Bone tumor radiograph review by pathologists prior to pathologic diagnosis: a receiver operator curve analysis of diagnostic utility

OBJECTIVE: To assess the performance of quick rescreening as an internal quality control for cervical smears previously screened as negative and to compare this method with clinically indicated rescreening of negative smears and with further 10% random rescreening. STUDY DESIGN: In a small-workload laboratory with many different types of indications for cytology, during a three-month period, all gynecologic cytology smears considered negative for significant findings (anything above atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance (AGUS) in the Bethesda System) or inadequate were quickly rescreened using a 10 x objective. RESULTS: Of the total 2,188 smears processed, 164 (7.5%) were excluded from rapid review because they were positive on routine screening, and 2,024 cases were subjected to rapid rescreening: 1,925 (95.1%) cases were considered negative and 99 (4.9%) positive for significant findings; 58 of the latter were confirmed and 41 not confirmed by the cytopathologist's detailed examination. The 58 confirmed cases were classified as: 43 ASCUS/AGUS, 14 of low grade squamous intraepithelial lesion and 1 of invasive cancer. No cases of high grade squamous intraepithelial lesion were detected. CONCLUSION: Considering that the routine screening and internal quality control of the laboratory had detected 117 positive cases, the additional 58 represent a definite increase in the efficiency of a small-workload laboratory. In such a clinical setting, no additional case of a high grade lesion was detected by rapid rescreening. The increase in cost and time was considered very reasonable, and the method was incorporated as quality control for the laboratory. Clinically indicated rescreening of negative smears and random 10% rescreening after random rescreening did not add significantly to quality assurance.     

Lower genital tract neoplasia in women with HIV infection

Women who are infected with human immunodeficiency virus (HIV) are at greater risk for the development of lower genital tract neoplasia than are HIV-negative women. Among HIV-positive women, those who are more severely immunosuppressed appear to be at higher risk for cervical intraepithelial neoplasia (CIN), also known as squamous intraepithelial lesions (SILs). Women who are HIV-positive also are more likely than HIV-negative women to have multifocal lower genital tract neoplasia. Cervical cancer is one of the most important acquired immune deficiency syndrome (AIDS)--related malignancies in women. Cancer and intraepithelial neoplasia of the lower genital tract can be persistent, progressive, recurrent, and difficult to treat in HIV-positive women. The most effective method for treating SILs has not been determined. Regular performance of Pap smears in HIV-positive women is of critical importance, as is careful examination of the entire lower genital tract. Also, women with high-grade intraepithelial or cervical cancer should be tested for HIV.     

Costs of conventional radical radiotherapy versus continuous hyperfractionated accelerated radiotherapy (CHART) in the treatment of patients with head and neck cancer or carcinoma of the bronchus. Medical Research Council CHART Steering Committee

We have compared the results of targeted manual rescreening of 1211 randomly selected smears with the results of PAPNET-assisted rescreening of 1613 cervical smears, containing at least 6.3% low-grade squamous intraepithelial lesion (SIL). PAPNET diagnosis and the targeted rescreening diagnosis were compared with the initial report, issued on the corresponding smear. Reproducibility scores for inadequacy, presence of endocervical and endometrial cells, specific infections and squamous cell abnormalities were determined. The reproducibility scores for the diagnosis of inadequate smears and specific infections were lower with the PAPNET-assisted rescreening. The detection of squamous cell abnormalities was excellent for both methods (> 0.95), with a higher detection rate for false-negative smears with the PAPNET testing system.     

Analysis of false-negative and underreported smears in the Florence district screening program for cervical carcinoma

AIMS AND BACKGROUND: To review false-negative or underreported (reactive changes, squamous or glandular atypia) smears performed in women developing histologically proven CIN2 or more severe lesions within 24 months and evaluate error causes. The study setting was the Florence District cervical cancer population-based screening: about 60,000 women age 25-60 years screened per year. METHODS: 118 false-negative or underreported cases were identified at screening files-cancer Registry matching, and the original smears were reviewed by six independent readers to judge smear adequacy and error type. RESULTS: Sampling errors (reported as inadequate, negative or less severe than CIN1 at review) accounted for 74% and screening/interpretation errors (reported as CIN1 or more severe at review) accounted for 26% of studied cases. Screening/interpretation errors were more likely ascribed to misinterpretation and underreporting than to misperception of cellular abnormalities. CONCLUSIONS: Quality control should above all address the problem of sampling adequacy. Due to the rarity of misperceived abnormalities (true screening errors), manual or automated rescreening of negative smears would not be an effective procedure for quality control.     

