This study was designed to determine the prevalence and risk factors for anal squamous intraepith... more This study was designed to determine the prevalence and risk factors for anal squamous intraepithelial lesions and human papillomavirus infection in a rural population of HIV-infected males. A cross-sectional study was performed. Risk factors were collected. Anal Papanicolaou smear and human papillomavirus screening for oncogenic types were performed. Of 211 eligible male patients, 149 (70.6 percent) participated. HIV transmission risk was predominantly males who have sex with males (82 percent). The mean duration of HIV infection was 9.9 years. Ninety (60 percent) males had abnormal anal cytology, including atypical cells of unknown significance 40 (26 percent), low-grade squamous intraepithelial lesions 28 (19 percent), and high-grade squamous intraepithelial lesions 22 (15 percent). Human papillomavirus was detected in 61 percent. Binary logistic regression adjusted risks for abnormal anal cytology included: males who have sex with males (P<0.001), human papillomavirus infection (P<0.001), history of anogenital warts (P=0.014), and the mean lowest CD4 count (abnormal cytology, 158 (standard deviation, 135), negative cytology, 208 (standard deviation, 180; P=0.017)). Twenty-two patients with high-grade squamous intraepithelial lesions underwent colorectal surgical examination and anoscopy. Two (10 percent) were found to have invasive squamous-cell carcinoma and three (15 percent) others had mass lesions with high-grade squamous intraepithelial lesions. Anal squamous intraepithelial lesions and oncogenic human papillomavirus are highly prevalent in males infected with HIV and living in a rural setting.
The demonstration of human papillomavirus (HPV) in 99.7% of cervical carcinoma surgical specimens... more The demonstration of human papillomavirus (HPV) in 99.7% of cervical carcinoma surgical specimens from around the world required investigations by multiple alternative polymerase chain reaction (PCR) assays. A similar approach may therefore be necessary to best characterize HPV prevalence and genotype distribution among cervical cytology samples. In an earlier study, 752 of 799 (94.1%) abnormal and 82 of 300 (27.3%) normal cytology specimens tested HPV positive after PCR using GP5+/6+primers. This study has reinvestigated the "HPV negative" abnormal samples (20 atypical squamous cells of undetermined significance, 5 low-grade squamous intraepithelial lesion, 14 atypical squamous cells, cannot exclude HSIL, 6 high-grade squamous intraepithelial lesion) and an age-matched cohort of "HPV negative" normal (negative for an intraepithelial lesion or malignancy) samples by PCR using PGMY09/11, FAP59/64, and LCR-E7 primers. PGMY09/11-GP5+/6+ nested PCR was performed on samples that were HPV negative by PGMY09/11 PCR. After the first 3 assays, HPV was detected in 41 of 45 (91.1%) abnormal and in 10 of 47 (21.3%) normal samples (P<0.0001). Eighteen HPV genotypes were detected and in some samples the genotype that was identified differed between the tests. The nondetection of common HPV genotypes (eg, HPVs 6, 11, 16, and 18) was notable. High-grade histopathology was found for 2 patients with HPV52-positive cytopathology. Combined with our earlier study, HPV (40 different genotypes) is shown in 99.5% of abnormal samples (99.8% inclusive of the nested PCR data). These findings show that HPV genotype and prevalence estimates are dependent on the method(s) of detection and indicate that suboptimal analytical sensitivity for one or more of the less common high-risk HPV genotypes could lead to impaired clinical sensitivity. HPV may be causal in almost every instance of abnormal cervical cytology; however, passenger HPV that is incidental to an abnormality may also have been detected.
