Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas.

Cervical cancer tumors with undetectable HPV (HPV) have been underappreciated in clinical decision making. In this study, two independent CC datasets were used to characterize the largest cohort of HPV tumors to date (HPV = 35, HPV = 430). Genomic and transcriptome tumor profiles and patient survival outcomes were compared between HPV and HPV tumors. In vitro analyses were done to determine efficacy of the selective CDK4/6 inhibitor palbociclib on HPV cancer cell lines. Patients with HPV CC tumors had worse progression-free and overall survival outcomes compared to HPV patients. , , , , , , and were identified as significantly mutated genes (SMGs) enriched in HPV tumors, with converging functional roles in cell cycle progression. In vitro HPV, but not HPV, cancer cell lines with wild type were sensitive to palbociclib monotherapy. These results indicate that HPV status can be translated into the clinic as a predictive biomarker of poor patient response to standard of care treatments. We suggest primary cervix tumors be routinely tested for HPV prior to treatment to identify patients who will benefit from more aggressive precision-driven therapy. Our results identify palbociclib as a lead candidate as an alternative treatment strategy for HPV CC patients.