High-risk human papillomavirus genomes and transcripts (HR-HPV)

High-risk human papillomavirus (HR-HPV) genomes and transcripts are the essential genetic drivers of several human malignancies, most notably cervical, anal, and oropharyngeal cancers (NCI, 2023). The HR-HPV genome is typically a circular, double-stranded DNA molecule that persists episomally or integrates into the host genome, where it utilizes host cellular machinery to produce early transcripts such as E6 and E7 (PubMed, PMID: 29113116). These transcripts encode oncoproteins that facilitate malignant transformation by degrading the tumor suppressors p53 and pRb, respectively, leading to uncontrolled cell proliferation and genomic instability (StatPearls, NBK557663). Therapeutic targeting of these nucleic acids involves diverse strategies, including DNA vaccines (e.g., VGX-3100) that prime the immune system to recognize cells expressing viral transcripts, and experimental approaches like siRNA or CRISPR/Cas9 designed to directly degrade or cleave viral mRNA and DNA (PubMed, PMID: 30263129). By eliminating the expression of these viral drivers, these therapies aim to treat persistent infections and prevent the progression of pre-cancerous lesions to invasive carcinoma.

Other names

HR-HPV DNAHR-HPV mRNAOncogenic HPV nucleic acidsHPV E6/E7 transcriptsHigh-risk human papillomavirus genetic material

Therapeutic vaccines (e.g., VGX-3100) induce T-cell mediated immune responses against proteins encoded by the viral transcripts; prophylactic vaccines (e.g., Gardasil 9) prevent the introduction of the viral genome into host cells via L1-neutralization; experimental siRNA and CRISPR/Cas9 therapies directly target and degrade or cleave viral mRNA and DNA sequences (PubMed, PMID: 30263129).