The Cytyc ThinPrep Imaging System was FDA approved based on a multi-institutional clinical trial,... more The Cytyc ThinPrep Imaging System was FDA approved based on a multi-institutional clinical trial, in which the HSIL+ prevalence rate was 0.7%. This study determines the effectiveness of the Imager in clinical practice at an academic medical center with a historical HSIL+ rate of 0.25%. Cytological interpretations were compared for two 12-month periods pre- and post-Imager implementation. Data was compiled by cytologic diagnoses, and variations in prevalence rates were analyzed for statistical significance. Interpretations of ASC-US, ASC-H, and LSIL were correlated with Digene Hybrid Capture2 High Risk HPV DNA testing; interpretations of ASC-H, LSIL, and HSIL+ were correlated with subsequent surgical follow-up. ASC-US, ASC-H, and LSIL detection rates increased 34, 48, and 29%, respectively, with the Imager (P<0.001); whereas the detection of HSIL increased 24% (P<0.051). Surgical correlation revealed no statistical differences in the positive predictive value (PPV) for ASC-H and LSIL. However, an increase in the PPV of HSIL was found (P<0.05). High risk HPV results were lower for ASC-US (P<0.001), but statistically equivalent for ASC-H and LSIL. Results of surgical correlation and HPV testing validated an increase in detection rates of ASC-H, LSIL, and HSIL, as well as increased PPV of HSIL with the ThinPrep Imaging System.
Sequential tracheal aspirates from 39 neonates with hyaline membrane disease were examined to cor... more Sequential tracheal aspirates from 39 neonates with hyaline membrane disease were examined to correlate cytological findings with the development of bronchopulmonary dysplasia (BPD). A total of 224 tracheal aspirates were examined from these infants, 15 of whom developed BPD as diagnosed by conventional clinical and radiological criteria. Hyperplastic and metaplastic epithelial changes were observed in all infants studied. Dysplastic changes occurred in 14 of 15 who developed BPD, and 14 of 24 who had a normal outcome (P less than 0.02). The exfoliation of dysplastic metaplastic bronchial cells was thus 95% specific and 71% sensitive for the subsequent development of BPD. Factors associated with the development of BPD were very low birth weight and gestational age, persistence of a patent ductus arteriosus, high peak inspiratory pressure (cm of H2O/kg), prolonged assisted ventilation, and rapidity of development of class III (dysplastic) changes in tracheal aspirates.
A previously unreported high incidence of endoscopically identifiable, diffuse, largely nonulcera... more A previously unreported high incidence of endoscopically identifiable, diffuse, largely nonulcerative esophagitis, is described in a selected population of Southern African blacks at risk of cancer of the esophagus. This is comparable with findings in similar groups in Iran and China. The incidence of dysplasia and "early" cancer is still undefined in South Africa.
This study was designed to determine the prevalence and risk factors for anal squamous intraepith... more This study was designed to determine the prevalence and risk factors for anal squamous intraepithelial lesions and human papillomavirus infection in a rural population of HIV-infected males. A cross-sectional study was performed. Risk factors were collected. Anal Papanicolaou smear and human papillomavirus screening for oncogenic types were performed. Of 211 eligible male patients, 149 (70.6 percent) participated. HIV transmission risk was predominantly males who have sex with males (82 percent). The mean duration of HIV infection was 9.9 years. Ninety (60 percent) males had abnormal anal cytology, including atypical cells of unknown significance 40 (26 percent), low-grade squamous intraepithelial lesions 28 (19 percent), and high-grade squamous intraepithelial lesions 22 (15 percent). Human papillomavirus was detected in 61 percent. Binary logistic regression adjusted risks for abnormal anal cytology included: males who have sex with males (P<0.001), human papillomavirus infection (P<0.001), history of anogenital warts (P=0.014), and the mean lowest CD4 count (abnormal cytology, 158 (standard deviation, 135), negative cytology, 208 (standard deviation, 180; P=0.017)). Twenty-two patients with high-grade squamous intraepithelial lesions underwent colorectal surgical examination and anoscopy. Two (10 percent) were found to have invasive squamous-cell carcinoma and three (15 percent) others had mass lesions with high-grade squamous intraepithelial lesions. Anal squamous intraepithelial lesions and oncogenic human papillomavirus are highly prevalent in males infected with HIV and living in a rural setting.