Use of the Thin Prep Pap Test in clinical practice

The Thin Prep Pap Test (Cytyc Corp., Boxborough, MA) received approval by the Food and Drug Administration in May 1996 as an alternative to the traditional conventional smear. The present direct-to-vial study assessed the utility of thin-layer technology for cervicovaginal screening in clinical practice. From May 1997-February 1998 (10 mo), 15,006 cervical smears were processed and evaluated; of these, 5,423 (36.1%) were conventional smears (CS) and 9,583 (63.9%) were Thin Prep slides (TP). Both methods were analyzed to compare specimen adequacy and detection rates of cervical lesions. The TP method reduced the "satisfactory but limited by" rate by 97% and the unsatisfactory rate by 63%. For low-grade squamous intraepithelial lesions (LSILs), TP slides yielded 3.6% (348/9,583) as compared to 0.98% (53/5,423) for CS, an increase of 267%. The TP method detected a threefold increase in the number of high-grade squamous intraepithelial lesions (HSILs) of 1.0% (100/9,583), as compared to 0.3% (17/5,425) for the CS group. The atypical squamous cells of undetermined significance/squamous intraepithelial lesion (ASCUS SIL) ratio was reduced by 54% in the TP group. In routine usage in our laboratory, the Thin Prep Pap Test yielded a significant increase in the detection of LSILs and HSILs as compared to conventional smears. Specimen adequacy was significantly improved.     

Does the menstrual cycle and use of oral contraceptives influence the risk of low back pain? A prospective study among female soccer players

BACKGROUND: There is an increasing number of articles regarding the long term follow-up of Papanicolaou (Pap) smears with the diagnosis of atypical squamous cells of undetermined significance (ASCUS). Much controversy exists regarding the management of patients with this diagnosis. In a prior study in 1992, the authors performed automated rescreening of 101 ASCUS cases and 91 negative (control) cases. They found that through PAPNET-directed rescreening, 35 of 101 ASCUS cases (35%) could be reclassified as a squamous intraepithelial lesion (SIL). METHODS: These 192 women were followed since 1992 through manual look backs of subsequent Pap smears and surgical biopsies over a 4-year period. The population studied was comprised of predominantly black women between the ages of 14 and 85 years. The majority were considered a high risk population because many had a history of several sexual partners and multiple pregnancies. RESULTS: Eighteen of 74 patients (24.3%) with an original diagnosis of ASCUS were found on subsequent Pap smears to have an SIL. Only 4 of 64 patients (6%) who originally had a negative Pap smear subsequently were found to have a low grade squamous intraepithelial lesion (LGSIL) within 4 years. Through ordinal logistic regression analysis, it was found that patients with an ASCUS diagnosis had a risk of developing SIL that was 2.6 times greater than the risk for patients with a negative smear diagnosis. Comparing the surgical biopsies in the control and ASCUS groups, there was no statistically significant difference in the risk of developing SIL. This may be because the number of follow-up biopsies were small. CONCLUSIONS: A statistically significant difference of the risk of developing SIL exists between patients with a negative smear versus those with an ASCUS smear. Long term follow-up is essential in the management of the patients with an ASCUS smear because there is clearly an increased risk of developing SIL.     

