Diagnosis Of Squamous Intraepithelial Lesions Research Articles

ThinPrep Pap Test: performance and biopsy follow-up in a university hospital.

The ThinPrep Pap Test (TP), a liquid-based cervical cytology preparation, was approved for use in the U.S. in 1996. The purpose of this study was to compare TP performance and biopsy follow-up studies with a similar population of high risk patients sampled by conventional Papanicolaou (Pap) smear (CS). Diagnostic and specimen adequacy interpretations for 2727 TP direct-to-vial Pap tests from a high risk university hospital practice were compared with 5000 CS preparations from the same physicians taken 1 year previously. Biopsy follow-up studies for the categories of squamous intraepithelial lesion (SIL), carcinoma, and atypical squamous cells of undetermined significance (ASCUS) for each time period and technique were contrasted. The SIL/carcinoma detection rate increased from 7.7% to 10.5% (P < 0.01) and the ASCUS rate decreased from 12.5% to 6.9% (P < 0.01); the percentage of satisfactory but limited specimens decreased from 19.4% to 10.5% (P < 0.01). Low grade SIL cases increased by 57% (P < 0.01) whereas the 26% increase in high grade SIL cases was not statistically significant. Greater than 90% of ungraded SIL, high grade SIL, and carcinoma cases had abnormal biopsies by both the TP and CS methods. The number of biopsy-confirmed high grade dysplasias and carcinomas was similar in the two groups. A low grade SIL detected by TP was less likely to have an abnormal biopsy (70% vs. 85% for CS). Nevertheless, the 57% increase in low grade SIL diagnoses by TP resulted in more TP patients with dysplastic biopsy diagnoses. Follow-up studies for ASCUS cases diagnosed by either TP or CS were similar, and 21-24% of patients eventually were found to have dysplasia. The TP technique appears to lead to the increased detection of low grade SIL lesions, decreased satisfactory but limited samples, and fewer equivocal specimens. No increase in biopsy-confirmed high grade dysplasias and carcinomas was found. Follow-up studies for the ASCUS category were nearly identical to those for CS.

Short-term follow up of cervical squamous intraepithelial lesions associated with HIV and human papillomavirus infections in Africa.

A prospective study in gynaecology clinics was conducted in Abidjan, Côte d'Ivoire, to assess the short-term evolution of squamous intraepithelial lesions (SILs). Of 94 women with a cytological diagnosis of SIL, 38 were infected with HIV. The average follow-up period after the initial smear was 5 months. Detection of human papillomavirus (HPV) by polymerase chain reaction (PCR) was performed at both the time of enrolment and final follow-up smear. There were 39 cases of persistent SILs. HIV-positive women had a higher percentage of persistent SIL (76%) than HIV-negative women (18%, relative risk (RR)=4.3, 95% confidence interval (CI) = 2.4, 7.7). SILs were more frequent among women infected with HPV at the time of enrolment or with persistent HPV infection, but these associations disappeared after adjusting for HIV serostatus. Spontaneous regression of SILs commonly occurs in HIV-negative African women. HIV-infected women with cervical dyskaryosis require gynaecology follow-up.

Short-term follow up of cervical squamous intraepithelial lesions associated with HIV and human papillomavirus infections in Africa

A prospective study in gynaecology clinics was conducted in Abidjan, Côte d'Ivoire, to assess the short-term evolution of squamous intraepithelial lesions (SILs). Of 94 women with a cytological diagnosis of SIL, 38 were infected with HIV. The average follow-up period after the initial smear was 5 months. Detection of human papillomavirus (HPV) by polymerase chain reaction (PCR) was performed at both the time of enrolment and final follow-up smear. There were 39 cases of persistent SILs. HIV-positive women had a higher percentage of persistent SIL (76%) than HIV-negative women (18%, relative risk (RR)=4.3, 95% confidence interval (CI)=2.4, 7.7). SILs were more frequent among women infected with HPV at the time of enrolment or with persistent HPV infection, but these associations disappeared after adjusting for HIV serostatus. Spontaneous regression of SILs commonly occurs in HIV-negative African women. HIV-infected women with cervical dyskaryosis require gynaecology follow-up.

