The LAST Project and the diagnostic bottom line.

The LAST Project's consensus recommendations for terminology and biomarker use to improve the accuracy and reproducibility of histopathological diagnoses for HPV-associated squamous intraepithelial lesions of the lower anogenital tract are reviewed.

Factors associated with prevalent abnormal anal cytology in a large cohort of HIV-infected adults in the United States.

BACKGROUND: The prevalence of and risk factors for abnormal anal cytology among men and women with human immunodeficiency virus (HIV) infection have not been extensively investigated. METHODS: The Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN study) is a prospective cohort study of HIV-infected patients in 4 US cities. Baseline questionnaires were administered and anal samples for cytology and human papillomavirus (HPV) detection and genotyping were collected. RESULTS: Among 471 men and 150 women (median age, 41 years), 78% of participants were receiving combination antiretroviral therapy, 41% had a CD4(+) cell count of ≥500 cells/µL, and 71% had an HIV RNA viral load of <400 copies/mL. The anal cytology results were as follows: 336 participants (54%) had negative results, 96 participants (15%) had atypical squamous cells, 149 participants (24%) had low-grade squamous intraepithelial lesions, and 40 participants (6%) had high-grade squamous intraepithelial lesions. In a multivariate analysis, abnormal anal cytology was associated with number of high-risk and low-risk HPV types (adjusted odds ratio [AOR] for both, 1.28; P < .001), nadir CD4(+) cell count of <50 cells/µL (AOR, 2.38; P = .001), baseline CD4(+) cell count of <500 cells/µL (AOR, 1.75; P = .004), and ever having receptive anal intercourse (AOR, 2.51; P < .001). CONCLUSION: HIV-infected persons with multiple anal HPV types or a nadir CD4(+) cell count of <50 cells/µL have an increased risk for abnormal anal cytology.

Effect of highly active antiretroviral therapy on the natural history of anal squamous intraepithelial lesions and anal human papillomavirus infection.

The effect of highly active antiretroviral therapy (HAART) on the natural history of anal squamous intraepithelial lesions (ASIL)-the likely anal cancer precursor-and anal human papillomavirus (HPV) infection is unknown. ASIL severity and level of anal HPV DNA were evaluated among HIV-positive men who have sex with men (MSM) for at least 6 months before initiation of HAART. The results were compared with those from a 6-month period after initiation of HAART. Anal swabs for cytology and HPV studies were obtained, followed by high-resolution anoscopy and biopsy. Among men whose most severe pre-HAART diagnosis was atypical squamous cells of undetermined significance or low-grade ASIL, 18% (confidence interval [CI], 6-31%, 7 of 38) progressed and 21% (CI, 8-34%, 8 of 38) regressed 6 months after starting HAART. Seventeen percent (CI, 0-38%, 2 of 12) of study subjects who began with a normal diagnosis developed ASIL. Only 4% (CI, 0-10%, 1 of 28) of study subjects with high-grade ASIL regressed to normal. There was no reduction in the proportion of study subjects who tested positive for HPV DNA or HPV DNA levels after HAART initiation. The ASIL and HPV data were similar to those of the pre-HAART comparison period. These results indicate that HAART has little effect on either ASIL or HPV in the first 6 months after HAART initiation.

Prevalence and risk factors for anal squamous intraepithelial lesions in women.