Improved cervical smear assessment using antibodies against proteins that regulate DNA replication

Carcinoma of the cervix is one of the most common malignancies. Papanicolaou (Pap) smear tests have reduced mortality by up to 70%. Nevertheless their interpretation is notoriously difficult with high false-negative rates and frequently fatal consequences. We have addressed this problem by using affinity-purified antibodies against human proteins that regulate DNA replication, namely Cdc6 and Mcm5. These antibodies were applied to sections and smears of normal and diseased uterine cervix by using immunoperoxidase or immunofluorescence to detect abnormal precursor malignant cells. Antibodies against Cdc6 and Mcm5 stain abnormal cells in cervical smears and sections with remarkably high specificity and sensitivity. Proliferation markers Ki-67 and proliferating cell nuclear antigen are much less effective. The majority of abnormal precursor malignant cells are stained in both low-grade and high-grade squamous intraepithelial lesions. Immunostaining of cervical smears can be combined with the conventional Pap stain so that all the morphological information from the conventional method is conserved. Thus antibodies against proteins that regulate DNA replication can reduce the high false-negative rate of the Pap smear test and may facilitate mass automated screening.     

Social support among African-American adults with diabetes. Part 1: Theoretical framework

BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) is a cytopathologic term used to describe cases without specific pathologic substratum. Between 10-60% of ASCUS cases correspond to squamous intraepithelial lesions (SIL). METHODS: The objectives of this study were: 1) to detect the pathologic significance of ASCUS in study patients, 2) to determine whether PAPNET identifies these cases, and 3) to compare the results of PAPNET with those of a second conventional screening. One hundred and sixty-three consecutive patients with the cytologic diagnosis of ASCUS and adequate follow-up were selected. Of these, 111 patients had colposcopic lesions and biopsies were performed; in the remaining 52 cases colposcopy was negative, as were 3 consecutive annual Papanicolaou smears. In a blind review, all 163 cases were rescreened using PAPNET. A second manual screening was performed for comparison. RESULTS: One hundred and twenty-six of the 163 cases (77.3%) showed no SIL on biopsy or follow-up. Of the 37 pathologic cases, the diagnosis was koilocytosis (flat condyloma) in 13 cases (8%), cervical intraepithelial neoplasia (CIN) type I in 11 cases (6.8%) low grade SIL [LSIL] in a total of 24 cases [14.8%]), and CIN II-III or high grade SIL (HSIL) in 11 cases (6.8%). In the review using PAPNET, 57 previous ASCUS cases were classified correctly as negative, and 7 of 13 koilocytosis cases (54%), 9 of 11 CIN I cases (82%), and 7 of 11 CIN II-III cases (64%) were diagnosed correctly. In the second conventional screening, 74 cases were negative and 77 cases were ASCUS; only 3 of 13 koilocytosis cases (23%), 4 of 11 CIN I cases (36.4%) and 5 of 11 CIN II-III cases (45.5%) were reclassified correctly. CONCLUSIONS: Among 163 patients with ASCUS, 77.3% had no precancerous squamous lesions. Concordance with definitive diagnosis was more accurate in our study using PAPNET analysis (Kappa index [K] = 0.7158) than by second conventional screening (K = 0.4537). Furthermore, we reclassified 35% of smears as negative and 15% as SIL.     

Rescreening in gynecologic cytology. Rescreening of 8096 previous cases for current low-grade and indeterminate-grade squamous intraepithelial lesion diagnoses--a College of American Pathologists Q-Probes study of 323 laboratories

OBJECTIVE: To quantitate, characterize, and analyze errors identified in the rescreening of previous gynecologic cytology specimens with original diagnoses of within normal limits or benign cellular changes for current cases diagnosed as low-grade squamous intraepithelial lesion or squamous intraepithelial lesion of indeterminate grade. DESIGN AND SETTING: College of American Pathologists Q-Probes laboratory quality improvement study in 323 laboratories. MAIN OUTCOME MEASURE: False-negative rate in cases rescreened as a result of a current cytologic diagnosis of low-grade squamous intraepithelial lesion or squamous intraepithelial lesion of indeterminate grade. RESULTS: A total of 8096 smears performed within the 5 years preceding the current examination were rescreened. Of the rescreened cases, 284 (3.5%) were reclassified as a squamous intraepithelial lesion or carcinoma, 474 (5.9%) as atypical squamous cells of uncertain significance, 7 (0.09%) as atypical glandular cells of uncertain significance or glandular intraepithelial lesion, and 39 (0.5%) as unsatisfactory. Ninety-three percent (261/280) of all false-negative cases were identified in cases from the previous 3 years. CONCLUSION: Rescreening archival cytology cases previously diagnosed as within normal limits or benign cellular changes for current cases diagnosed as low-grade squamous intraepithelial lesion or squamous intraepithelial lesion of indeterminate grade will identify screening and diagnostic errors. This may be a useful quality improvement monitor in many laboratories.     