Cost-Effectiveness Analysis of Diagnosis and Management of Cervical Squamous Intraepithelial Lesions

Objective: To compare five strategies for the diagnosis and treatment of cervical squamous intraepithelial lesions (SILs), including those that incorporate colposcopy and a new technology, fluorescence spectroscopy. Methods: On the basis of a health care perspective, we performed a cost-effectiveness analysis using a decision-analytic model for the diagnosis and management of SILs. We compared the five strategies based on the expected costs and number of cases that were treated appropriately, missed, treated inappropriately, and appropriately not treated in a hypothetical cohort of 100 patients referred after an abnormal Papanicolaou smear. Data on prevalence and operating characteristics were derived from the medical literature. Costs were adjusted from hospital charge data. Results: A see-and-treat strategy based on fluorescence spectroscopy was the least expensive but least effective strategy, costing $160,479 to detect 31.55 cases of cervical precancer accurately in 100 patients. The most expensive strategy was colposcopically directed biopsy, at $311,808 to find 45.78 cases; however, when both tests were used in a see-and-treat modality, slightly more cases were found (46.05) at a lower cost ($285,133). Other strategies were dominated in the base case. The incremental cost-effectiveness of the joint strategy compared with the spectroscopy-only strategy was $8596 per case of cervical precancer detected. Sensitivity analysis showed that the analysis was sensitive to the cost of the new technology of fluorescence spectroscopy. Conclusion: Fluorescence spectroscopy should be considered an important innovation in the diagnosis of SILs as demonstrated by its efficacy and economic advantages.

The AutoCyte Preparation System for Gynecologic Cytology

To determine if thin-layer processing of cervicovaginal samples improves detection of cytologic abnormalities by reducing problems related to direct smear preparation. Eight hundred fifty-two cervical samples were collected as part of a multicenter trial of the CytoRich/AutoCyte system. The Cervex Brush was used for specimen collection. Following preparation of a conventional Papanicolaou smear, the brush was placed in a vial of fixative. A thinlayer CytoRich preparation was prepared by sedimentation following centrifugation through a density gradient and then stained by the AutoCyte Preparation System according to the manufacturer's guidelines. The two preparations were masked and screened, and a diagnosis was rendered. Abnormal results from were reviewed by a pathologist. The specimens were later unmasked and the diagnoses compared. CytoRich and conventional cervical cytologic smears detected an equivalent number of squamous intraepithelial lesions (SILs) (27 vs. 29) and atypical squamous cells of undetermined significance (ASCUS) (19 vs. 21). Both methods missed an equivalent number of SILs (four vs. five). CytoRich detected more infections (151 vs. 115) and had 66% fewer nonspecific inflammatory diagnoses. CytoRich also had fewer "limited" adequacy evaluations (211 vs. 236). CytoRich preps improve adequacy; increase detection of infections, such as candidiasis and trichomoniasis; and are accurate in the diagnosis of SILs. CytoRich appears to be an equivalent and possibly better preparation for cervicovaginal cytology.

Appropriate follow-up interval for biopsy confirmation of squamous intraepithelial lesions diagnosed by cervical smear cytology.

Correlation of gynecologic cytology and histology is a routine component of quality assurance in all cytology laboratories. However, the appropriate interval for histologic follow-up has not been studied. We analyzed all cases with a cytologic diagnosis of squamous intraepithelial lesion (SIL) during a 1-year period that had histologic follow-up within 1 year of cytologic sampling. Six hundred ninety-six Papanicolaou smears with 811 corresponding biopsy specimens were identified. Of the cytologic diagnoses of SIL, 68% were confirmed by biopsy. Biopsy specimens were obtained most often at two times, one at the time of cytologic diagnosis and another 40 days later. The ratio of biopsy specimens with a diagnosis of SIL to those without was highest during the first 60 days. Approximately 1% of diagnoses took almost 1 year to be confirmed. A follow-up interval of 100 days detected 78% of all SIL diagnoses yet still permitted time to affect subsequent patient treatment in most cases if desired. We conclude that for clinical purposes, the interval for histologic follow-up of a cytologic diagnosis of SIL should be less than 60 days, but for quality assurance purposes, the interval should be approximately 100 days.

