HPV as a Molecular Hacker: How the Virus Hijacks Transcription Factors to Trigger Cancer

Human Papillomavirus (HPV), particularly high-risk strains like HPV16 and HPV18, is a leading cause of cervical and other epithelial cancers. While the oncogenic roles of viral proteins E6 and E7 are well established, the broader impact of HPV on host transcriptional regulation remains incompletely understood. This study investigates the hypothesis that conserved HPV genomic motifs may sequester human transcription factors (TFs), contributing to oncogenesis through altered gene regulation. Methods: We conducted a computational analysis of the genomes of high-risk HPV types using MEME-ChIP for de novo motif discovery, followed by Tomtom for identifying matching human TFs. Protein–protein interactions among the predicted TFs were examined using STRING, and biological pathway enrichment was performed with Enrichr. Results: The analysis revealed conserved viral motifs that potentially bind host TFs across several functional families, including FOX, HOX, NFAT, and zinc finger proteins. Key regulators such as SMARCA1, DUX4, and CDX1 were identified as central nodes of HPV-induced disruption. Enriched pathways included Wnt signaling, transcriptional misregulation in cancer, immune evasion, and chromatin remodeling. Conclusions: HPV exerts multifaceted control over host transcriptional and epigenetic networks. This study highlights the utility of in silico approaches in mapping viral–host interactions and identifies potential therapeutic targets in disrupted regulatory networks.