Isolation, Detection, and Quantification of Cancer Biomarkers in HPV-Associated Malignancies.

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.

Scientific reports. 2017 Jun 12*** epublish ***

Hakan Inan, Shuqi Wang, Fatih Inci, Murat Baday, Richard Zangar, Sailaja Kesiraju, Karen S Anderson, Brian T Cunningham, Utkan Demirci

Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Stanford University School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, 3155 Porter Drive, Palo Alto, CA, 94304, USA., State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China., Pacific Northwest National Laboratory, Richland, WA, USA., Biodesign Institute, School of Life Sciences, Arizona State University, Tempe, AZ, USA., Biodesign Institute, School of Life Sciences, Arizona State University, Tempe, AZ, USA. ., Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA. ., Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Stanford University School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, 3155 Porter Drive, Palo Alto, CA, 94304, USA. .