Karen S. Anderson

Diagnostic Translational Considerations for Global Health Settings: Portable Detection of Human Papillomavirus for Cervical Cancer Screening in India

PURPOSE Translation of diagnostic technology developed at the laboratory bench involves iterations of user feedback and design modifications. Learning about translational requirements early in the design process facilitates the development of feasible prototypes that have a better likelihood of implementation in global health settings. During our development of a portable system to detect human papillomavirus (HPV) for cervical cancer screening in India, we encountered and solved issues related to research translation. We report our findings to help others deploying diagnostic technology for global health. MATERIALS AND METHODS We designed a point-of-care system to process patient samples and diagnose HPV infection in the cervix. We continually shipped components of the system from the United States to our collaborating team in India to assess component condition and usability at the local site. We simultaneously developed HPV isothermal amplification assays that were fit for purpose. Cervical brush samples were used in our portable system for functional validation. RESULTS We found ideal transport methods to ensure component quality and reagent stability through the international shipment chain. Portable systems should be designed as simple as possible for correct usage at the local testing site. Usability tests drove our design improvements from 28% to 93% success rates. We demonstrated proof-of-concept functionality of our portable system for 13 cervical brush samples on-site, with a sensitivity of 100% and specificity of 88.9%. CONCLUSION Issues related to technology transfer for global health settings manifest during distribution and deployment of prototypes. We identified several issues during our synergistic design process and report recommendations on the basis of our experience.

Biomarkers and Strategies for Early Detection of Ovarian Cancer

Abstract Early detection of ovarian cancer remains an important unmet medical need. Effective screening could reduce mortality by 10%–30%. Used individually, neither serum CA125 nor transvaginal sonography (TVS) is sufficiently sensitive or specific. Two-stage strategies have proven more effective, where a significant rise above a woman's baseline CA125 prompts TVS and an abnormal sonogram prompts surgery. Two major screening trials have documented that this strategy has adequate specificity, but sensitivity for early-stage (I–II) disease must improve to have a greater impact on mortality. To improve the first stage, different panels of protein biomarkers have detected cases missed by CA125. Autoantibodies against TP53 have detected 20% of early-stage ovarian cancers 8 months before elevation of CA125 and 22 months before clinical diagnosis. Panels of autoantibodies and antigen–autoantibody complexes are being evaluated with the goal of detecting >90% of early-stage ovarian cancers, alone or in combination with CA125, while maintaining 98% specificity in control subjects. Other biomarkers, including micro-RNAs, ctDNA, methylated DNA, and combinations of ctDNA alterations, are being tested to provide an optimal first-stage test. New technologies are also being developed with greater sensitivity than TVS to image small volumes of tumor. See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible.”