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

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. Methods: 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. Results: 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. Conclusions: 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.

Compact and Filter-Free Luminescence Biosensor for Mobile in Vitro Diagnoses.

We report a sensitive and versatile biosensing approach, LUCID (luminescence compact in vitro diagnostics), for quantitative molecular and cellular analyses. LUCID uses upconversion nanoparticles (UCNPs) as luminescent reporters in mutually exclusive photoexcitation and read-out sequences implemented on a smartphone. The strategy improves imaging signal-to-noise ratios, eliminating interference from excitation sources and minimizing autofluorescence, and thus enables filterless imaging. Here we developed a miniaturized detection system and optimized UCNPs for the system and biological applications. Nanoparticle luminescence lifetime was extended by controlling particle structure and composition. When tested with a range of biological targets, LUCID achieved high detection sensitivity (0.5 pM for protein and 0.1 pM for nucleic acids), differentiated bacterial samples, and allowed profiling of cells. In proof-of-concept clinical use, LUCID demonstrated effective screening of cancer cells in cervical brushing specimens, identifying patients at high risk for malignancy. These results suggest that LUCID could serve as a broadly applicable and inexpensive diagnostic platform.

Cervical cancer: Screening, management, and prevention.

Cervical cancer incidence in the United States is estimated to affect 12,900 women in 2016, with 4,100 deaths. Screening for this cancer with Pap test and adjunct human papillomavirus testing has made cervical cancer a treatable disease. This article reviews screening, treatment recommendations, and prevention for cervical cancer.

Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone.

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts.

Effect of health care disparities on screening.

Significant declines in the incidence and mortality rates of cervical cancer have occurred in the United States since the introduction of the Papanicolaou (Pap) test. Unfortunately, a reduction in the burden of cervical cancer is not equal across all ethnic and racial groups; significant disparities exist. Disparities are reflected not only in mortality and incidence rates, but also in screening rates. We review barriers to screening and effective approaches towards overcoming them. As minority populations increase over the next few decades, it becomes ever more urgent to employ interventions that will reduce the burden of cervical cancer among diverse groups.