HPV-type has no impact on survival of patients with adenocarcinoma of the uterine cervix
GYNECOLOGIC ONCOLOGY
Authors: Baalbergen, Astrid; Smedts, Frank; Ewing, Patricia; Snijders, Peter J. F.; Meijer, Chris J. L. M.; Helmerhorst, Theo J. M.
Abstract
Objective. To review and characterise by clinical evaluation, immunohistochemistry and HPV typing a group of adenocarcinomas initially diagnosed with primary localisation in the cervix. Furthermore, to assess the prevalence and prognostic significance of HPV genotypes in a large series of HPV positive cervical adenocarcinomas (AC). Methods. One hundred and seventy-one cases of adenocarcinomas (AC) with a primary localisation in the cervix and diagnosed between 1989 and 2008 in the region of Rotterdam, the Netherlands were retrieved. Slides and blocks were reviewed and immunohistochemically stained for CEA and vimentin. HPV testing for high-risk HPV (hrHPV) by PCR (GP5+/16+) and genotyping by reversed line blot were performed. Results. In 113 of 171 patients HPV evaluation was possible. 101 were HPV-positive (89%) and 11 were HPV-negative (11%). The 5-year disease free survival was 80% in the HPV-positive group versus 74% in the HPV-negative group (ns). The distribution of HPV types was type 18 in 55 patients (54%), type 16 in 37 (37%), type 45 in 7 (7%), types 53 and 39 were found in 2 respective patients. 5-year overall-survival in patients with HPV-18 was not significantly worse than in patients with HPV-16 (81 versus 87%). Patients with HPV-45 had a worse 5-year survival, 57%. Conclusions. AC is hrHPV related in most cases (89%) and HPV-18 is the most frequent type (54%). With the exception of HPV-45, HPV-positivity or type in endocervical AC has no significant influence on survival. (C) 2012 Elsevier Inc. All rights reserved.
A PRRSV GP5-Mosaic vaccine: Protection of pigs from challenge and ex vivo detection of IFN gamma responses against several genotype 2 strains
PLOS ONE
Authors: Cui, Junru; O'Connell, Caitlin M.; Costa, Antonio; Pan, Yan; Smyth, Joan A.; Verardi, Paulo H.; Burgess, Diane J.; Van Kruiningen, Herbert J.; Garmendia, Antonio E.
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV), is a highly mutable RNA virus that affects swine worldwide and its control is very challenging due to its formidable heterogeneity in the field. In the present study, DNA vaccines constructed with PRRSV GP5-Mosaic sequences were complexed to cationic liposomes and administered to experimental pigs by intradermal and intramuscular injection, followed by three boosters 14, 28 and 42 days later. The GP5-Mosaic vaccine thus formulated was immunogenic and induced protection from challenge in vaccinated pigs comparable to that induced by a wild type (VR2332) GP5 DNA vaccine (GP5-WT). Periodic sampling of blood and testing of vaccine-induced responses followed. Interferon-gamma (IFN-gamma) mRNA expression by virus-stimulated peripheral blood mononuclear cells (PBMCs) of GP5-Mosaic-vaccinated pigs was significantly higher compared to pigs vaccinated with either GP5-WT or empty vector at 21, 35 and 48 days after vaccination. Cross-reactive cellular responses were also demonstrated in GP5-Mosaic vaccinated pigs after stimulation of PBMCs with divergent strains of PRRSV. Thus, significantly higher levels of IFN-gamma mRNA were detected when PBMCs from GP5-Mosaic-vaccinated pigs were stimulated by four Genotype 2 strains (VR2332, NADC9, NADC30 and SDSU73), which have at least 10% difference in GP5 amino acid sequences, while such responses were recorded only upon VR2332 stimulation in GP5-WT-vaccinated pigs. In addition, the levels of virus-specific neutralizing antibodies were higher in GP5-Mosaic or GP5-WT vaccinated pigs than those in vector-control pigs. The experimental pigs vaccinated with either the GP5-Mosaic vaccine or the GP5-WT vaccine were partially protected from challenge with VR2332, as measured by significantly lower viral loads in sera and tissues and lower lung lesion scores than the vector control group. These data demonstrate that the GP5-Mosaic vaccine can induce cross-reactive cellular responses to diverse strains, neutralizing antibodies, and protection in pigs.