2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity

OBJECTIVE: To evaluate the results of cervical cytology screening in the National Breast and Cervical Cancer Early Detection Program and to compare the findings with results from other screening programs. METHODS: We analyzed data on 312,858 women aged 18 years and older who received one or more Papanicolaou smears, and follow-up if indicated, from October 1991 through June 1995 at screening sites across the United States providing comprehensive National Breast and Cervical Cancer Early Detection Program services. RESULTS: Of the women screened, more than half were 40 years or older; slightly less than half (44%) were of racial and ethnic minorities. During the first screening cycle, 3.8% of Papanicolaou tests were reported as abnormal (squamous intraepithelial lesion [SIL] or squamous cell cancer); proportions of abnormals decreased with increasing age. The age-adjusted rate of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or worse among women screened was 7.4 per 1000 Papanicolaou tests; rates of CIN were highest among young women, but cancer rates peaked among women in their 50s and 60s. The percentages of first screening cycle-Papanicolaou tests interpreted as high-grade SIL and squamous cell carcinoma associated with biopsy-confirmed CIN II or worse (the positive predictive value) were 56.0% for CIN II/III and 3.7% for invasive cancer. Of the 150 invasive cancers diagnosed, 54.0% were classified as local disease. CONCLUSION: Observed results emphasize the duality of cervical neoplasia-CIN in younger women and invasive cancer in older women. This finding points to the importance of reaching both younger and older women for cervical cancer screening.     

The effect of route of delivery on regression of abnormal cervical cytologic findings in the postpartum period

OBJECTIVES: We sought to determine whether pregnant women with abnormal antepartum cervical cytologic findings differ in their postpartum rates of regression with respect to mode of delivery. STUDY DESIGN: Between 1990 and 1997, 446 pregnant women with antepartum abnormal cervical cytologic findings were identified. Complete demographic, clinical, and cytologic reports were available for 138 women. Papanicolaou smear data were collected and separated into three groups by use of the Bethesda classification system (atypical squamous cells of undetermined significance, low-grade squamous intraepithelial cells, and high-grade intraepithelial cells). Postpartum regression rates of antepartum Papanicolaou smears, with respect to degree of squamous epithelial cell abnormality and mode of delivery, were analyzed by Fisher's exact and Wilcoxon rank sum tests. RESULTS: Of the 138 women, 109 (79%) were delivered vaginally and 29 (21%) by cesarean section. No statistically significant difference was found between women delivered vaginally and those delivered by cesarean section with respect to age, parity, and smoking history within the three groups (atypical squamous cells of undetermined significance, low-grade squamous intraepithelial cells, and high-grade squamous intraepithelial cells). The overall postpartum regression rate for the 59 women with antepartum high-grade squamous intraepithelial cells was 48%. Of the 47 women with high-grade squamous intraepithelial cells who were delivered vaginally, 28 showed regression in the postpartum period versus none of the 12 women delivered by cesarean section (60% vs 0%, p < 0.0002). CONCLUSION: Postpartum spontaneous regression of Papanicolaou smears consistent with high-grade squamous intraepithelial cells occurs with increased frequency among women who are delivered vaginally versus by cesarean section.     

