Objectives We hypothesized that viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer (HPVOPC). Materials and methods We conducted a multicenter study to measure HPV16-specific IgG among patients with HPVOPC, their long-term sexual partners, and healthy volunteers. Risk factor surveys and rinse and gargle specimens were collected. Peripheral blood samples at diagnosis were evaluated for IgG Abs to HPV16 antigens using a programmable ELISA assay. Predictors for HPV16 serologic responses were evaluated using univariate and multivariable linear regression. Results 116 patients with HPVOPC, 43 partners, and 81 healthy volunteers were enrolled and had baseline sera for analysis. Cases were primarily male (90%), with a median age of 56 years. Abs to E1, E2, E6 or E7 antigens were detected more often in HPVOPC compared with volunteers or partner sera (p<0.0001). HPV16 Abs to at least one early protein (E1, E2, E4, E5, E6, or E7) were detected in the sera of 90.6% of cases, 0% of partners and 7.4% of healthy volunteers. Gender, race, sexual behavior, and viral integration were not associated with antibody response. Younger age and higher oral HPV16 copy number were associated with higher HPV16 E6 and NE2 antibody levels. Conclusions HPV16 seroreactivity is commonly detected among patients with HPVOPC at diagnosis, but not among partners or healthy volunteers. Seroreactivity among cases are correlated with viral load and stage and not with other demographic or behavioral factors. Positive HPV16 serology was strongly associated with HPV 16 oropharyngeal cancer.
Human Papillomavirus (HPV) infection has been recognized as the main etiologic factor in the development of various cancers including penile, vulva, oropharyngeal and cervical cancers. In the development of cancer, persistent HPV infections induce E6 and E7 oncoproteins, which promote cell proliferation and carcinogenesis resulting elevated levels of host antibodies (e.g., anti-HPV16 E7 antibody). Currently, these cancers are clinically diagnosed using invasive biopsy-based tests, which are performed only in centralized labs by experienced clinical staff using time-consuming and expensive tools and technologies. Therefore, these obstacles constrain their utilization at primary care clinics and in remote settings, where resources are limited. Here, we present a rapid, inexpensive, reliable, easy-to-use, customized immunoassay platform following a microfluidic filter device to detect and quantify anti-HPV16 E7 antibodies from whole blood as a non-invasive assisting technology for diagnosis of HPV-associated malignancies, especially, at primary healthcare and remote settings. The platform can detect and quantify anti-HPV16 E7 antibody down to 2.87 ng/mL. We further validated our immunoassay in clinical patient samples and it provided significantly high responses as compared to control samples. Thus, it can be potentially implemented as a pretesting tool to identify high-risk groups for broad monitoring of HPV-associated cancers in resource-constrained settings.
Point-of-care molecular diagnostics can provide efficient and cost-effective medical care, and they have the potential to fundamentally change our approach to global health. However, most existing approaches are not scalable to include multiple biomarkers. As a solution, we have combined commercial flat panel OLED display technology with protein microarray technology to enable high-density fluorescent, programmable, multiplexed biorecognition in a compact and disposable configuration with clinical-level sensitivity. Our approach leverages advances in commercial display technology to reduce pre-functionalized biosensor substrate costs to pennies per cm2. Here, we demonstrate quantitative detection of IgG antibodies to multiple viral antigens in patient serum samples with detection limits for human IgG in the 10 pg/mL range. We also demonstrate multiplexed detection of antibodies to the HPV16 proteins E2, E6, and E7, which are circulating biomarkers for cervical as well as head and neck cancers.
Although basiliximab and rabbit anti-thymocyte globulin (ATG) are effective in delaying and reducing the incidence of acute rejection (AR) thus improving short-term graft survival, their impact on long-term graft survival has not been well established in renal transplant recipients. To evaluate the long-term efficacy after induction therapy with ATG/basiliximab in renal transplant recipients, we studied retrospectively 86 renal transplant recipients of living donor renal transplantation from 2003 to 2006; of them, 42 patients received induction with ATG three doses of 50 mg, 25 mg, 25 mg/day on 0, 1 and 2 post-operative days (POD) and 44 age-matched patients received induction with basiliximab (20 mg/day on 0 and 4 PODs). All the patients received tacrolimus, mycophenolate mofetil and corticosteroids as maintenance immunosuppressive therapy. Demographic characteristics were similar between both groups. Patient survival at 5 years was 90.5% in the ATG group and 84.1% in the basiliximab group, while graft survival was 83.4% and 77.3%, respectively. The incidence of acute rejection was 14.2% and 18.1% in the ATG and the basiliximab groups, respectively. The estimated mean glomerular filtration rates at 5 years post-transplantation was 52.1 mL/min and 49.1 mL/min and the mean serum creatinine levels were 1.55 ± 0.37 and 1.66 ± 0.51 mg/dL in the ATG and basiliximab groups, respectively. A low incidence of tuberculosis and cytomegalovirus (CMV) was observed in the ATG group. There were no significant differences between the two groups, and both induction regimens assured a safe and effective treatment and were associated with similar excellent long-term patient and graft survival.
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