Drug Repositioning for HPV Clade-Specific Cervicouterine Cancer Using the OCTAD Pipeline

Cervical cancer remains a major global burden largely driven by persistent infection with high-risk human papillomavirus (HPV). Biological diversity across HPV phylogenetic clades (α-7 and α-9) may shape tumor programs and outcomes. To accelerate therapeutic options, we implemented an expression based, clade informed drug repurposing pipeline using OCTAD. We built disease signatures for HPV-α7 and HPV-α9 tumors, ranked compounds whose drug perturbation profiles inversely correlated with those signatures, and restricted analyses to FDA-approved agents. The screen yielded 41 and 52 candidates for α7 and α9, respectively, enriched for mechanistically coherent classes, including histone-deacetylase inhibitors, estrogen-pathway modulators, and HMG-CoA-reductase inhibitors. Notably, stronger signature inversion was associated with greater in-vitro sensitivity in relevant cell lines. These results support the feasibility of clade informed, transcriptome guided repurposing and nominate a concise, testable set of therapies for HPV-driven cervical cancer. While prospective validation in appropriate experimental models is essential, our findings highlight both shared and lineage-specific vulnerabilities that could guide rational combinations and biomarker driven studies.