Reactive cellular change: is there an increased risk for squamous intraepithelial lesions?

The aim of this study was to evaluate the rate of squamous intraepithelial lesions (SIL) in women with reactive cellular change (RCC) cervical smears and compare the results with a control group with within normal limit (WNL) smears. The study group was comprised of 1000 women with RCC and a control group of 1000 women with WNL cervical smears diagnosed over an 8-month period. Results of the first follow-up (FU) smears were evaluated and compared between the two groups. FU smears with a diagnosis of SIL were reviewed along with the original RCC or WNL smears. Six hundred and thirteen women from the RCC group and 640 from the WNL group had FU smears. The mean time to FU was 11.0 and 13.8 months, respectively. FU revealed SIL in 24 of 613 smears in the RCC group (20 low grade [L] SIL and 4 high grade [H] SIL), (3.9%) and in 10 of 640 smears in the WNL group (10 LSIL and 0 HSIL) (1.6%). Fisher's exact test (two-tailed) showed statistical significance (P = 0.014). On retrospective review of the FU smears diagnosed as SIL and their corresponding original RCC or WNL smears, four RCC smears were upgraded to atypical squamous cells of undetermined significance (ASCUS). The remaining diagnoses remained unchanged. Women with RCC are more likely to have SIL on a FU smear compared with women with WNL smears (3.9% vs. 1.6%). It is important to emphasize that in the authors' laboratory, the rate of SIL in women with ASCUS is much higher (24%). Awareness of these rates combined with the clinical history may help clinicians determine whether women with RCC require closer FU.

Clinicopathologic correlation of the unsatisfactory papanicolaou smear

BACKGROUND The 1991 Bethesda System for cervical/vaginal cytology reporting defined adequacy criteria for the unsatisfactory designation. Most laboratories have implemented these criteria, but clinical implications have not been established. METHODS Researchers at two university hospitals retrieved by computer search all unsatisfactory Papanicolaou (Pap) smears taken between January 1994 and July 1995. Of 71,872 total Pap smears, 208 (0.3%) were unsatisfactory (corresponding atypical rate of 9% and a dysplasia/carcinoma rate of 6.5%). Time interval to follow-up and clinicopathologic outcome were determined. RESULTS Approximately 26% of unsatisfactory Pap smears were from patients with a history of epithelial abnormalities. The majority (129 of 208 specimens; 62%) of follow-up Pap smears or biopsies occurred within 6 months, 5.7% within 6-12 months, and 1.4% in 12-18 months. Approximately 31% had no follow-up. The first repeat Pap smear or histologic specimen in 144 patients with follow-up was negative in 107 (74%), unsatisfactory in 6 (4%), atypical squamous cells of undetermined significance in 15 (10%), squamous intraepithelial lesion (SIL) in 13 (9%), and malignant in 3 (2%). Nonmalignant conditions contributing to the unsatisfactory smears on histologic specimens (12%) included cervicitis, endometritis, endometrial hyperplasia, and polyps. Progressive abnormalities after the first repeat specimen were noted in 7 patients (5%). A total of 23 of 144 initial unsatisfactory specimens (16% )were found to be from patients diagnosed with SIL or malignancy when all follow-up specimens were analyzed. CONCLUSIONS The majority of patients with unsatisfactory Pap smears had follow-up studies within 6 months. A significant number (16%) of those with follow-up had eventual diagnoses of SIL or neoplasia. Benign pathologic conditions also contributed to unsatisfactory smears. This patient subset was more likely to have a history of abnormalities, confirming the importance of peer/hierarchical review of unsatisfactory smears. [See editorial counterpoint on pages 137-8, this issue.] Cancer (Cancer Cytopathol) 1997; 81:139-43. © 1997 American Cancer Society.