Comparing two modalities of management of women with cytologic evidence of squamous or glandular atypia: early repeat cytology or colposcopy

Early repeat cytology is recommended in most screening programs for cervical cancer in subjects with squamous or glandular abnormalities not amounting to neoplasia (atypical squamous cells of undetermined significance, ASCUS), but immediate colposcopy is also recommended in some countries, especially those where there is easy access to colposcopic facilities. We evaluated the cost-effectiveness of the two procedures in a prospective study of women with cytologic ASCUS, invited to cytocolposcopic assessment after 6 months. Colposcopy-directed biopsy was assumed as the gold standard, and the accuracy of colposcopy at 6 months was assumed to be equal to that of immediate colposcopy. Out of 874 compliers, punch biopsy was performed in 303 cases (34.7%), and 19 CIN2+ lesions were detected (CIN2 = 12, CIN3 = 6, microinvasive carcinoma = 1). Detecting 13 CIN2+ lesions at colposcopy required 874 colposcopies and 303 directed biopsies: the cost per CIN2+ lesion detected with the procedure was 2,749 US$. Detecting 15 CIN2+ lesions at repeat cytology required 874 cytologic examinations, 137 colposcopies, 64 directed biopsies, and 6 diagnostic large-loop resections, the latter being performed in subjects with high-grade squamous intraepithelial lesion and less severe lesions at punch biopsy: the cost per CIN2+ lesion detected with the procedure was 1,961 US$. The policy of repeat smear was more cost-effective than immediate colposcopy. According to such results, the protocol of the Florence screening program has been modified since October 1996.     

Radiotherapy of humero-scapular periarthritis using ultra-hard photons. Evaluation by MRI findings

OBJECTIVE: To determine the clinical implications of atypical glandular cells of uncertain significance (AGCUS) in cervical cytologic smears. STUDY DESIGN: Retrospective analysis. RESULTS: Eighty-eight of 32,181 (0.27%) cervical smears obtained during the study period contained AGCUS. Of the 47 women with AGCUS, 16 had intraepithelial or invasive neoplasms (34%; 95% confidence interval, 21-49%), including 9 low or high grade squamous intraepithelial lesions, 1 adenocarcinoma in situ of the cervix, 3 adenocarcinomas of the cervix, 2 adenocarcinomas of the endometrium and 1 adenoid basal cell carcinoma of the cervix. CONCLUSION: The high prevalence of cervical and endometrial neoplasia among women with the isolated finding of AGCUS on cervical cytologic smears warrants a thorough diagnostic evaluation.     

Lower moiety heminephroureterectomy in the duplex refluxing kidney: the accuracy of isotopic scintigraphy in functional assessment

OBJECTIVE: To estimate the incidence of dysplasia in patients with Papanicolaou smears showing atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (SIL) and to identify clinical predictors of dysplasia in these patients. METHODS: Patients referred for ASCUS and low-grade SIL were reviewed retrospectively. All patients were evaluated with immediate colposcopy. A multivariate logistic regression analysis was performed to identify clinical predictors of histologic SIL and histologic high-grade SIL. RESULTS: One hundred thirty-seven (34%) of 406 consecutive patients had histologic SIL. Regression analysis identified age (under 35 versus 35 years or above) and initial smear (low-grade SIL versus ASCUS) as statistically significant predictors of histologic SIL and high-grade SIL (P < .001). When patient outcomes were analyzed by age and initial Papanicolaou smear results, the subgroup of patients 35 years or older with ASCUS had low incidences of histologic SIL (14%) and high-grade SIL (1%). The other subgroups (under 35 years with ASCUS, under 35 years with low-grade SIL, and 35 years or older with low-grade SIL) had incidences of histologic SIL and histologic high-grade SIL of at least 28% and 14%, respectively. CONCLUSION: The high incidence of dysplasia in patients with minimally abnormal Papanicolaou smears suggests that immediate colposcopy might be appropriate for many of these patients. Age and initial Papanicolaou smear are predictive of dysplasia and might be used to select patients who have low incidence of dysplasia and might not require immediate colposcopy.     

