Klaus Schreiber

High risk of human papillomavirus infection and cervical squamous intraepithelial lesions among women with symptomatic human immunodeficiency virus infection

We investigated the relationship of human papillomavirus (by cervicovaginal lavage and Southern blot), human immunodeficiency virus, and squamous intraepithelial lesions in 96 high-risk women in the Bronx, New York. Antibodies for human immunodeficiency virus were detected in 51 (53%) women. Of the 33 women with symptomatic human immunodeficiency virus infection, 23 (70%) had human papillomavirus infection compared with 4 of 18 (22%) asymptomatic women who were human immunodeficiency virus seropositive and 10 of 45 (22%) uninfected women (p less than 0.0001). The rate of squamous intraepithelial lesions was 52% (14 of 27) for women with both viruses detected, 18% (6 of 34) for women with either virus detected, and 9% (3 of 35) for uninfected women. Among symptomatic human immunodeficiency virus-infected women, a strong association between human papillomavirus infection and squamous intraepithelial lesions was demonstrated (odds ratio, 12; 95% confidence interval, 1.3 to 108). Risk was highest for younger women from ethnic or racial minority groups. Advanced human immunodeficiency virus-related disease, with its associated immunosuppression, seems to exacerbate human papillomavirus-mediated cervical cytologic abnormalities. Public health measures are needed to provide Papanicolaou smear screening and appropriate clinical follow-up and treatment for women at high risk for human immunodeficiency virus infection.

Follow-up evaluation of cervicovaginal human papillomavirus infection in adolescents

We performed a second examination for human papillomavirus (HPV) DNA on 51 sexually experienced 13- to 21-year-old (mean = 17.8 years) female patients seen at an urban teaching hospital. Cervicovaginal lavages were performed 6 to 36 months apart (median = 13.3 months) to collect cells for HPV DNA detection and typing by Southern blot hybridization. At the first and second visits, 39.2% (20/51) and 25.5% (13/51) of patients, respectively, were infected with HPV. Collectively, 56.9% (29/51) of patients had at least one positive HPV test result. Although 7.8% (4/51) were infected with HPV at both visits, only one patient had infection with the same HPV type. These findings suggest that although HPV infection is a common sexually transmitted disease, genotype-specific HPV infection detected by Southern blot at two visits was rare.

Malignant mesothelioma of the tunica vaginalis testis: Report of first case with preoperative diagnosis

The cytologic, histologic and ultrastructural features of a malignant carcinomatous mesothelioma of the tunica vaginalis testis in a 30‐year old patient are described. This is the first such case with preoperative diagnosis by cytologic examination of hydrocele fluid and the second with documented history of exposure to asbestos. The identity of the tumor was confirmed by a positive immunoperoxidase reaction directed against mesothelial cells. A review of the previously described ten cases is presented.

Significant reduction in the rate of false-negative cervical smears with neural network-based technology (PAPNET testing system)

False-negative cervical Pap smears may lead to disability or death from carcinoma of the uterine cervix. New computer technology has led to the development of an interactive, neural network-based vision instrument to increase the accuracy of cervical smear screening. The instrument belongs to a new class of medical devices designed to provide computer-aided diagnosis (CADx). To test the instruments performance, 487 archival negative smears (index smears) from 228 women with biopsy-documented high-grade precancerous lesions or invasive cervical carcinoma (index women) were retrieved from the files of 10 participating laboratories that were using federally mandated quality assurance procedures. Samples of sequential negative smears (total 9,666) were retrieved as controls. The instrument was used to identify evidence of missed cytological abnormalities, including atypical squamous or glandular cells of undetermined significance (ASCUS, AGUS), low-grade or high-grade squamous intraepithelial lesions (LSIL, HSIL) and carcinoma. Using the instrument, 98 false-negative index smears were identified in 72 of the 228 index women (31.6%, 95% confidence interval [CI]: 25% to 38%). Disregarding the debatable categories of ASCUS or AGUS, there were 44 women whose false-negative smears disclosed squamous intraepithelial lesions (SIL) or carcinoma (19.3%; 95% CI: 14.2% to 24.4%). Unexpectedly, SILs were also identified in 127 of 9,666 control negative smears (1.3%; 95% CI: 1.1% to 1.5%). Compared with historical performance data from several participating laboratories, the instrument increased the detection rate of SILs in control smears by 25% and increased the yield of quality control rescreening 5.1 times (P < 0.0001). These data provide evidence that conventional screening and quality control rescreening of cervical smears fail to identify a substantial number of abnormalities. A significant improvement in performance of screening of cervical smears could be achieved with the use of the instrument described in this report.

Cervical cytology: The need for routine screeningin the sexually active adolescent

Pelvic examinations, including a Papanicolaou smear of the uterine cervix, were performed on 403 asymptomatic, sexually active adolescent girls aged from 12 to 16 years who were in a youth detention center in New York City. The smears were negative for precancerous abnormalities in 389 girls, but 168 of these had evidence of inflammation or nonspecific atypia. In the remaining 14 smears there was cytologic evidence of early precancerous changes (low-grade cervical intraepithelial neoplasia). The prevalence rate for early neoplastic changes was 35/1,000, far higher than previously reported. Further evaluation of three of these girls, by colposcopy and biopsy, revealed precancerous epithelial abnormalities of varying degrees of severity in two of them. Since all patients screened were sexually active and were asyptomatic, no clinical feature distinguished the 389 with negative cytology from the 14 with intraepithelial neoplasia. Five of the patients with precancerous cellular abnormalities had histories of sexual activity of less than two years. The data suggest that cervical cytologic screening should be incorporated into the routine examination of sexually active female adolescents.

