Sample-to-answer HPV DNA nucleic acid test for cervical cancer screening in Mozambique - PROJECT SUMMARY / ABSTRACT Cervical cancer is the fourth most common cancer in women in the United States. It is a disease that affects young people; 25% of cervical cancer cases in the US are diagnosed in patients between 25-39 years of age, and half occur in patients under age 50. Yet, cervical cancer is preventable. The availability of HPV vaccines and cervical cancer screening, integrated with treatment of precancerous lesions, provides a path to eliminate cervical cancer in the US. However, this requires multiple visits and access to high-quality, timely gynecology and pathology services, which are often unavailable in resource-constrained settings, including rural areas of the US. To date, cervical cancer death rates in the US have not decreased. Current practice for secondary cervical cancer prevention requires three visits, beginning with a first visit for screening. Screening rates have remained stable in the US, with about 75% of patients receiving timely screening. Patients who screen positive require a second diagnostic follow-up, along with a third visit for treatment of any precancerous lesions. This multi-visit paradigm results in loss-to-follow-up and missed opportunities to prevent cancer. The goal of this project is to develop a point-of-care HPV DNA test that can enable cervical cancer screening at the point-of-care in settings with limited medical infrastructure, including rural areas of the United States. We will achieve this goal by adapting and integrating two innovations: 1) an extraction free, multiplexed, isothermal nucleic acid amplification assay; and 2) a fully integrated nucleic acid amplification and lateral flow detection platform called NATFlow. The resulting NATFlow HPV test will be affordable, rapid, and simple to use at the point-of-care. We aim to: 1) adapt existing extraction-free, multiplexed, sample-to-answer Loop-Mediated Isothermal Amplification (LAMP) assays to detect eight high-risk types of HPV on the NATFlow platform and demonstrate technical functionality with 140 provider-collected clinical specimens; (2) evaluate clinical performance of the NATFlow HPV test, first in 558 banked preserved samples and then prospectively in 1,558 women undergoing cervical cancer screening at Hospital Central de Maputo in Mozambique and surrounding community clinics, as this is a population with a high HPV positivity rate, allowing for more efficient test validation; and (3) evaluate factors that affect the uptake of cervical cancer screening using the NATFlow HPV test. We have assembled an interdisciplinary team with extensive collective experience in developing, evaluating, commercializing, and scaling new technologies to prevent cervical cancer. We have a strong record of carrying out translational and implementation research in settings with limited medical infrastructure, including the rural US and Mozambique. Our industrial collaborators have expertise in developing and translating well-designed instrumentation and chemistries for point-of-care tests. Our team is ideally suited to adapt, validate, and prepare to scale the NATFlow HPV test to accelerate efforts to prevent cervical cancer in the US and globally.
