Dataset Information

Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas.

ABSTRACT: Cervical cancer tumors with undetectable HPV (HPVU) have been underappreciated in clinical decision making. In this study, two independent CC datasets were used to characterize the largest cohort of HPVU tumors to date (HPVU = 35, HPV+ = 430). Genomic and transcriptome tumor profiles and patient survival outcomes were compared between HPV+ and HPVU tumors. In vitro analyses were done to determine efficacy of the selective CDK4/6 inhibitor palbociclib on HPVU cancer cell lines. Patients with HPVU CC tumors had worse progression-free and overall survival outcomes compared to HPV+ patients. TP53, ARID1A, PTEN, ARID5B, CTNNB1, CTCF, and CCND1 were identified as significantly mutated genes (SMGs) enriched in HPVU tumors, with converging functional roles in cell cycle progression. In vitro HPVU, but not HPV+, cancer cell lines with wild type RB1 were sensitive to palbociclib monotherapy. These results indicate that HPVU 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 HPVU CC patients.

SUBMITTER: Ruiz FJ

PROVIDER: S-EPMC8467954 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas.

Ruiz Fiona J FJ Sundaresan Aishwarya A Zhang Jin J Pedamallu Chandra S CS Halle Mari K MK Srinivasasainagendra Vinodh V Zhang Jianqing J Muhammad Naoshad N Stanley Jennifer J Markovina Stephanie S Tiwari Hemant K HK Grigsby Perry W PW Krakstad Camilla C Schwarz Julie K JK Ojesina Akinyemi I AI

Cancers 20210910 18

Cervical cancer tumors with undetectable HPV (HPVU) have been underappreciated in clinical decision making. In this study, two independent CC datasets were used to characterize the largest cohort of HPVU tumors to date (HPVU = 35, HPV+ = 430). Genomic and transcriptome tumor profiles and patient survival outcomes were compared between HPV+ and HPVU tumors. In vitro analyses were done to determine efficacy of the selective CDK4/6 i ...[more]

PMID: 34572780

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Dataset Information

Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas.

Publications

Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas.

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