Endometrial carcinoma and its precursors: detection and screening.

This article summarizes the current status of an endometrial cancer detection program in asymptomatic women based on personal experience with 2007 examinees seen during 1979 and 1980. This ongoing feasibility study has shown that occult endometrial carcinoma occurs in approximately 5 of 1000 women age 45 and above and that the disease can be identified by the sampling techniques described in this paper. The identification of high-risk groups is emerging from this prospective study and may lead to a cost-efficient detection protocol that may prove applicable to large scale population screening. The benefits of this study in terms of lowered morbidity and mortality from endometrial carcinoma cannot be documented as yet and require several additional years of follow-up. Perhaps the principal benefit of this study is that it has provided prevalence data for endometrial carcinoma in a hitherto unscreened asymptomatic population against which all future efforts at endometrial cancer detection will have to be measured.

Computed tomography guidance for skeletal biopsy

Computed tomographic (CT) guided biopsy and abscess drainage of multiple organ systems have been well described. Reports of spinal and skeletal applications have been less common. This study describes the use of CT guidance in the biopsy of various skeletal lesions in 46 patients. Forty-one patients had skinny needle aspirations (18 or 22 gauge) and 23 patients had trephine core biopsies. Sites of the lesions included: thoracic spine-15 patients, lumbosacral spine-17 patients, bony pelvis-6 patients, rib-2 patients, and long bones-6 patients. Fast scanners capable of rapid image reconstruction have overcome many constraints. With CT guidance, the physician who performs the procedure receives virtually no ionizing radiation. The exact location of the needle tip is accurately visualized in relation to the lesion being biopsied and to the vital organs.

Flow-microfluorometric analysis of nuclei isolated from various normal and malignant human epithelial tissues. A preliminary report.

In order to obviate some of the technical problems associated with preparation of monocellular cell suspensions required for flow fluorometry, isolation of nuclei from several types of benign and malignant human tissues was undertaken. Satisfactory preparations of nuclei were obtained from epithelia of the uterine cervix and colon and from lung tissue using the citric acid method. The sucrose method was effective with colonic epithelium only. Distribution of deoxyribonucleic acid content in these nuclei was measured based on green fluorescence of acridine orange and red fluorescence of propidium iodide in a Bio-Physics Cytofluorograph. Essentially diploid patterns of deoxyribonucleic acid distribution were observed for all benign samples regardless of tissue origin whereas the malignant samples gave histograms suggestive of abnormal deoxyribonucleic acid distribution. Preliminary observations on distribution of single-stranded nucleic acids using acridine orange red fluorescence showed marked differences between populations of benign and malignant nuclei. Isolated nuclei appear to be suitable for flow-through microfluorometric analysis and offer some significant advantages over intact cells.

THE USE OF A SLIDE SPINNER IN THE ANALYSIS OF CELL DISPERSION

A simple and reliable method of determining the degree of dispersion of a cell suspension has been developed using the Perkin-Elmer Uni-Smear Spinner. Optimum conditions regarding rate and duration of spin, etc., were first ascertained using dispersed cell cultures including human cervical cancer cells as well as gynecologic samples. After spinning, single cells in suspension appeared as isolated cells on the slides. Cell aggregates, on the other hand, remained together. Therefore, the distribution of cells in various sized aggregates could be easily quantitated and the slides retained for future review. This method was used to evaluate the dispersing effects of trypsin, ethylenediaminetetraacetate and and syringing human on human gynecology samples obtained by routine cervical scrapes. None of the dispersion methods has, so far, produced an adequate monodispersed cell suspension without unacceptable cell loss.

Analysis of Atypical Squamous (Glandular) Cells of Undetermined Significance Smears by Neural Network–Directed Review☆

Objective The objective of this study was to evaluate the value of neural network-directed review of smears determined to contain atypical squamous (glandular) cells of undetermined significance to identify those cases most likely to be associated with cervical intraepithelial neoplasia. Methods One hundred sixty smears reported as atypical squamous (glandular) cells of undetermined significance on patients having colposcopy and directed biopsy within 1 year of the smear were identified. The smears were subjected to a neural network-directed review and classified according to findings on this review. The latter findings were related to those obtained on cervical biopsy. Results One hundred sixty smears originally reported as atypical squamous (glandular) cells of undetermined significance were subjected to neural network-directed review. The smears were upgraded in 20.6% of cases. Ninety-one patients were found to have normal biopsies, and 69 had biopsies reported as abnormal. Of the smears in patients with abnormal biopsies, 37.7% were upgraded, whereas only 7.7% of smears from those with normal biopsies were upgraded (P < .001). Nine patients were found to have cervical intraepithelial neoplasia-3 on biopsy. Six of the nine smears (66.7%) taken on these patients were upgraded. Conclusion Neural network-directed analysis of smears conventionally diagnosed as atypical squamous (glandular) cells of undetermined significance will reveal findings suggesting a squamous intraepithelial lesion in a significant number of cases. This approach requires further study because it is a relatively cost-effective means of triaging patients with a cytologic diagnosis of atypical squamous (glandular) cells of undetermined significance.