BACKGROUND: Anal cancers are thought to arise from squamous intraepithelial lesions in the anal canal, and women infected with human immunodeficiency virus-1 (HIV) may be at higher risk of anal cancer. Our aim was to determine the prevalence of human papillomavirus (HPV)-related abnormalities of the anal canal in women and to characterize risk factors for these lesions. METHODS: We evaluated HPV-related abnormalities in 251 HIV-positive and in 68 HIV-negative women. We completed physical examinations and obtained questionnaire data on medical history and relevant sexual practices. Univariate and adjusted relative risks (RRs) and 95% confidence intervals (CIs) were computed using the Mantel-Haenszel procedure and regression techniques. All statistical tests were two-sided. RESULTS: Abnormal anal cytology, including atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions (HSILs), was diagnosed in 26% of HIV-positive and in 8% of HIV-negative women. HSILs were detected by histology or cytology in 6% of HIV-positive and in 2% of HIV-negative women. HIV-positive women showed increased risk of anal disease as the CD4 count decreased (P<.0001) and as the plasma HIV RNA viral load increased (P =.02). HIV-positive women with abnormal cervical cytology had an increased risk of abnormal anal cytology at the same visit (RR = 2.2; 95% CI = 1.4 to 3.3). Abnormal anal cytology in HIV-positive women was associated with anal HPV RNA detected by the polymerase chain reaction and by a nonamplification-based test (RR = 4.3; 95% CI = 1.6 to 11). In a multivariate analysis, the history of anal intercourse and concurrent abnormal cervical cytology also were statistically significantly (P =.05) associated with abnormal anal cytology. CONCLUSIONS: HIV-positive women had a higher risk of abnormal anal cytology than did HIV-negative women with high-risk lifestyle factors. These data provide strong support for anoscopic and histologic assessment and careful follow-up of women with abnormal anal lesions.

Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions.

PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm) vs. normal anoderm (mean, 0.21 vessels/cm; P = 0.0017, Mann-Whitney U test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent) vs. normal anoderm (mean, 14.4 percent), although not significantly (P = 0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13 vs. 19.96 percent, respectively; P = NS, Mann-Whitney U test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.

Risk factors for abnormal anal cytology in young heterosexual women.

Although anal cancers are up to four times more common in women than men, little is known about the natural history of anal human papillomavirus (HPV) infections and HPV-related anal lesions in women. This study reports on the prevalence of and risks for anal cytological abnormalities over a 1-year period in a cohort of young women participating in a study of the natural history of cervical HPV infection. In addition to their regularly scheduled sexual behavior interviews and cervical testing, consenting women received anal HPV DNA and cytological testing. Anal cytology smears were obtained from 410 women whose mean age was 22.5 +/- 2.5 years at the onset of the study. Sixteen women (3.9%) were found to have abnormal anal cytology: 4 women had low-grade squamous intraepithelial lesions (SILs) or condyloma; and 12 women had atypical cells of undetermined significance. Factors found to be significantly associated with abnormal anal cytology were a history of anal sex [odds ratio (OR), 6.90; 95% confidence interval (CI), 1.7-47.2], a history of cervical SILs (OR, 4.13; 95% CI, 1.3-14.9), and a current anal HPV infection (OR, 12.28; 95% CI, 3.9-43.5). The strong association between anal intercourse and the development of HPV-induced SILs supports the role of sexual transmission of HPV in anal SILs. Young women who had engaged in anal intercourse or had a history of cervical SILs were found to be at highest risk.

High incidence of anal high-grade squamous intra-epithelial lesions among HIV-positive and HIV-negative homosexual and bisexual men.

OBJECTIVE: The incidence of anal cancer among homosexual men exceeds that of cervical cancer in women, and HIV-positive homosexual men may be at even higher risk than HIV-negative men. Cervical cancer is preceded by high-grade squamous intra-epithelial lesions (HSIL) and anal HSIL may similarly be the precursor to anal cancer. In this study, we describe the incidence of and risk factors for HSIL in HIV-positive and HIV-negative homosexual and bisexual men. DESIGN: Prospective cohort study of HIV-positive and HIV-negative homosexual men. SETTING: The University of California, San Francisco. PATIENTS: 346 HIV-positive and 262 HIV-negative men enrolled at baseline, 277 HIV-positive and 221 HIV-negative homosexual men followed after baseline. STUDY DESIGN: A questionnaire was administered detailing lifestyle habits, medical history and sexual practices. Anal swabs for cytology and human papillomavirus studies were obtained, followed by biopsies of visible lesions. Human papillomavirus testing was performed using polymerase chain reaction (PCR) and 'hybrid capture'. Blood was obtained for HIV testing and measurement of CD4 levels. MAIN OUTCOME MEASURES: Incident HSIL. RESULTS: HIV-positive men were more likely to develop HSIL than HIV-negative men relative risk (RR), 3.7; 95% confidence interval (CI), 2.6-5.7. Life-table estimates of the 4-year incidence of HSIL was 49% (95% CI, 41-56) among HIV-positive men and 17% (95% CI, 12-23) among HIV-negative men. Among HIV-positive men, those with lower baseline CD4 counts (P = 0.007) and persistent infection with one or more human papillomavirus types, determined using PCR (P = 0.0001), were more likely to develop HSIL. CONCLUSIONS: HIV infection, lower CD4 levels and human papillomavirus infection were associated with high rates of incident HSIL among homosexual men. However, high rates were found at all CD4 levels among HIV-positive men and among HIV-negative men.

