High-risk human papillomaviruses (HPV) are a primary cause of genital and oropharyngeal cancers. Nucleic acid amplification tests (NAATs) are the current standard in the field for robust identification and genotyping of HPV infections. For more simplistic staining, p16 immunohistochemistry is a widely used biomarker assay for HPV detection in these cancers. p16-positivity, however, is not limited to HPV positive tumors and therefore, not a perfect surrogate for HPV. Recently, Northwestern researchers have discovered that R-loops (trimeric RNA: DNA hybrid structures) are increased 50-fold in cells that maintain high-risk HPV genomes. An antibody which binds to these R-loops would readily detect HPV with simple immunologic staining. There is a need for simple and accurate methods to detect HPV positive cells in cancers and precancers of the cervix, anus, and oral cavity. The current p16 protein is used as a surrogate for HPV positivity measured by nucleic acid testing, but it is not highly sensitive, with 20% of patients who have p16-positive tumors testing negative for HPV DNA or RNA. This technology uses a currently available antibody which binds to R-loops and allows for detection of HPV positive cancerous and pre-cancerous cells and lesions with increased specificity. This detection of R-loops using this has been validated in squamous cell cervical carcinomas in vivo.
PUBLICATION
Templeton C. et al. (2023) p53-dependent R-loop formation and pathogenesis. Proceedings of the National Academy of Sciences 120:35
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