Point-of-care cervical cancer screening using deep learning-based microholography.

Journal: Theranostics
Published Date:

Abstract

Most deaths (80%) from cervical cancer occur in regions lacking adequate screening infrastructures or ready access to them. In contrast, most developed countries now embrace human papillomavirus (HPV) analyses as standalone screening; this transition threatens to further widen the resource gap. We describe the development of a DNA-focused digital microholography platform for point-of-care HPV screening, with automated readouts driven by customized deep-learning algorithms. In the presence of high-risk HPV 16 or 18 DNA, microbeads were designed to bind the DNA targets and form microbead dimers. The resulting holographic signature of the microbeads was recorded and analyzed. The HPV DNA assay showed excellent sensitivity (down to a single cell) and specificity (100% concordance) in detecting HPV 16 and 18 DNA from cell lines. Our deep learning approach was 120-folder faster than the traditional reconstruction method and completed the analysis in < 2 min using a single CPU. In a blinded clinical study using patient cervical brushings, we successfully benchmarked our platform's performance to an FDA-approved HPV assay. Reliable and decentralized HPV testing will facilitate cataloguing the high-risk HPV landscape in underserved populations, revealing HPV coverage gaps in existing vaccination strategies and informing future iterations.

Authors

  • Divya Pathania
    Center for Systems Biology , Massachusetts General Hospital , Boston , Massachusetts 02114 , United States.
  • Christian Landeros
    Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Lucas Rohrer
    Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Victoria D'Agostino
    Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Seonki Hong
    Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Ismail Degani
    Center for Systems Biology , Massachusetts General Hospital , Boston , Massachusetts 02114 , United States.
  • Maria Avila-Wallace
    Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Misha Pivovarov
    Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Thomas Randall
    Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Ralph Weissleder
    Center for Systems Biology , Massachusetts General Hospital , Boston , Massachusetts 02114 , United States.
  • Hakho Lee
    Center for Systems Biology , Massachusetts General Hospital , Boston , Massachusetts 02114 , United States.
  • Hyungsoon Im
    Center for Systems Biology , Massachusetts General Hospital , Boston , Massachusetts 02114 , United States.
  • Cesar M Castro
    Center for Systems Biology , Massachusetts General Hospital , Boston , Massachusetts 02114 , United States.