve screening attendance. A second reminder letter sent to women before their Pap test is more than 5 years overdue has potential for increasing the number of women attending for screening.     

Comparative study of the ThinPrep Pap test and conventional cytology results in a Canadian cohort

OBJECTIVE: To compare the frequency of Pap test results in a prospective series of direct to vial ThinPrep tests to a cohort of conventionally prepared tests. To follow-up all test results for a minimum of 2 years and assess performance based on this outcome. METHODS: All women presenting for either routine screening or colposcopic examination in 2001 were enrolled in the ThinPrep cohort. A similar, population of conventionally prepared tests was extracted from the year 2000 laboratory data. Information on all concurrent and follow-up cervical specimens over the ensuing 2 years was retrieved. RESULTS: The ThinPrep cohort comprised 2288 Pap tests and the conventional, 2211. The frequency of normal [within normal limits (WNL) and benign cellular changes (BCC)] results in the ThinPrep cohort was 6% lower and the frequency of abnormal [> or =atypical squamous cells of undetermined significance (ASCUS)] results was 6.8% higher. Respective ThinPrep and conventional cohort results were 1156 (51%) and 1291 (58%) WNL, 625 (27%) and 561 (25%) BCC, 101 (4%) and 65 (3%) ASCUS, 21 (1%) and 2 (0.1%) atypical glandular cells of undetermined significance, 301 (13%) and 224 (10%) low-grade squamous intraepithelial lesion (LSIL), and 74 (3%) and 40 (2%) high-grade SIL (HSIL) (P < 0.0001). Follow-up was available for nearly 80% of each cohort. LSIL or higher was confirmed in 57.5% (n = 266) of the abnormal ThinPrep and 60.9% (n = 190) of the abnormal conventional tests. The ThinPrep yield of confirmed tests however was almost 50% higher than the conventional test. CONCLUSION: In this population, ThinPrep was superior to the conventional Pap test.     

Atypical glandular cells in cervical smears: histological correlation and a suggested plan of management based on age of the patient in a low-resource setting

Objectives:  To perform an audit of all smears reported as atypical glandular cells (AGC) using the Bethesda system (TBS) 2001.
Methods:  A total of 18 376 cervical smears were screened from January 2005 to June 2007, of which 65 cases were reported as AGC. Follow-up histology was available in 31 cases (47.7%), in whom a detailed cytological/histological correlation was carried out.
Results:  AGC constituted 0.35% of all Pap smears. Follow-up histology was normal or benign in 20 cases, whereas a squamous or glandular abnormality was seen in 11 cases. Squamous abnormalities included one case each of cervical intraepithelial neoplasia (CIN)1, CIN2 and CIN3 and five cases of squamous cell carcinoma. All glandular epithelial abnormalities were endometrial in origin and included two endometrial adenocarcinomas and one uterine serous carcinoma. Neither in situ nor invasive adenocarcinoma of the endocervix was observed. Review of smears and reclassification as AGC, not otherwise specified and favour neoplasia revealed a higher proportion of abnormality in the latter group, reaffirming the utility of subtyping. The median age of women with AGC was 41 years. The outcome was analysed with respect to the median age. In women aged equal or more than 40 years, AGC reflected a high-grade squamous or glandular epithelial abnormality in 50% of cases compared with none in those less than 40 years old ( P  = 0.010).
Conclusion:  The age of the woman as well as the subtype of atypical glandular cells influences outcome and hence must be taken into consideration while formulating an acceptable management strategy in these women in a low-resource setting.     

