Point-of-care HPV mRNA test for cervical cancer screening in low-resource settings

Abstract:

There is a significant need to improve global access to cervical cancer screening. Globally, approximately

570,000 women are diagnosed with and 311,000 women die from cervical cancer each year. Nearly 90 percent

of cervical cancer deaths occur in low- and middle-income countries (LMICs), due mainly to challenges in

implementing effective screening programs. Likewise, cervical cancer rates in medically underserved areas in

the US remain high. For example, in the Rio Grande Valley of Texas, cervical cancer incidence rates are 55%

higher than the US average, and approximately 10% of eligible women are screened. There is broad consensus

that high-risk human papillomavirus (hrHPV) testing is the best approach to improve global screening efforts. An

HPV biomarker that provides excellent sensitivity and better specificity than DNA is hrHPV mRNA. However,

currently available hrHPV mRNA testing remains too complex and costly (e.g. >$45,000 for equipment and

roughly $74 per test) for effective implementation into low-resource and medically underserved settings.

Advances in isothermal amplification and lateral flow detection offer an opportunity to develop a point-of-care

(POC) hrHPV mRNA test that is accurate, affordable, and can be performed in low-resource settings. The goal

of this proposal is to combine isothermal amplification and lateral flow detection within an integrated point-of-

care device to dramatically lower the cost of hrHPV mRNA testing. We will develop a low-cost, POC hrHPV E7

mRNA test that requires minimal laboratory equipment and performs as well as commercial RNA tests.

Isothermal amplification reduces the instrumentation cost and complexity typically associated with nucleic acid

amplification requiring only a single-temperature heater. Lateral flow detection integrates sample manipulation

processes and wicks all detection reagents past pre-defined test zones, producing a simple, colorimetric readout.

Our proposed proof-of-concept test will detect HPV types 16 and 18, the two types responsible for 70% of cervical

cancer, and we estimate will cost 90%

of cervical cancer. Collectively, this research will lead to the development and implementation of a scalable, cost-

effective screening test, a critical and necessary step toward the global elimination of cervical cancer.