Defense Medical Research and Development
THE PAP SMEAR CHALLENGE: COMPARING CLINICAL PERFORMANCE OF A NOVEL “MOLECULAR PAP” BASED ON NEXT-GENERATION SEQUENCING TO TRADITIONAL CERVICAL CANCER SCREENING
Posted January 28, 2020
J. Shen-Gunther, MD, PhD, COL, MC, Brooke Army Medical Center
COL J. Shen-Gunther
Human Papillomavirus (HPV) is now recognized as the carcinogen of almost all invasive cervical cancers and a major cause of other human malignancies including oral and anal cancers, totaling approximately 600,000 cases annually worldwide. The Pap smear, regarded as the most successful cancer screening test in the history of medicine, has been in existence for over 70 years. However, due to the lack of Pap smear screening programs in developing countries or other social and economic barriers in developed countries, the rates of new cervical cancer cases and deaths remain high worldwide. To circumvent these challenges, COL Jane Shen-Gunther, developed a molecular diagnostic test coined the Molecular Pap based on four molecular markers (Human Papillomavirus genotype and 3 epigenetic markers), innovative molecular technologies, and predictive analytics (or computerized classification). The Molecular Pap has tremendous practical value: (1) improved accuracy, (2) decreased laboratory costs, and (3) complementarity to home-based self-sampling.
With the support from the CRII award, COL Shen-Gunther continues to compare the diagnostic performance of the Molecular Pap to current cervical cancer screening methods in a head-to-head challenge using ~3,000 Pap smear samples from a military population. The ultimate goal is to translate their current discoveries into a cervical cancer screening test that is user-friendly, convenient, accessible, accurate, and affordable for women around the world.
In 2019, the Molecular Pap was licensed to an industry partner along with a Cooperative Research and Development Agreement (CRADA) to develop and commercialize a Research Use Only (RUO) kit for HPV research scientists worldwide. The next milestone is to develop an U.S. FDA-cleared clinical diagnostic test for women. The CRII award also enabled the development a cloud-based, real-world data science workflow to curate computable laboratory data and implement machine learning with predictive analytics. Such automated, artificial intelligence will accelerate and enhance accuracy to create a better diagnostic test for cancer prevention. The “Automated Molecular Pap” prototype software was made possible via a collaboration with Wolfram Solutions (computational software industry partner).
Looking forward, the methodologies and know-how developed by this project may be extended to other HPV-related cancers such as oropharyngeal and male anogenital cancers. Currently, screening tests for these cancers do not exist and are urgently needed.
Figure 1. The “Molecular Pap” is based on physician or self-sampled Pap smears which undergo laboratory-based DNA extraction, Human Papillomavirus (HPV) genotyping and quantitative DNA methylation of 3 genetic markers (left panel). Cloud-based data storage, bioinformatics and predictive analytics are then performed on the 4 molecular targets (HPV and 3 genetic markers) to classify cellular changes in the Pap smear and guide treatment of identified abnormalities. The ultimate goal is to develop an accurate, automated, low cost Pap smear with easy accessibility to results by women globally.
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Last updated Thursday, May 26, 2022