High-risk human papillomavirus DNA (hrHPV DNA)

High-risk human papillomavirus (hrHPV) DNA is the genetic material of oncogenic HPV genotypes, such as HPV-16 and HPV-18, which are the primary drivers of cervical and other anogenital cancers [1, 14]. The hrHPV genome is a circular, double-stranded DNA molecule of approximately 8 kb that encodes early proteins (E1-E7) for replication and transformation, and late proteins (L1-L2) for viral assembly [9, 15]. Persistent infection with these high-risk types can lead to the integration of viral DNA into the host cell's genome, a hallmark of HPV-induced carcinogenesis [6, 18]. This integration often results in the loss of the E2 regulatory gene and the subsequent overexpression of the E6 and E7 oncoproteins [1, 6]. E6 and E7 promote malignancy by targeting and degrading the host tumor suppressors p53 and pRb, respectively, leading to uncontrolled cell division and genomic instability [3, 14]. Therapeutic strategies targeting hrHPV DNA include prophylactic vaccines that induce antibodies against the L1 capsid protein to prevent infection [12]. Additionally, experimental approaches such as CRISPR/Cas9 gene editing are being developed to directly disrupt viral DNA sequences in infected cells [6, 9]. Other treatments include small molecule inhibitors like cidofovir that interfere with viral DNA replication and therapeutic vaccines designed to stimulate a T-cell response against cells expressing viral antigens [2, 4]. Monitoring hrHPV DNA levels and integration status serves as a critical biomarker for cancer screening and assessing treatment efficacy [15, 16].

Other names

hrHPV DNAOncogenic HPV DNAHigh-risk HPV genomeHPV-16 DNAHPV-18 DNAHPV-31 DNAHPV-33 DNAHPV-45 DNAHPV-52 DNAHPV-58 DNA

Mechanisms include the induction of neutralizing antibodies against the L1 capsid protein to prevent viral entry [12, 18]; inhibition of viral DNA replication by targeting viral or host polymerases and helicases [4, 8]; stimulation of the host immune system via TLR7 agonists or therapeutic vaccines to eliminate infected cells [2, 7]; and experimental gene-editing approaches to directly cleave and disrupt viral DNA sequences [6, 9].