Percentages of cervical cytologic diagnoses as a quality assurance method

OBJECTIVE: To demonstrate empirically that the efficiency of rescreening to discover false negative cytologic diagnoses is greatly enhanced by prospectively stratifying accessions according to risk level. STUDY DESIGN: We stratified accessions from 11 clinical sources and established the rate of diagnoses according to three categories: (1) "within normal limits"/"benign cellular changes" (WNL/BCC), (2) "atypical squamous/glandular cells of undetermined significance" (ASCUS/AGCUS) and (3) "squamous intraepithelial lesion/invasive carcinoma" (SIL/CA). We then prospectively rescreened all negative smears from sources with rates of positive diagnoses (ASCUS/AGCUS and SIL/CA) in excess of 20% and 5% of negative smears from sources with rates of positive diagnoses < 20%. We compared the detection rates of false negatives on rescreening target groups with random rescreening of 10% of all negative smears. RESULTS: The rates of SIL/CA, ASCUS/AGCUS and WNL/BCC varied from 0 to 43%, 4% to 14% and 46% to 94%, respectively. Rescreening 10% of all negative smears revealed a false negative fraction of 3%; rescreening target groups revealed a false negative fraction of 5.9%. CONCLUSION: The yield of prospectively detected false negative diagnoses was significantly increased by targeting high-risk accession groups. When cytology laboratories serve diverse populations, stratifying accessions by risk to permit increased sampling from the proportionately higher risk categories is a simple and effective device to maximize the yield and benefit from rescreening.     

Evolution of atypical gynecological cervical smears in a captive population

BACKGROUND: An atypical cervical smear may represent a wide variety of lesions, from banal diseases to invasive neoplastic lesions. AIM: To study the evolution of atypical cervical smears in a highly controlled women population. MATERIAL AND METHODS: A retrospective analysis of 117 women with atypical cervical smears, diagnosed between 1985 and 1994, was performed at the institutional hospital of a mining corporation in Chile. RESULTS: Patients age ranged from 25 to 65 years. Six percent of atypical cervical smears were associated to Papillomavirus infection and 25% to unspecific infectious agents. In the second smear, during follow up, 22.2% of women had some degree of squamous intraepithelial lesion or signs of Papillomavirus infection. A cervical biopsy was performed to 69 women, confirming the presence of a squamous intraepithelial neoplasia or signs of Papillomavirus infection in 38.4% of them. Only one patient had microinvasion. CONCLUSIONS: All patients with atypical gynecological cervical smears should be closely followed to ascertain the diagnosis.     

The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice

OBJECTIVE: To evaluate the effectiveness of the AutoPap System in detecting abnormal and normal cervical smears when used in a primary screening/quality control mode, as compared with currently established laboratory practices. STUDY DESIGN: Slides were obtained prospectively and were initially processed in the routine fashion with cytotechnologist screening followed by 10% random quality control rescreening. Slides were then processed on the AutoPap System and allocated into the following groups: (1) approximately 25% of the lowest-ranking slides were placed in the laboratory's archives as within normal limits; (2) the remaining approximately 75% of slides were subjected to manual screening. Approximately 15% of the highest-ranking slides in this group underwent quality control rescreening. For each slide needing manual screening, the cytotechnologist was supplied with a report giving the ranking score of that slide. All discrepant slides for either adequacy or diagnosis were subjected to a truth-determination process. The results obtained from the two arms of the protocol were then compared. RESULTS: The AutoPap System-assisted arm of the study was superior to the current practice arm for the identification of abnormal slides at the level of atypical squamous cells of undetermined significance and above (ASCUS+), low grade squamous intraepithelial lesion (LSIL) and higher LSIL+. AutoPap System-assisted practice was equivalent to current practice for the identification of unsatisfactory and satisfactory but limited by slides. All results showed statistical significance. In addition, AutoPap System-assisted practice in the study indicated improved specificity of diagnosis. CONCLUSION: AutoPap System-assisted practice shows superior sensitivity and specificity when compared to current practice. Its clinical use as a primary screening device should improve the overall practice of cervical cytology as well as provide potential enhancement in overall laboratory productivity.     

