TY - JOUR
T1 - An integrated isothermal nucleic acid amplification test to detect HPV16 and HPV18 DNA in resource-limited settings
AU - Kundrod, Kathryn A.
AU - Barra, Maria
AU - Wilkinson, Alexis
AU - Smith, Chelsey A.
AU - Natoli, Mary E.
AU - Chang, Megan M.
AU - Coole, Jackson B.
AU - Santhanaraj, Akshaya
AU - Lorenzoni, Cesaltina
AU - Mavume, Celda
AU - Atif, Hira
AU - Montealegre, Jane Richards
AU - Scheurer, Michael E.
AU - Castle, Philip E.
AU - Schmeler, Kathleen M.
AU - Richards-Kortum, Rebecca R.
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved.
PY - 2023
Y1 - 2023
N2 - High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce the need for complex instrumentation. We integrated all test components into a low-cost, manufacturable platform, and performance of the integrated test was evaluated with synthetic samples, provider-collected clinical samples in a high-resource setting in the United States, and self-collected clinical samples in a low-resource setting in Mozambique. We demonstrated a clinically relevant limit of detection of 1000 HPV16 or HPV18 DNA copies per test. The test requires six user steps, yields results in 45 min, and can be performed using a benchtop instrument and minicentrifuge by minimally trained personnel. The projected per-test cost is <$5, and the projected instrumentation cost is <$1000. These results show the feasibility of a sample-to-answer, point-of-care HPV DNA test. With the inclusion of other HPV types, this test has the potential to fill a critical gap for decentralized and globally accessible cervical cancer screening.
AB - High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce the need for complex instrumentation. We integrated all test components into a low-cost, manufacturable platform, and performance of the integrated test was evaluated with synthetic samples, provider-collected clinical samples in a high-resource setting in the United States, and self-collected clinical samples in a low-resource setting in Mozambique. We demonstrated a clinically relevant limit of detection of 1000 HPV16 or HPV18 DNA copies per test. The test requires six user steps, yields results in 45 min, and can be performed using a benchtop instrument and minicentrifuge by minimally trained personnel. The projected per-test cost is <$5, and the projected instrumentation cost is <$1000. These results show the feasibility of a sample-to-answer, point-of-care HPV DNA test. With the inclusion of other HPV types, this test has the potential to fill a critical gap for decentralized and globally accessible cervical cancer screening.
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U2 - 10.1126/scitranslmed.abn4768
DO - 10.1126/scitranslmed.abn4768
M3 - Article
C2 - 37343083
AN - SCOPUS:85163125204
SN - 1946-6234
VL - 15
JO - Science translational medicine
JF - Science translational medicine
IS - 701
M1 - eabn4768
ER -