Human Papillomavirus Antibodies And Future Risk Of Anogenital Cancer: A Nested Case-control Study In The European Prospective Investigation Into Cancer And Nutrition Study

Purpose: Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods: Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results: HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. Conclusion: HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers

Serological and hematological characteristics of Sjogren's syndrome and dry eye syndrome patients using a novel immune serology technique.

ObjectivesTo compare hematologic and serological parameters among patients with Sjogren's syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations.MethodsIn a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the "Immunodot" qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI).ResultsAmong DES patients, only 2% (95%CI: 0.36-6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (PConclusionsSerologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies

Epidermal Growth Factor Receptor-targeted 131I-therapy of Liver Cancer Following Systemic Delivery of the Sodium Iodide Symporter Gene

We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of radioiodine in neuroblastoma tumors after systemic nonviral polyplex-mediated sodium iodide symporter (NIS) gene delivery. In the present study, we used novel polyplexes based on linear polyethylenimine (LPEI), polyethylene glycol (PEG), and the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand to target a NIS-expressing plasmid to hepatocellular carcinoma (HCC) (HuH7). Incubation of HuH7 cells with LPEI-PEG-GE11/NIS polyplexes resulted in a 22-fold increase in iodide uptake, which was confirmed in other cancer cell lines correlating well with EGFR expression levels. Using 123I-scintigraphy and ex vivo γ-counting, HuH7 xenografts accumulated 6.5–9% injected dose per gram (ID/g) 123I, resulting in a tumor-absorbed dose of 47 mGray/Megabecquerel (mGy/MBq) 131Iodide (131I) after intravenous (i.v.) application of LPEI-PEG-GE11/NIS. No iodide uptake was observed in other tissues. After pretreatment with the EGFR-specific antibody cetuximab, tumoral iodide uptake was markedly reduced confirming the specificity of EGFR-targeted polyplexes. After three or four cycles of polyplex/131I application, a significant delay in tumor growth was observed associated with prolonged survival. These results demonstrate that systemic NIS gene transfer using polyplexes coupled with an EGFR-targeting ligand is capable of inducing tumor-specific iodide uptake, which represents a promising innovative strategy for systemic NIS gene therapy in metastatic cancers

EGFR-Targeted Adenovirus Dendrimer Coating for Improved Systemic Delivery of the Theranostic NIS Gene

We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of combined radiovirotherapy after systemic delivery of the theranostic sodium iodide symporter (NIS) gene using a dendrimer-coated adenovirus. To further improve shielding and targeting we physically coated replication-selective adenoviruses carrying the hNIS gene with a conjugate consisting of cationic poly(amidoamine) (PAMAM) dendrimer linked to the peptidic, epidermal growth factor receptor (EGFR)-specific ligand GE11. In vitro experiments demonstrated coxsackie-adenovirus receptor-independent but EGFR-specific transduction efficiency. Systemic injection of the uncoated adenovirus in a liver cancer xenograft mouse model led to high levels of NIS expression in the liver due to hepatic sequestration, which were significantly reduced after coating as demonstrated by 123I-scintigraphy. Reduction of adenovirus liver pooling resulted in decreased hepatotoxicity and increased transduction efficiency in peripheral xenograft tumors. 124I-PET-imaging confirmed EGFR-specificity by significantly lower tumoral radioiodine accumulation after pretreatment with the EGFR-specific antibody cetuximab. A significantly enhanced oncolytic effect was observed following systemic application of dendrimer-coated adenovirus that was further increased by additional treatment with a therapeutic dose of 131I. These results demonstrate restricted virus tropism and tumor-selective retargeting after systemic application of coated, EGFR-targeted adenoviruses therefore representing a promising strategy for improved systemic adenoviral NIS gene therapy

Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer : A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study

Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. Conclusion HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers. (C) 2015 by American Society of Clinical Oncolog