Human papillomavirus (HPV) genotypes and HPV16 variants and risk of adenocarcinoma and squamous cell carcinoma of the cervix

Objective

Human papillomavirus (HPV) genotypes have been extensively studied in uterine cervix squamous cell carcinoma and HPV16 variants have been found to be associated with increased cancer risk, but few reports have been published on genotype distribution and HPV16 variant prevalence in adenocarcinoma tumors. The objective of this study was to analyze viral genotypes and HPV16 intratypic variants in cervical adenocarcinoma and squamous cell carcinoma of Italian women.

Methods

A total of 39 invasive adenocarcinoma and 132 squamous cell carcinoma were reviewed and classified according to the modified WHO classification. HPV sequences were detected by nested PCR, using the broad spectrum consensus-primer pairs MY09/MY11 and the GP5+/GP6+ system, and genotyped by nucleotide sequence analysis. The HPV16-positive cases were amplified with E6-specific oligonucleotides and amplimers subjected to direct nucleotide sequence for variant identification.

Results

The prevalence rate of any HPV infection was 72% in adenocarcinoma, and 85% in cervical squamous cell carcinoma. Among the 140 HPV-positive cancer cases, a total of nine mucosal HPV genotypes (HPV16, 18, 31, 33, 35, 39, 45, 58, 82) epidemiologically classified as carcinogenic or probably carcinogenic viruses were identified. The HPV type 16 was the most common viral type representing 64% and 73% of all infections in adenocarcinoma and squamous cell carcinoma, respectively. The E6 nucleotide sequence analysis of HPV16 isolates allowed the identification of Asian American (AA) variants in 33% of adenocarcinoma and in 20% of squamous cell carcinoma suggesting their stronger association with cancer of glandular origin.

Conclusion

These results suggest that HPV16 has a high prevalence in both invasive adenocarcinoma and squamous cell carcinoma from Italian patients. Moreover this study confirms previous observations, summarized in a systematic review of the literature, on the increased cancer risk of HPV16 AA class in adenoglandular cancer, possibly related to their more oncogenic behavior compared to HPV16 European variants.     

HIV-1 TAT inhibits microglial phagocytosis of Abeta peptide

Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical neuropsychiatric syndrome that has increased in prevalence in the era of highly active antiretroviral therapy (HAART). Several studies demonstrated increased amyloidosis in brains of HIV patients and suggested that there may be a significant number of long-term HIV survivors with co-morbid Alzheimer's disease (AD) in the future. We show HIV-1 Tat protein inhibits microglial uptake of Abeta1-42 peptide, a process that is enhanced by interferon-gamma (IFN-gamma) and rescued by the STAT1 inhibitor (-)-epigallocatechin-3-gallate (EGCG). It is hypothesized that reduced Abeta uptake occurs through IFN-gamma mediated STAT1 activation. This process promotes a switch from a phagocytic to an antigen presenting phenotype in microglia through activation of class II transactivator (CIITA). Additionally, we show that HIV-1 Tat significantly disrupts apolipoprotein-3 (Apo-E3) promoted microglial Abeta uptake. As Tat has been shown to directly interact with the low density lipoprotein (LRP) receptor and thus inhibit the uptake of its ligands including apolipoprotein E4 (Apo-E4) and Abeta peptide in neurons, we further hypothesize that a similar inhibition of LRP may occur in microglia. Future studies will be required to fully characterize the mechanisms underlying IFN-gamma enhancement of HIV-1 Tats disruption of microglial phagocytosis of Abeta and Apo-E3.     

Correlations Between Imaging Biomarkers and Proliferation Index Ki-67 in Lymphomas: A Systematic Review and Meta-Analysis

BackgroundFew studies investigated relationships between positron emission tomography (PET) as well as diffusion-weighted imaging (DWI) with proliferating index Ki-67 in lymphomas. The aim of the present analysis was to review the published results and perform a meta-analysis to provide data on the associations between standardized uptake values (SUV) derived from PET as well as apparent diffusion coefficient (ADC) derived from DWI with Ki-67 index in lymphomas.Materials and MethodsThe MEDLINE library was screened for relationships between PET and DWI with Ki-67 in lymphoma up to October 2018. Overall, 22 studies with 788 patients were identified. The following data were extracted from the literature: authors, year of publication, number of patients, and correlation coefficients. Associations between SUV and Ki-67 were analyzed using Spearman correlation coefficient.ResultsFifteen studies comprising 574 patients were suitable for the analysis between maximum SUV (SUV_max) derived from fluorodeoxyglucose (FDG) PET and Ki-67. The pooled correlation coefficient was r = 0.49 (95% confidence interval [CI], 0.36-0.61). Four studies were included in the analysis between SUV_max derived from fluorothymidine (FLT) PET and Ki-67 index involving 84 patients. The pooled correlation coefficient was r = 0.46 (95% CI, 0.19-0.73). Four studies comprising 130 patients were suitable for the analysis between ADC values derived from DWI and Ki-67. The pooled correlation coefficient was r = −0.25 (95% CI, −0.53 to 0.04).ConclusionSUV_max derived from FDG and FLT PET correlated moderately and approximately equally with Ki-67 index. On the contrary, ADC values only correlated weakly inversely and might not reliably predict Ki-67 index in lymphomas.     

Cerebral spinal fluid contamination of the measurement of the apparent diffusion coefficient of water in acute stroke.

The measurement of the apparent diffusion coefficient (ADC) of water in brains of stroke patients is used in models developed to help distinguish reversible from irreversible ischemic injury. The ADC by conventional methods may be overestimated by the presence of cerebral spinal fluid (CSF) in sulci and perivascular spaces. In this study the hypothesis that DWI with CSF suppression (FLAIR-DWI) would result in different ADC values than those obtained with the conventional DWI technique was investigated. Thirty-one patients with stroke onset of less than 6 hr and an acute lesion on conventional DWI were studied. Both conventional isotropic DWI and FLAIR-DWI were performed using a single-shot echo-planar technique. In all 31 patients, CSF-suppressed ADC was lower than conventional ADC. The mean (SD) of the 31 patients' lesion ADC was 0.64 (0.08) x 10(-3) mm(2) s(-1) with FLAIR-DWI and 0.72 (0.09) x 10(-3) mm(2) s(-1) with conventional DWI (P < 0.001). The overestimation of ADC in conventional DWI corresponded to the percentage of the voxel that contained CSF. Suppression of CSF leads to lesion ADC values that are more homogeneous and more than 15% lower than those obtained with conventional DWI techniques. This suggests that FLAIR-DWI ADC measurements are more accurate than conventional ADC maps.