Squamous intraepithelial lesions of the cervix, invasive cervical carcinoma, and immunosuppression induced by human immunodeficiency virus in Africa. Dyscer-CI Group

BACKGROUND: Squamous intraepithelial lesions (SILs) of the cervix are associated with human immunodeficiency virus (HIV) infection, but multiple risk factors must be considered in this context. The authors performed a cross-sectional study to assess the prevalence of and the factors associated with SILs and invasive cervical carcinoma (ICC). METHODS: In Abidjan, C?te d'Ivoire, women were recruited from three outpatient gynecology clinics and screened for both cervical disease and HIV infection. A CD4 cell count was performed for HIV-infected women. RESULTS: A total of 2198 women were included in the study. The prevalence of HIV infection was 21.7%. Of the 2170 women who underwent a cervical screening, 254 (11.7%) presented with a dysplasia or neoplasia: 7.6% had low grade SILs (LSILs), 3.3% had high grade SILs (HSILs), and 0.8% had ICCs. In multivariate analyses, factors associated with these lesions were as follows: for LSILs, HIV-1 seropositivity, age <24 years, parity >1, consultation for genital infection, and no use of oral contraception in the past; for HSILs, HIV-1 seropositivity, chewing tobacco use, low educational level, and parity >1; and for ICCs, age >33 years, parity >3, and illiteracy. In women infected with HIV-1, the prevalence of LSILs increased with a decrease in CD4 cell count, whereas this relation was not found among patients with HSILs. ICCs were linked to HIV-2 infection, but not to HIV-1 infection, in univariate analysis. CONCLUSIONS: In Africa, the prevalence of SILs is high. The factors associated with precancerous and cancerous lesions are different. Cancers in women infected with HIV-1 often may not reach the invasive stage. These findings could have implications for cervical screening programs in the future.     

Detecting structural changes at the molecular level with Fourier transform infrared spectroscopy. A potential tool for prescreening preinvasive lesions of the cervix

OBJECTIVE: To study cervical exfoliated cells with Fourier transform infrared spectroscopy (FTIR). STUDY DESIGN: Consecutive samples from 133 women attending the Dysplasia Clinic, Ottawa Civic Hospital, were collected in balanced electrolyte solution. After centrifugation, two smears were prepared for routine screening. The remainder of the pellet was frozen for FTIR spectroscopic study. RESULTS: In 120 samples, adequate material was available for spectroscopic study. All smears from 17 women with normal spectra were within normal limits (WNL). One hundred three spectra were abnormal. The corresponding smears were interpreted as: 41 low grade squamous intraepithelial lesions, 20 high grade squamous intraepithelial lesions, 6 atypical squamous cells of undetermined significance, 17 cases with benign cellular changes, and 19 WNL. Ten of 17 cases with benign cellular changes had characteristic spectra consistent with inflammatory changes. CONCLUSION: FTIR spectroscopy is a highly sensitive technique for detecting cervical abnormalities and a potential tool for prescreening preinvasive lesions of the cervix.     

Psychological stress in the workplace and menstrual function

Invasive squamous carcinoma of the uterine cervix (CC) arises from sequential progression of low-grade (L) and high-grade (H) squamous intraepithelial lesions (SILs). In clinical observations, these lesions are frequently found as synchronous multiple foci. The nature and evolutionary mechanism of these lesions are largely unknown. We have performed allelotyping of three 3p markers (at 3p14, 3p22-24, and 3p25) on 22 LSILs and 15 HSILs microdissected from patients with multiple (n = 21) or uniform (n = 6) cervical lesions. The results were analyzed together with our previous allelotyping of 57 deeply invasive CCs. Loss of heterozygosity at one of the three markers was observed in 23%, 27%, and 31 % of LSILs, HSILs, and CCs, respectively. Frequent and early allelic loss was noted (in 30% of LSILs and 50% of HSILs) at 3p14, which may harbor tumor suppressor genes involved in early stages of cervical carcinogenesis. A high frequency of microsatellite alteration (MA) was found in LSIL (41%) and HSIL (67%) but not in CC (5.3%). In particular, MA was more frequently found in low-grade lesions in association with invasive cancers (75%, 6/8) than in those associated with SILs (29%, 4/14) (P < 0.05). Together with the finding of a monoclonal origin of premalignant and malignant cervical lesions, the present results allow us to propose a model of local field effect of genomic instability that progressively affects the clonal evolution of SIL of uterine cervix.