Effectiveness of a call/recall system in improving compliance with cervical cancer screening: a randomized controlled trial

OBJECTIVE: To determine the effectiveness of a simple call/recall system in improving compliance with cervical cancer screening among women not screened in the previous 3 years. DESIGN: Prospective randomized controlled study. SETTING: Two family medicine clinics (1 urban, 1 rural) affiliated with Memorial University of Newfoundland, St. John''s. PARTICIPANTS: A sample of women aged 18-69 years who were listed as patients of the clinics but who had not had a Papanicolaou test (Pap test) within the 3 years before the start of the study. Of 9071 women listed as patients 1360 (15.0%) had not undergone screening in the previous 3 years. A random sample of 650 were selected, 209 of whom were excluded because they had had a hysterectomy, had had a recent Pap test, had moved or had records containing clerical errors. This left 441 women for the study. INTERVENTION: The 221 women in the intervention group were sent a letter asking them to seek a Pap test and a reminder letter 4 weeks later. The 220 in the control group were sent no letters. MAIN OUTCOME MEASURES: Number of women who had a Pap test within 2 months and 6 months after the first letter was sent. RESULTS: Within 2 months, more women in the intervention group than in the control group had been screened (2.8% [5/178] and 1.9% (4/208] respectively). There was also a difference between the overall proportions at 6 months (10.7% [19/178] and 6.3% [13/208] respectively). None of the differences was statistically significant. CONCLUSION: A letter of invitation is not sufficient to encourage women who have never or have infrequently undergone a Pap test to come in for cervical cancer screening. The effectiveness of added recruitment methods such as opportunistic screening by physicians, follow-up by telephone and the offer of a specific appointment should be evaluated.     

CIN 2/3 and cervical cancer after an ASCUS pap smear. A 7-year, prospective study of the Norwegian population-based, coordinated screening program

OBJECTIVE: To estimate the risk of being diagnosed with cervical intraepithelial neoplasia (CIN) 2/3 or invasive cervical cancer (ICC) based on diagnostic and screening procedures performed after a diagnosis of atypical squamous cells of undetermined significance (ASCUS) and to compare this risk to that in women with a normal Pap smears. STUDY DESIGN: A 7-year, prospective, cohort study was performed in the Norwegian population-based, coordinated screening program. After excluding women in the midst of follow-up of an abnormal Pap smear or with a history of CIN 2/3 or ICC, the study population consisted of women 25-69 years of age with a normal (n = 526,661) or ASCUS Pap smear (n = 10,037) in 1995-1996. Risk estimates were calculated by logistic and parametric survival regression. RESULTS: Within 7 years of an ASCUS smear, 1,017 women (10.1%) were diagnosed with CIN 2/3 and 62 (0.62%) with ICC. Women with an ASCUS index Pap smear had a relative risk of 15-30 of being diagnosed with histologically verified CIN 2/3 or ICC within the first 2 years of follow-up as compared to women with a normal index smear. In long-term follow-up, women with an ASCUS index smear followed by a normal smear, which cancelled further clinical follow-up, were at > 3.5 times higher risk of both CIN 2/3 and invasive cancer as compared to women with a normal index smear. CONCLUSION: Pap smear follow-up of women with an ASCUS smear does not identify all women at higher risk of CIN 2/3 and ICC. Other diagnostic procedures should be implemented to improve the screening program.     

Value of combining HPV-DNA testing with follow-up Papanicolaou smear in patients with prior atypical squamous cells of undetermined significance

OBJECTIVE: To address human papillomavirus (HPV) testing on negative Pap tests preceded by atypical squamous cells of undetermined significance (ASC-US) without reflex HPV testing. STUDY DESIGN: Positive HPV test results with concurrent negative Pap tests over 1 year were identified. Pathology records for all patients diagnosed with ASCUS without reflex HPV testing in the previous year were reviewed; all cytologic and surgical specimens over the subsequent 2 years were evaluated for squamous abnormalities. RESULTS: Fifty patients had positive HPV DNA (HPV-DNA) test result combined with a negative Pap test. Twenty-three had a previous Pap test interpretation of ASC-US (without HPV testing) within the preceding year. On follow-up, 8 of 23 developed a squamous intraepithelial lesion (SIL) within 1 year. Four additional cases developed SIL in the second year after positive HPV testing. All dysplasias in the first year of follow-up were low grade; 1 of 4 developing in the second year was high grade. CONCLUSION: Negative Pap smear following an ASC-US interpretation without a concurrent HPV test is associated with significant false negative rate. We suggest consideration of combining HPV-DNA testing to all initial follow-up negative Pap tests of patients with previous ASC-US, if reflex HPV testing has not been performed.     