Virologic, immunologic, and clinical parameters in the incidence and progression of anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual men.

Anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), but the natural history of ASIL is poorly understood. In this report, we characterize the 2-year incidence and progression of low-grade SIL (LSIL) and high-grade SIL (HSIL) in a cohort study in 346 HIV-positive and 262 HIV-negative homosexual or bisexual men. Subjects were studied at defined intervals using anal cytology, anoscopy with biopsy of visible lesions, human papillomavirus (HPV) testing, HIV serostatus, CD4 level, and data on medical history and lifestyle. The incidence of HSIL within 2 years was 20% in HIV-positive men and 8% in HIV-negative men who were normal at baseline. In total, 62% of HIV-positive and 36% of HIV-negative men with LSIL at baseline progressed to HSIL. The relative risk (RR) for anal disease progression in HIV-positive men was 2.4 (95% confidence interval [CI], 1.8-3.2) when compared with HIV-negative men. The RR increased to 3.1 (95% CI, 2.3-4.1) in HIV-positive men with CD4 counts <200/mm3. Infection with multiple HPV types was a risk factor for anal disease progression in both HIV-positive (RR = 2.0; 95% CI, 1.0-4.1) and HIV-negative (RR = 5.1; 95% CI, 2.3-11) men. The incidence of anal HSIL and progression of LSIL to HSIL within 2 years of follow-up is high in HIV-positive homosexual or bisexual men and to a lesser extent, in HIV-negative men. Men with the above risk factors may be at increased risk of developing anal cancer.

Anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual and bisexual men: prevalence and risk factors.

Anal cancer is more commonly found in homosexual and bisexual men than cervical cancer is in women. Invasive anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), and treatment of ASIL may prevent the development of anal cancer. We characterized the prevalence and risk factors for ASIL in 346 HIV-positive and 262 HIV-negative homosexual men. Anal cytology, biopsy of visible anal lesions, and human papillomavirus (HPV) tests were performed, and data on HIV serostatus, CD4 count, and medical and lifestyle history were collected. ASIL was diagnosed in 36% of HIV-positive men and 7% of HIV-negative men (relative risk [RR] = 5.7; 95% confidence interval [CI], 3.6-8.9). Among HIV-positive men, the RR for ASIL increased with lower CD4 levels but was elevated even in men with CD4 levels >500/mm3 (RR = 3.8; 95% CI, 2.1-6.7) when compared with HIV-negative men. High-level HPV infection, as measured by detection of both hybrid capture (HC) group A and group B types, was another significant risk factor for ASIL in both HIV-positive men (RR = 8.8; 95% CI, 2.3-35) and HIV-negative men (RR = 20; 95% CI, 5.5-71) when compared with HC-negative men. HIV-negative men with anal HPV infection and HIV-positive men, regardless of CD4 level, are at high risk for ASIL.

The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women.

