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High-risk human papillomavirus (hrHPV) DNA is the double-stranded circular genome of oncogenic HPV genotypes, most notably HPV 16 and 18, which are responsible for the vast majority of cervical cancers and a significant proportion of other mucosal malignancies (National Cancer Institute, 2023; World Health Organization, 2022). The viral DNA functions as the template for the expression of E6 and E7 oncoproteins, which facilitate cellular transformation by degrading host tumor suppressors p53 and pRb (UniProt, 2024; PubMed, PMID: 24191933). In the clinical setting, hrHPV DNA is the primary analyte for molecular diagnostic assays, serving as a critical biomarker for cervical cancer screening and risk stratification (FDA, 2021). While prophylactic vaccines target the L1 capsid protein to prevent infection, therapeutic strategies targeting the viral DNA itself—such as CRISPR/Cas9-mediated genome editing—are currently under investigation to treat persistent infections and prevent progression to invasive carcinoma (PubMed, PMID: 30635473). These DNA-directed approaches aim to achieve "molecular surgery" by specifically cleaving viral sequences, thereby inducing apoptosis in infected cells or reverting the transformed phenotype (PubMed, PMID: 28810337).
Inhibition of viral DNA polymerase and site-specific cleavage of viral genomic sequences
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