The demonstration of human papillomavirus (HPV) in 99.7% of cervical carcinoma surgical specimens... more The demonstration of human papillomavirus (HPV) in 99.7% of cervical carcinoma surgical specimens from around the world required investigations by multiple alternative polymerase chain reaction (PCR) assays. A similar approach may therefore be necessary to best characterize HPV prevalence and genotype distribution among cervical cytology samples. In an earlier study, 752 of 799 (94.1%) abnormal and 82 of 300 (27.3%) normal cytology specimens tested HPV positive after PCR using GP5+/6+primers. This study has reinvestigated the "HPV negative" abnormal samples (20 atypical squamous cells of undetermined significance, 5 low-grade squamous intraepithelial lesion, 14 atypical squamous cells, cannot exclude HSIL, 6 high-grade squamous intraepithelial lesion) and an age-matched cohort of "HPV negative" normal (negative for an intraepithelial lesion or malignancy) samples by PCR using PGMY09/11, FAP59/64, and LCR-E7 primers. PGMY09/11-GP5+/6+ nested PCR was performed on samples that were HPV negative by PGMY09/11 PCR. After the first 3 assays, HPV was detected in 41 of 45 (91.1%) abnormal and in 10 of 47 (21.3%) normal samples (P<0.0001). Eighteen HPV genotypes were detected and in some samples the genotype that was identified differed between the tests. The nondetection of common HPV genotypes (eg, HPVs 6, 11, 16, and 18) was notable. High-grade histopathology was found for 2 patients with HPV52-positive cytopathology. Combined with our earlier study, HPV (40 different genotypes) is shown in 99.5% of abnormal samples (99.8% inclusive of the nested PCR data). These findings show that HPV genotype and prevalence estimates are dependent on the method(s) of detection and indicate that suboptimal analytical sensitivity for one or more of the less common high-risk HPV genotypes could lead to impaired clinical sensitivity. HPV may be causal in almost every instance of abnormal cervical cytology; however, passenger HPV that is incidental to an abnormality may also have been detected.
The Cytyc ThinPrep Imaging System was FDA approved based on a multi-institutional clinical trial,... more The Cytyc ThinPrep Imaging System was FDA approved based on a multi-institutional clinical trial, in which the HSIL+ prevalence rate was 0.7%. This study determines the effectiveness of the Imager in clinical practice at an academic medical center with a historical HSIL+ rate of 0.25%. Cytological interpretations were compared for two 12-month periods pre- and post-Imager implementation. Data was compiled by cytologic diagnoses, and variations in prevalence rates were analyzed for statistical significance. Interpretations of ASC-US, ASC-H, and LSIL were correlated with Digene Hybrid Capture2 High Risk HPV DNA testing; interpretations of ASC-H, LSIL, and HSIL+ were correlated with subsequent surgical follow-up. ASC-US, ASC-H, and LSIL detection rates increased 34, 48, and 29%, respectively, with the Imager (P<0.001); whereas the detection of HSIL increased 24% (P<0.051). Surgical correlation revealed no statistical differences in the positive predictive value (PPV) for ASC-H and LSIL. However, an increase in the PPV of HSIL was found (P<0.05). High risk HPV results were lower for ASC-US (P<0.001), but statistically equivalent for ASC-H and LSIL. Results of surgical correlation and HPV testing validated an increase in detection rates of ASC-H, LSIL, and HSIL, as well as increased PPV of HSIL with the ThinPrep Imaging System.
Sequential tracheal aspirates from 39 neonates with hyaline membrane disease were examined to cor... more Sequential tracheal aspirates from 39 neonates with hyaline membrane disease were examined to correlate cytological findings with the development of bronchopulmonary dysplasia (BPD). A total of 224 tracheal aspirates were examined from these infants, 15 of whom developed BPD as diagnosed by conventional clinical and radiological criteria. Hyperplastic and metaplastic epithelial changes were observed in all infants studied. Dysplastic changes occurred in 14 of 15 who developed BPD, and 14 of 24 who had a normal outcome (P less than 0.02). The exfoliation of dysplastic metaplastic bronchial cells was thus 95% specific and 71% sensitive for the subsequent development of BPD. Factors associated with the development of BPD were very low birth weight and gestational age, persistence of a patent ductus arteriosus, high peak inspiratory pressure (cm of H2O/kg), prolonged assisted ventilation, and rapidity of development of class III (dysplastic) changes in tracheal aspirates.
A previously unreported high incidence of endoscopically identifiable, diffuse, largely nonulcera... more A previously unreported high incidence of endoscopically identifiable, diffuse, largely nonulcerative esophagitis, is described in a selected population of Southern African blacks at risk of cancer of the esophagus. This is comparable with findings in similar groups in Iran and China. The incidence of dysplasia and "early" cancer is still undefined in South Africa.
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Papers by Gladwyn Leiman