OBJECTIVES: The objectives of this study were to describe the early natural history of human papillomavirus (HPV) infection by examining a cohort of young women positive for an HPV test and to define within this cohort (1) the probability of HPV regression, (2) the risk of having a squamous intraepithelial lesion, and (3) factors that were associated with HPV regression. STUDY DESIGN: The study was a cohort analytic design. An inception cohort of 618 women positive for HPV participated. HPV testing, cytologic evaluation, and colposcopic evaluation were performed at 4-month intervals. HPV testing was characterized for two groups: low risk (five types rarely associated with cancers) and high risk (nine types most commonly associated with cancers). RESULTS: Estimates provided by Kaplan-Meier curves showed that approximately 70% of women were found to have HPV regression by 24 months. Women with low-risk HPV type infections were more likely to show HPV regression than were women with high-risk HPV type infections (log rank test p = 0.002). The relative risk for the development of high-grade squamous intraepithelial lesion (HSIL) was 14.1 (95% confidence interval: 2.3, 84.5) for women with at least three positive tests for high-risk HPV preceding the development of the HSIL compared with that for women with negative tests for high-risk HPV. However, 88% of women with persistent positive HPV tests have not had HSIL to date. No factors associated with high-risk HPV type regression were identified except for a negative association with an incident history of vulvar condyloma (relative risk = 0.5 [95% confidence interval: 0.3 to 0.8]). CONCLUSION: Most young women with a positive HPV test will become negative within a 24-month period. Persistent positive tests with oncogenic HPV types represented a significant risk for the development of HSIL. However, we found that most young women with persistent positive HPV tests did not have cytologically perceptible HSIL over a 2-year period. Factors thought to be associated with the development of HSIL were found not to be important in HPV regression.

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 instrument's 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.

Colposcopic appearance of anal squamous intraepithelial lesions: relationship to histopathology.

PURPOSE: The incidence of anal cancer is increased in men with a history of anal receptive intercourse. Analogous to cervical cancer, whose precursor is cervical high-grade squamous intraepithelial lesion (HSIL), anal cancer may be preceded by anal HSIL. Although not yet proven, detection, follow-up, and treatment of HSIL may prevent development of anal cancer. Cervical colposcopic methodology was used to describe anal lesions and to determine if HSIL could be distinguished from low-grade squamous intraepithelial lesion (LSIL). METHODS: The colposcopic characteristics of 385 biopsied anal lesions were described and correlated with results of histopathology in a cohort of 121 human immunodeficiency virus-positive and 31 human immunodeficiency-negative homosexual/bisexual men with anal lesions followed as part of a longitudinal study of anal squamous intraepithelial lesions. Color, contour, surface, and vascular patterns of anal lesions were analyzed and correlated with histologic diagnosis. RESULTS: Sixty-seven percent of biopsies showed LSIL and 26 percent showed HSIL. The positive predictive value for anal HSIL in lesions with characteristics typical of cervical LSIL was 7.7 percent (95 percent confidence interval, 1.8-14), whereas the positive predictive value for anal HSIL in lesions with characteristics typical of cervical HSIL was 49 percent (95 percent confidence interval, 40-58). CONCLUSIONS: The colposcopic appearance of different grades of anal squamous intraepithelial lesions was similar to those described for the cervix. Incorporation of colposcopy into assessment of anal disease could aid in distinguishing anal LSIL from HSIL.

Comparison of conventional cytologic smears and ThinPrep preparations from the anal canal.

OBJECTIVE: To compare anal cytology prepared via conventional methods and the ThinPrep processor. STUDY DESIGN: Cells from the anal canal were collected using a moistened swab. One hundred thirty-six samples were collected from 133 gay or bisexual men; 102 were human immunodeficiency virus seropositive. A conventional smear was prepared and fixed in 95% ethanol. The residual cells on the swab were collected for thin-layer preparation using the Cytyc processor. RESULTS: The diagnoses made from the conventional smears and thin layers agreed in 113 of 136 cases. An additional 19 cases were classified within one diagnostic category of each other. Two cases of low grade squamous epithelial lesion (SIL) diagnosed on the ThinPrep were judged negative on the conventional smear. Similarly, two cases of low grade SIL diagnosed on the conventional smear were judged negative on the thin-layer preparations. Rectal columnar cells were present on 127 of the ThinPrep samples but on only 113 of the conventional smears. CONCLUSION: ThinPrep and conventional smears of the anal canal yielded similar diagnoses. Rectal columnar cells were more frequently encountered on the thin layers; their presence is an indication that the rectal transformation zone may have been adequately sampled. In addition, the ThinPrep technique reduces fecal and bacterial contamination and air-drying artifact, which frequently hinder cytologic evaluation of the anal canal.

Anal cytological abnormalities and anal HPV infection in men with Centers for Disease Control group IV HIV disease.