Clinicopathologic correlation of the unsatisfactory papanicolaou smear

The 1991 Bethesda System for cervical/vaginal cytology reporting defined adequacy criteria for the unsatisfactory designation. Most laboratories have implemented these criteria, but clinical implications have not been established. Researchers at two university hospitals retrieved by computer search all unsatisfactory Papanicolaou (Pap) smears taken between January 1994 and July 1995. Of 71,872 total Pap smears, 208 (0.3%) were unsatisfactory (corresponding atypical rate of 9% and a dysplasia/carcinoma rate of 6.5%). Time interval to follow-up and clinicopathologic outcome were determined. Approximately 26% of unsatisfactory Pap smears were from patients with a history of epithelial abnormalities. The majority (129 of 208 specimens; 62%) of follow-up Pap smears or biopsies occurred within 6 months, 5.7% within 6-12 months, and 1.4% in 12-18 months. Approximately 31% had no follow-up. The first repeat Pap smear or histologic specimen in 144 patients with follow-up was negative in 107 (74%), unsatisfactory in 6 (4%), atypical squamous cells of undetermined significance in 15 (10%), squamous intraepithelial lesion (SIL) in 13 (9%), and malignant in 3 (2%). Nonmalignant conditions contributing to the unsatisfactory smears on histologic specimens (12%) included cervicitis, endometritis, endometrial hyperplasia, and polyps. Progressive abnormalities after the first repeat specimen were noted in 7 patients (5%). A total of 23 of 144 initial unsatisfactory specimens (16% )were found to be from patients diagnosed with SIL or malignancy when all follow-up specimens were analyzed. The majority of patients with unsatisfactory Pap smears had follow-up studies within 6 months. A significant number (16%) of those with follow-up had eventual diagnoses of SIL or neoplasia. Benign pathologic conditions also contributed to unsatisfactory smears. This patient subset was more likely to have a history of abnormalities, confirming the importance of peer/hierarchical review of unsatisfactory smears.

Human Papillomavirus DNA Detection in Cervical Specimens by Hybrid Capture: Correlation with Cytologic and Histologic Diagnoses of Squamous Intraepithelial Lesion of the Cervix

Human Papillomavirus DNA Detection in Cervical Specimens by Hybrid Capture: Correlation with Cytologic and Histologic Diagnoses of Squamous Intraepithelial Lesion of the Cervix

Quantitative image analysis of MIB-1 reactivity in inflammatory, hyperplastic, and neoplastic endocervical lesions.

The diagnosis of endocervical neoplasia can be difficult as it is sometimes mimicked by proliferative or reactive glands. MIB-1 is a proliferation marker that can aid in the diagnosis of squamous intraepithelial lesions (SIL) of the cervix and vulva, but its potential value in the diagnosis of endocervical lesions has not been fully explored. Ten formalin-fixed, paraffin-embedded cases of each of the following were obtained: morphologically normal endocervical glands from patients with cervical SIL, endocervicitis, microglandular hyperplasia (MGH), and endocervical adenocarcinomas (eight in situ, two invasive). Microwave unmasking of antigens was performed prior to immunohistochemical staining for MIB-1 using the avidin/biotin peroxidase method. Labeling indexes were calculated for 34 specimens (10 adenocarcinoma. 8 each of the other diagnoses) using image analysis (Samba 4000). There was diffuse MIB-1 reactivity in adenocarcinoma (labeling index 57-96%, mean 80%), minimal focal reactivity in normal glands underlying SIL (labeling index 0.8-4.3%, mean 2.4%), moderate spotty reactivity in MGH (labeling index 2.9-18.4%, mean 8.5%), and minimal to focally diffuse reactivity in endocervicitis (labeling index 1.0-13.3%, mean 5.7%). These data indicate that the percentage and distribution of MIB-1-reactive endocervical cells can be of diagnostic utility in distinguishing neoplastic glands from those of endocervicitis and MGH.