Pap smear screening in women under 30 in the Norwegian Coordinated Cervical Cancer Screening Program, with a comparison of immediate biopsy vs Pap smear triage of moderate dysplasia

OBJECTIVE: Top provide population based estimates of Pap smear screening results among women under 30 and to compare the outcomes of 2 triage options for women under 30 with a moderate dysplastic Pap smear: immediate biopsy vs. Pap smear follow-up. STUDY DESIGN: All Pap smears, histologically verified cervical intraepithelial lesion (CIN) 2/3 and invasive cervical cancer in 1999-2002 from women in Norway under 30 in 2000-2002 were analyzed. Due to different triage recommendations in different laboratories, 836 women under 30 with a moderately dysplastic Pap smear were recommended for immediate biopsy, while 109 were recommended for a Pap smear within 6 months. Risk estimates for triage outcome were estimated by multinominal logistic regression. RESULTS: The prevalence of squamous intraepithelial lesion was highest around 20 years. The first moderate dysplasia was diagnosed at age 16, as was CIN 2/3. Of the women with Pap smear triage, one third were diagnosed with a CIN 2+ lesion, one third had a normal outcome, while the last third were in uncertain state 12 months later. Among those recommended for immediate biopsy, nearly 70% were diagnosed with a CIN 2+, thus having odds of 4.2 (95% CI 2.5-7.1) higher than did women with Pap smear triage of being diagnosed with CIN2+ 12 months later. CONCLUSION: The choice of triage has a profound impact on the proportion of young women diagnosed with CIN 2+ after a moderately dysplastic Pap smear.     

Extrauterine malignancies. Role of Pap smears in diagnosis and management.

OBJECTIVE: To further elucidate the cytologic manifestations of extrauterine malignancies, to evaluate their possible distinction from primary cervical malignancies and to analyze their clinical significance and role in staging. STUDY DESIGN: Papanicolaou (Pap) smears in 33 cases with abnormal cells originating in histologically proven extrauterine carcinomas were evaluated. These cases came from the files of the Medical College of Pennsylvania and Lankenau Hospitals. RESULTS: Ovary, gastrointestinal tract and breast were the three most frequent primary sites, accounting for 28 of the 33 cases (85%). The histologic types encountered were adenocarcinoma, 29 cases (88%); mucoepidermoid carcinoma, 1 (3%); small cell carcinoma, 1 (3%); cloacogenic carcinoma and large cell lymphoma, 1 (3%). The following diagnoses were rendered at the time of initial evaluation: adenocarcinoma consistent with metastasis, 21 cases; carcinoma, primary versus metastatic, 2; adenocarcinoma, suspicious for endometrial primary, 2; suspicious for carcinoma, 1; and atypical glandular cells, 7. CONCLUSION: The yield for positive Pap smear diagnoses in extrauterine malignancies is best in patients with an established diagnosis of a primary neoplasm. The degree of tumor differentiation and extent of tumor involvement did not appear to correlate with diagnostic yield. There appeared to be no statistically significant association of tumor diathesis with primary versus metastatic carcinoma and presence or absence of documented local involvement of the endometrium, cervix or vagina. Therefore, while Pap smears can serve as a diagnostic tool in the evaluation of extrauterine malignancies, they are best utilized as an adjunct to tumor staging and patient management.     

Introduction of the Bethesda System to Mainland China with a Web-based tutorial

OBJECTIVE: To validate the use of a Web-based tutorial to introduce the Bethesda System (TBS) to Mainland Chinese laboratories. STUDY DESIGN: Digitized color images of the diagnostic features in 20 Pap smears were displayed on a Web page. Participants were asked to give each smear a diagnosis using the reporting nomenclature employed in their laboratory or one that was familiar to them. This was followed by teaching images of each smear accompanied by text in English and Chinese that highlighted important features for making a diagnosis using TBS. Participants then reviewed the 20 original Pap smears and rendered a diagnosis using TBS. RESULTS: Pathologists and cytotechnologists at 17 laboratories located in 10 cities completed the exercise. The average diagnostic accuracy for the 20 Pap smears before and after the tutorial was 76% and 88%, respectively. CONCLUSION: Web-based tutorials can be used for disseminating cytologic information to widely dispersed laboratories in China and help enhance the practice of cytology, currently an underutilized diagnostic technique. However, such difficulties as lack of Internet connections in the laboratory, outdated computers and a lack of interest in cytology need to be overcome to ensure success.     