OBJECTIVE: To characterise risk factors for abnormal and cytology and anal human papilloma virus (HPV) infection in homosexual/bisexual men with advanced HIV related immunosuppression. DESIGN: Cross sectional study of men with Centers for Disease Control group IV HIV disease. SETTING: The University of California San Francisco, AIDS Clinic. PATIENTS: 129 homosexual or bisexual men with group IV HIV disease. METHODS: A questionnaire was administered detailing tobacco, alcohol and recreational drug use, medical history, and sexual practices. Anal swabs for cytology and HPV studies were obtained, as was blood for CD4 levels. MAIN OUTCOME MEASURES: Abnormal anal cytology and anal HPV infection. RESULTS: Abnormal anal cytology was detected in 39% of subjects and anal HPV infection in 93% as measured by polymerase chain reaction (PCR). Risk factors for abnormal cytology in multivariate analysis included HPV 16/18 infection (measured by PCR, RR = 2.1, 95% CI = 1.2-3.5) and intravenous drug use (RR = 1.8, 95% CI = 1.2-2.7). Infection with HPV 6/11 also had significantly elevated RRs in a separate model. Cigarette smoking, alcohol use, recreational drug use, and low CD4 level were associated with abnormal anal cytology in univariate analysis, as was infection with multiple HPV types and high levels of hybrid capture group B viral DNA. CONCLUSIONS: Anal cytological abnormalities and HPV infection are common among homosexual/bisexual men with group IV HIV disease. In this study population, the main risk factors for abnormal cytology were HPV infection and intravenous drug use.

Polyomavirus-induced interstitial nephritis in two renal transplant recipients: case reports and review of the literature.

We present two case reports of renal polyomavirus infection leading to renal allograft dysfunction, review the literature of this entity, and discuss the role of specific immunosupressives. Histologically, the virus caused an interstitial infiltrate composed of plasma cells and lymphocytes, interstitial fibrosis, and tubular atrophy. Viral inclusions were seen within tubular cells on light microscopy. Electron microscopy showed viral particles of 40 to 50 nm in a characteristic paracrystalline array. Both patients had been on FK-506-based immunosuppression. In both patients, the virus appeared to clear histologically and renal function stabilized when the patients were converted to cyclosporine-based immunosuppression. Contrary to prior reports, our patients have not lost their grafts and continue to have stable, albeit reduced, graft function at 2.5 years and 4.5 years following the initial diagnosis of renal polyomavirus infection.

Anal cytology as a screening tool for anal squamous intraepithelial lesions.

Anal squamous intraepithelial lesions (ASIL) are common in homosexual and bisexual men, and high-grade ASIL (HSIL) in particular may represent an anal cancer precursor. Cervical cytology is a useful screening tool for detection of cervical HSIL to prevent cervical cancer. To assess anal cytology as a screening tool for anal disease, we compared anal cytology with anoscopy and histopathology of anal biopsies. A total of 2958 anal examinations were performed on 407 HIV-positive and 251 HIV-negative homosexual or bisexual men participating in a prospective study of ASIL. The examination consisted of a swab for anal cytology and anoscopy with 3% acetic acid and biopsy of visible lesions. Defining abnormal cytology as including atypical squamous cells of undetermined significance and ASIL, the sensitivity of anal cytology for detection of biopsy-proven ASIL was 69% (95% confidence interval: 60 to 78) in HIV-positive and 47% (95% confidence interval; 26 to 68) in HIV-negative men at their first visit and was 81% and 50%, respectively, for all subsequent visits combined. The absence of columnar cells did not affect the sensitivity, specificity, or predictive value of anal cytology. Anal cytology may be a useful screening tool to detect ASIL, particularly in HIV-positive men. The grade of disease on anal cytology did not always correspond to the histologic grade, and anal cytology should be used in conjunction with histopathologic confirmation.

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.

Postictal pulmonary edema requires pulmonary vascular pressure increases.