Anal and cervical abnormality in women—prediction by human papillomavirus tests

A total of 151 women at risk of human immunodeficiency virus infection were investigated, to study the strength of the association between cervix and anus regarding the presence of HPV and cytological abnormality. An equal percentage of women had abnormal cervical (12.2%) and anal (12.1%) Papanicolaou smears. HPV measured by PCR was detected in 93.3% of cervical squamous intraepithelial lesions (SIL) compared to 49.1% of normal cervical cytologies, and in 100% of anal SIL and 67.4% of normal anal cytologies, respectively. After controlling for HPV-PCR status, immunodeficiency, as measured by a low CD4+ count and HIV positivity, increased the detection of cervical and to some extent anal squamous intraepithelial lesions (SIL). We evaluated how precisely an HPV test could predict cervical disease and found that the HPV-PCR test was slightly more sensitive than the HPV-hybrid capture (HC) test (PCR: 93.3% vs. HC: 88.9%), whereas the HC test was significantly more specific (83.6% vs. 50.9%), and with a much higher positive predictive value (43.2% vs. 20.6%). Similar results were obtained for anal SIL. HIV positivity increased sensitivity, lowered specificity and increased the positive predictive value of the tests. A diagnosis of cervical SIL was associated with a more than 3-fold increased risk of a simultaneous abnormal anal smear (p <: 0.05). In conclusion, cervical and anal disease were significantly associated and almost exclusively seen in the presence of HPV. Immunodeficiency and HIV positivity increased the risk of disease in HPV-positive subjects. Hybrid capture, which requires a higher viral load than PCR to detect HPV, was clearly superior in predicting cervical and anal disease. Altogether, these findings suggest that a high level of HPV infection may be important for the development of SIL in the population studied. © 1996 Wiley-Liss, Inc.

Anal and cervical abnormality in women--prediction by human papillomavirus tests.

A total of 151 women at risk of human immunodeficiency virus infection were investigated, to study the strength of the association between cervix and anus regarding the presence of HPV and cytological abnormality. An equal percentage of women had abnormal cervical (12.2%) and anal (12.1%) Papanicolaou smears. HPV measured by PCR was detected in 93.3% of cervical squamous intraepithelial lesions (SIL) compared to 49.1% of normal cervical cytologies, and in 100% of anal SIL and 67.4% of normal anal cytologies, respectively. After controlling for HPV-PCR status, immunodeficiency, as measured by a low CD4+ count and HIV positivity, increased the detection of cervical and to some extent anal squamous intraepithelial lesions (SIL). We evaluated how precisely an HPV test could predict cervical disease and found that the HPV-PCR test was slightly more sensitive than the HPV-hybrid capture (HC) test (PCR: 93.3% vs. HC: 88.9%), whereas the HC test was significantly more specific (83.6% vs. 50.9%), and with a much higher positive predictive value (43.2% vs. 20.6%). Similar results were obtained for anal SIL. HIV positivity increased sensitivity, lowered specificity and increased the positive predictive value of the tests. A diagnosis of cervical SIL was associated with a more than 3-fold increased risk of a simultaneous abnormal anal smear (p < 0.05). In conclusion, cervical and anal disease were significantly associated and almost exclusively seen in the presence of HPV. Immunodeficiency and HIV positivity increased the risk of disease in HPV-positive subjects. Hybrid capture, which requires a higher viral load than PCR to detect HPV, was clearly superior in predicting cervical and anal disease. Altogether, these findings suggest that a high level of HPV infection may be important for the development of SIL in the population studied.

Human Papillomavirus DNA Detection in Cervical Specimens by Hybrid Capture: Correlation with Cytologic and Histologic Diagnoses of Squamous Intraepithelial Lesions of the Cervix

Human papillomavirus (HPV) DNA detection in cervical specimens was correlated with cytologic and histologic diagnoses for 151 women who were referred to the Johns Hopkins Hospital colposcopy clinic for evaluation of an abnormal Pap smear. HPVs were identified as “high-risk” or “low-risk” by Hybrid Capture. The final disease status was categorized as high-grade squamous intraepithelial lesion (HSIL) by histology (n= 26), low-grade squamous intraepithelial lesion (LSIL) by histology (n= 43), equivocal [histology negative, cytology atypical squamous cells of undetermined significance (ASCUS) or higher,n= 42], and negative (both histology and cytology negative,n= 40). Thirty-five percent of disease-negative women and 84% of the women with biopsy-proven or equivocal disease were HPV-positive. Ninety-two percent of the HPV-positive women harbored high-risk HPVs, either high-risk HPVs alone (77%) or high-risk HPVs along with low-risk HPVs (15%). High-risk HPVs predominated in disease-negative as well as disease-positive women. Collection of specimens with a cytobrush was more efficient for HPV DNA detection than collection by cervicovaginal lavage. Large amounts of HPV DNA correlated with presence of HSIL or LSIL. For detection of HSIL, considering only brush samples, the sensitivities of abnormal cytology (ASCUS or higher), of high-risk HPVs, and of the two combined were, respectively, 87, 93, and 100%; the corresponding specificities were 30, 30, and 20%. HPV DNA detection may be most beneficial in populations with low HPV prevalence.