A human papillomavirus testing system in women with abnormal Pap results: a comparison study with follow-up biopsies

OBJECTIVE: To evaluate the efficacy of INFORM HPV using the SurePath collection method in women whose Pap tests indicated abnormal results. STUDY DESIGN: Ninety-two women from the gynecology clinics at The University of Texas M.D. Anderson Cancer Center who had Pap tests and underwent follow-up biopsies were selected for the study. This included 51 women with atypical squamous cells of undetermined significance (ASCUS), 23 women with low-grade squamous intraepithelial lesion (LSIL), 15 women with high-grade squamous intraepithelial lesion (HSIL) and 3 women with negative Pap results. The INFORM HPV, an in situ hybridization assay, testing for oncogenic types of HPV was performed, and the results were compared with follow-up biopsies. RESULTS: The positive rate of the INFORM HPV increased with higher grades of cytology diagnoses. The sensitivity of the INFORM HPV testing for predicting high-grade cervical intraepithelial neoplasia (CIN 2/3) also increased with higher grades of cytology diagnoses. A negative predictive value (NPV) of 94.9% and a specificity of 80.4% for predicting CIN 2/3 were observed in the ASCUS group. CONCLUSION: Using SurePath Pap specimens, the INFORM HPV lacks sufficient sensitivity and NPV for predicting CIN 2/3 in women with ASCUS. Therefore, use of the test as a triage tool is limited.     

Endometrial carcinoma detected with SurePath liquid-based cervical cytology: comparison with conventional cytology

Introduction: Conventional Pap smears (CPS) have little impact on the detection of endometrial carcinoma. Although liquid‐based cytology (LBC) is replacing CPS in the UK, experience with identification of endometrial cancers with this technique is limited. Aim: To compare the accuracy of the SurePath LBC with that of CPS for detection of endometrial cancers. Methods: Our study group comprised SurePath LBC samples reported as atypical endometrial cells and endometrial adenocarcinoma (classified respectively as borderline, code 8 and ?glandular neoplasia, code 6 for the NHS Cervical Screening Programme statistics) in 2004–2005. CPS reported as atypical endometrial cells or adenocarcinoma in 1993–1998 comprised the control group. Histological follow‐up was obtained. Results: Endometrial abnormalities were reported in 95 (0.073%) of 130 352 LBC samples, comprising 75 (0.058%) atypical endometrial cells and 20 (0.015%) endometrial adenocarcinoma reports. Of 409 495 CPS, 117 (0.029%) were diagnosed as endometrial abnormalities, comprising 59 (0.014%) atypical endometrial cells and 58 (0.014%) endometrial adenocarcinoma reports. Thus, the endometrial adenocarcinoma reporting rate was similar in both groups, but that for atypical endometrial cells was higher with LBC (P < 0.001). The positive predictive value for endometrial cancer of endometrial adenocarcinoma and atypical endometrial cell reports in the LBC group was 73.3 and 18.8%, respectively, compared with 42.3 and 6.7% in the CPS group. The endometrial adenocarcinoma patients in CPS group were older (mean age 62.5 years versus 56.5 years) and most (22/25) were symptomatic, whereas most (13/17) patients in the LBC group were asymptomatic at the time of sampling (P < 0.001). Conclusion: SurePath LBC is at least as accurate a method for detecting endometrial cancer as CPS. SurePath LBC demonstrates enhanced identification of endometrial pathology in asymptomatic women in the cervical screening programme.     

Variables associated with squamous intraepithelial lesions among women with a cytologic diagnosis of atypical squamous cells of undetermined significance.