The pathogenesis of neurogenic pulmonary edema has been debated for many years. Whether cardiogenic mechanisms and increased pulmonary vascular pressures are primary or even necessary for the production of pulmonary edema has been argued. We used postictal pulmonary edema to study this problem in a sheep model of neurogenic pulmonary edema with bicucullin-induced status epilepticus. Seizure-induced increases in pulmonary vascular pressures were averted with a reservoir system to maintain left atrial pressure (LAP) and pulmonary artery pressure (PAP) at preseizure levels. No increase in lung lymph flow occurred during seizures, in contrast to the doubling of lung lymph flow that occurred during seizures when ictal pulmonary vascular hypertension was not blocked. These data support a primary role of pulmonary vascular pressure increases in the production of neurogenic pulmonary edema.

Anal and cervical human papillomavirus infection and risk of anal and cervical epithelial abnormalities in human immunodeficiency virus-infected women.

OBJECTIVE: To determine the prevalence of anal and cervical infection with human papillomavirus (HPV) and cytologic abnormalities and to examine the relation among HPV infection, cytologic abnormalities, and human immunodeficiency virus (HIV) serostatus. METHODS: Anal and cervical Papanicolaou tests, HPV dot blot tests, and polymerase chain reaction (PCR) tests for HPV were performed concurrently in a cross-sectional study of 114 women enrolled in a community-based study of HIV infection. RESULTS: Cervical HPV infection was associated with HIV serostatus by both dot blot (odds ratio [OR] 4.2, 95% confidence interval [CI] 1-25) and PCR (OR 8.9, 95% CI 3.2-27). Anal HPV infection was twice as frequent as cervical and also was associated with HIV by dot blot (OR 2.5, 95% CI 0.9-7) and PCR (OR 2.6, 95% CI 1.03-6.8). Eleven percent (11 of 96) of cervical cytologies were abnormal and were associated with HIV (OR 6.1, 95% CI 1.2-60.5). Fourteen percent (15 of 109) of anal cytologies were abnormal and were associated with HIV (OR 3.4, 95% CI 0.9-15.5). Among HIV-seropositive women, epithelial abnormalities were associated with lower mean CD4+ cell counts when HPV DNA was detected by dot blot at either the cervix (P = .04) or anus (P = .009). Independent predictors for cervical epithelial abnormalities were HPV DNA positivity by dot blot (OR 32.1, 95% CI 2.9-353.9) and positive HIV serostatus with CD4+ cell count below 250 cells/mm3 (OR 126.8, 95% CI 7.5-2132.6). CONCLUSIONS: Human papillomavirus-associated epithelial abnormalities are associated with immune suppression among HIV-infected women. Anal HPV infection and disease is at least as common as cervical infection and disease among HIV-seropositive women.

Comparison between colposcopic, cytologic, and histologic findings in women positive and negative for human papillomavirus DNA.

Little is known about the role of detection of human papillomavirus (HPV) DNA in exfoliated cells of the cervix in aiding the colposcopic diagnosis of cervical lesions. The purpose of our study was to compare the colposcopic findings of young women who were positive and negative for HPV DNA. Eighty-four women aged 13-22 years attending family planning clinics were examined colposcopically with the aide of acetic acid and Lugol's solution and without knowledge of HPV DNA status. Lesions identified were given scores based on the severity of observed colposcopic changes. Samples for cytology and HPV DNA testing, which included types 6, 11, 16, 18, 31, 33, and 35, were obtained at the time of the examination. Biopsies were performed on women with significant lesions identified on examination or with cytology suggestive of neoplasia. Students t-test and chi 2 analysis were performed to compare colposcopic variables and HPV DNA type. Of the 84 women examined, 17 were positive for HPV DNA; 9 had type 16/18. The average length of sexual activity was 2.7 years. Women with HPV 16/18 had a mean of 1.7 lesions visible at colposcopy compared to 0.7 lesions visible in those negative for HPV 16/18 (this included HPV DNA negative women and women positive for HPV types 6, 11, 31, 33, and 35) (p < 0.001). Women who were positive for HPV 16/18 also had higher lesional scores than the HPV 16/18-negative group (3.4 versus 1.0, respectively, p < 0.001). All four women who had dysplasia either on cytology or histology were positive for type 16/18.(ABSTRACT TRUNCATED AT 250 WORDS)