Diagnostic performance of Hybrid Capture human papillomavirus deoxyribonucleic acid assay combined with liquid-based cytologic study

OBJECTIVE: Our purpose was to determine the diagnostic performance of human papillomavirus deoxyribonucleic acid testing when performed on liquid-based (Thin-prep) cytologic samples. STUDY DESIGN: Thin-prep cytologic study, human papillomavirus deoxyribonucleic acid assay with probes for high oncogenic risk human papillomavirus types (16, 18, 31, 33, 35, 45, 51, 52, and 56), and cervical biopsies on women referred to colposcopy for an abnormal Papanicolaou smear were performed. RESULTS: Of the 364 patients, 186 (51.6%) had a low-grade squamous intraepithelial lesion or worse by histologic diagnosis. Human papillomavirus deoxyribonucleic acid quantitation was correlated with a histologic diagnosis of squamous intraepithelial lesion (p < 0.0001) and the morphologic severity (p < 0.01). The combination of Thin-prep cytologic study and human papillomavirus deoxyribonucleic acid testing correctly identified 87.7% of histologic low-grade lesions and 95.1% of the women with high grade lesions and invasive cancer (p < 0.01). CONCLUSIONS: A liquid-based cytologic system provides adequate material for concomitant human papillomavirus testing. Addition of human papillomavirus testing to Thin-prep cytologic study provides significant gains in diagnostic accuracy over either cytologic study or human papillomavirus deoxyribonucleic acid testing alone. (Am J Obstet Gynecol 1996;175:651-6.)

PAPNET-directed rescreening of cervicovaginal smears: a study of 101 cases of atypical squamous cells of undetermined significance.

Many women having cervicovaginal smears interpreted as atypical squamous cells of undetermined significance (ASCUS) ultimately prove to harbor squamous intraepithelial lesions (SIL). The question is whether rare cells diagnostic of SIL are present in so-called "atypical" smears, but simply go undetected. To test whether the PAPNET Cytological Screening System, an automated system, can detect the (assumed) presence of such cells, six reviewers independently evaluated PAPNET video images generated for 101 cases conventionally diagnosed as ASCUS. Using PAPNET-identified microscopic coordinates, selected cases were then manually reviewed and reclassified according to consensus opinion. Overall, 35 cases were reclassified as SIL (22 low grade; 13 high grade). Histologic correlations showed 37 of the 101 cases conventionally interpreted as ASCUS carried tissue diagnoses of SIL, (28 low grade; 8 high grade, 1 ungraded). Using PAPNET, 24 of the 37 (65%) corresponding smears were reclassified as SIL (15 low grades; 9 high grade).

Atypical squamous cells of undetermined significance qualified: a follow-up study.

The Bethesda System recommends that the diagnosis of "atypical squamous cells of undetermined significance" (ASCUS) be qualified when possible to indicate whether a reactive process, or a squamous intraepithelial lesion (SIL), is favored. In order to evaluate the utility of this recommendation, 308 cervicovaginal smears diagnosed as ASCUS favoring a reactive (FR) or dysplastic (FD) process were identified. Concurrent or follow-up biopsies and cervicovaginal smear results were reviewed and compared to the follow-up of 103 cervicovaginal smears diagnosed as ASCUS without qualification. A follow-up diagnosis of SIL was found in 46.5%, 29.5% and 26.2% of the ASCUS FD, ASCUS FR, and ASCUS unqualified cases, respectively. A repeated ASCUS diagnosis was found in 20.4%, 21.8%, and 18.4% of the ASCUS FD, ASCUS FR, and ASCUS unqualified cases, respectively. Follow-up of each group was negative for dysplasia in 30.0%, 48.7%, and 54.4% of the ASCUS FD, ASCUS FR, and ASCUS unqualified cases, respectively. These results support the use of an ASCUS FD category for the increased detection of patients with dysplasia. The ASCUS FR category was not helpful in our laboratory. Follow-up studies of qualified ASCUS cases in individual practice settings may be useful in guiding patient management.

