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

Abstract

Cervical cancer remains a major global burden largely caused by persistent infection with high risk human papillomavirus (HPV). Biological differences between HPV clade A7 and HPV clade A9 may influence tumor programs and clinical outcomes. To propose pharmacological candidates for repositioning, we applied an expression-based drug repurposing approach using the OCTAD (Open Cancer Therapeutic Discovery) framework. Disease transcriptional signatures were constructed for both HPV clades and compared with drug perturbation profiles to identify compounds showing inverse associations with the tumor related expression patterns, restricting the analysis to Food and Drug Administration (FDA) approved agents. The screening identified 41 and 52 candidates for HPV clade A7 and HPV clade A9, respectively, and stronger transcriptomic reversal was associated with higher drug sensitivity in relevant cell lines. These candidates were enriched for pharmacologic classes such as histone deacetylase inhibitors, estrogen pathway modulators, and statins. Additional enriched categories also emerged, including antimetabolites, protein kinase inhibitors, proteasome inhibitors, antimalarials, and antimicrobial agents, several of which already show experimental activity in cervical cancer models. These findings reveal both shared and clade-associated vulnerabilities in HPV-driven cervical cancer and demonstrate the utility of expression-based repurposing for generating actionable hypotheses. The resulting drug lists provide a concise, biologically grounded resource to guide preclinical validation and rational exploration in cervical cancer HPV positive models.