OBJECTIVE: To identify factors among women with atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis that are associated with either low grade squamous intraepithelial lesions (LSILs) or high grade squamous intraepithelial lesions (HSILs). STUDY DESIGN: From January 1992 to June 1995, 1,660 women with a diagnosis of ASCUS were followed until the next follow-up appointment after the ASCUS diagnosis. Logistic regression analysis with either LSIL or HSIL at follow-up examination as a dependent variable was done with the following independent variables: patient age, method of follow-up, follow-up time, type of health care coverage and household income. RESULTS: In multivariate analyses, there was a 2.7-fold increase in the odds of LSIL (OR = 2.7, 95% CI = 1.3-5.8) for young women (< or = 25 years), a 2-fold decrease in the odds of LSIL (OR = .5, 95% CI .3-.9) for long time to follow-up (> 18 weeks after ASCUS diagnosis) and an 7.8-fold increase in the odds of LSIL (OR = 7.8, 95% CI = 5.1-11.9) for follow-up by colposcopic biopsy. For the odds of HSIL, there was a 6.8-fold increase (95% CI = 3.2-14.5) for follow-up by colposcopic biopsy as compared to Pap smears and a 3-fold decrease in the odds of HSIL (OR = 3, 95% CI = .1-.7) for high-income women (> $34,857). CONCLUSION: Our findings suggest that among ASCUS patients, younger women and those with shorter follow-up time are more likely to be diagnosed with LSIL. Women with a high income showed a protective association for HSIL. Colposcopic biopsy identified more LSIL and HSIL as compared to repeat Pap smear.     

Utility of the in situ detection of HPV in Pap smears diagnosed as within normal limits.

OBJECTIVE: To determine the clinical significance in normal Pap smears of HPV detection as determined by Hybrid Capture (HC) and in situ hybridization analyses. STUDY DESIGN: We studied 135 consecutive Pap smears as well as 46 other smears from high-risk patients each initially diagnosed as within normal limits. RESULTS: The 135 "normal" Pap smears were rescreened, and 6 (4%) where found to be either ASCUS or SIL. In the remaining 129 cases, HPV DNA was detected in 0% and 9%, respectively, using in situ hybridization and HC I. Upon rescreening the high-risk patients, nine (20%) were reclassified as having SIL/ASCUS; each was in situ hybridization positive, and eight were HC positive; six (67%) of these women developed SIL on follow-up. In the 37 Pap smears in high-risk women still within normal limits after manual rescreening, HPV was detected in 2% by in situ hybridization and 46% by HC; 6% of the HC-positive women developed SIL on follow-up. CONCLUSION: In situ hybridization rarely detects HPV in Pap smears diagnosed as within normal limits after manual rescreening. In situ hybridization is very effective in detecting rare, atypical cells in Pap smears diagnosed as within normal limits and, in a high-risk population, is predictive of SIL on clinical follow-up.     

Endometrial scraping cytology in women with extragenital malignancies

OBJECTIVE: To clarify the usefulness of endometrial scraping smears in women with extragenital malignancies. STUDY DESIGN: A total of 4,335 endometrial scraping smears were obtained during the 5-year period 1995-1999 at the National Kyushu Cancer Center and were retrospectively analyzed regarding extragenital malignancies. RESULTS: There were 88 cases of extragenital malignancies. Extragenital malignant cells were detected in endometrial smears in 13 cases. The cases consisted of 4 gastric cancers, 4 breast cancers, 2 lung cancers, 1 rectal cancer, 1 gastrointestinal stromal tumor of the small intestine and 1 case of adenocarcinoma of unknown origin. The patients' average age was 52.5 years. The symptoms and signs included abnormal vaginal bleeding, abdominal and lumbar pain, lower limb edema, abdominal mass and neck lymph node swelling. Both ascites and peritoneal dissemination were found in 8 cases. Ten of the 13 cases were diagnosed as of extrauterine origin based on the characteristic cancer cell appearance, the absence of cellular detritus among the poorly differentiated adenocarcinomas and, above all, the morphologic difference between normal endometrial cells and cancer cells. CONCLUSION: Endometrial scraping smears are useful for detecting extragenital malignant cells that enter the uterine cavity.