Toward objective quality assurance in cervical cytopathology. Correlation of cytopathologic diagnoses with detection of high-risk human papillomavirus types.

Using The Bethesda System, five pathologists independently diagnosed 200 smears that originally had been classified as "atypical," and the results were correlated with concurrent detection of human papillomavirus (HPV) DNA by Southern analysis and by polymerase chain reaction amplification. The smears were reclassified as benign reactive changes (negative), atypical squamous cells of undetermined significance, or squamous intraepithelial lesion (SIL). Exact five-way cytologic agreement was achieved in only 29% of smears, and no slide was diagnosed as atypical squamous cells of undetermined significance by all reviewers. The detection of high-risk types of HPV correlated strongly with the likelihood of a diagnosis of squamous intraepithelial lesion. High-risk HPV types were detected in approximately 60% of smears reclassified as squamous intraepithelial lesion compared with 30% of those reclassified as atypical squamous cells of undetermined significance and 10% of negative smears (P < .001). Every smear unanimously diagnosed by the panel as squamous intraepithelial lesion was associated with detectable HPV DNA, mainly of high-risk types. Low-risk HPV DNA types were found with similar frequency in all diagnostic categories assigned by the reviewers. Based on the consistent relation between high-risk HPV detection and diagnoses according to the Bethesda System, the authors conclude that HPV testing may have an important role in quality assurance in cervical cytopathology.

HPV DNA and the Risk of Squamous Intraepithelial Lesions of the Uterine Cervix in Young Women

A population-based case-control study of college students was undertaken to estimate the effect of a positive clinical test for human papillomavirus (HPV) DNA (the Virapap test) on the rate of squamous intraepithelial lesions (SIL) of the uterine cervix. When age, multiple lifetime sexual partners, and oral contraceptive use were controlled by logistic regression, the adjusted odds ratio (OR) for a positive Virapap test was 7.3 (3.3, 17) for a cytologic diagnosis of SILs and 3.4 (1.4, 8.5) for a cytologic diagnosis of squamous intraepithelial lesions of undetermined significance (equivocal atypia). When case status was defined as patients whose Pap smears were confirmed histologically as high-grade SIL, the adjusted OR was 10.3 (3.3, 32), reflecting the high proportion of individuals with SILs who were harboring high-grade squamous intraepithelial lesions. These results confirm the many previous findings of a strong association between HPV DNA, and demonstrate that strength of the association persists when important confounding variables are controlled. This suggests a causal role for HPV in cervical neogenesis. Believing that HPV infection is a major causal agent for cervical cancer precursors suggests that in this time of rapidly increasing HPV prevalence, especially among young persons, the incidence of cervical neoplasia will rise. This underscores the importance of increasing the availability, usage, and perhaps the frequency of Pap smear screening.

Pathologic evaluation of gynecologic specimens obtained with the Cavitron Ultrasonic Surgical Aspirator (CUSA)

Eighty consecutive gynecologic specimens obtained with the Cavitron Ultrasonic Surgical Aspirator (CUSA) were evaluated pathologically. Fifty specimens were obtained during intraabdominal tumor debulking and thirty resulted from ablation of lower genital tract lesions. In 98% of intraabdominal specimens and in 93% of patients with a history of lower genital tract lesions, the CUSA material permitted an accurate diagnosis. Although artifacts related to cellular thermal injury were ubiquitous, nearly all cases were interpretable with a combination of cytologic (smear, Cytospin, Millipore filter) and histologic (cell block) preparations. Squamous intraepithelial lesions (SILs) of the lower genital tract were better preserved in cell block preparations, whereas intraabdominal adenocarcinomas were readily diagnosed by both cytologic and histologic techniques. Accurate grading of SILs and exclusion of invasion were difficult in some cell blocks due to the fragmented and superficial nature of the samples. Cytologic preparations of lower genital tract lesions often consisted of thick uninterpretable fragments and degenerated single cells that contributed little to the evaluation of SILs. We conclude that examination of CUSA specimens confirmed the surgical removal of pathologic tissue in 96% of cases, but an exact diagnosis Of SILs Was not possible in all Cases.