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HPV Integration in HNSCC Correlates with Survival Outcomes, Immune Response Signatures, and Candidate Drivers.
- Source :
-
Molecular cancer research : MCR [Mol Cancer Res] 2018 Jan; Vol. 16 (1), pp. 90-102. Date of Electronic Publication: 2017 Sep 19. - Publication Year :
- 2018
-
Abstract
- The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing deescalated treatment approaches for HPV <superscript>+</superscript> HNSCC patients. RNA sequencing (RNA-seq) data from HNSCC tumors ( n = 84) were used to identify and characterize expressed integration events, which were overrepresented near known head and neck, lung, and urogenital cancer genes. Five genes were recurrent, including CD274 (PD-L1) A significant number of genes detected to have integration events were found to interact with Tp63, ETS, and/or FOX1A. Patients with no detected integration had better survival than integration-positive and HPV <superscript>-</superscript> patients. Furthermore, integration-negative tumors were characterized by strongly heightened signatures for immune cells, including CD4 <superscript>+</superscript> , CD3 <superscript>+</superscript> , regulatory, CD8 <superscript>+</superscript> T cells, NK cells, and B cells, compared with integration-positive tumors. Finally, genes with elevated expression in integration-negative specimens were strongly enriched with immune-related gene ontology terms, while upregulated genes in integration-positive tumors were enriched for keratinization, RNA metabolism, and translation. Implications: These findings demonstrate the clinical relevancy of expressed HPV integration, which is characterized by a change in immune response and/or aberrant expression of the integration-harboring cancer-related genes, and suggest strong natural selection for tumor cells with expressed integration events in key carcinogenic genes. Mol Cancer Res; 16(1); 90-102. ©2017 AACR .<br /> (©2017 American Association for Cancer Research.)
- Subjects :
- Female
Head and Neck Neoplasms immunology
Head and Neck Neoplasms mortality
Humans
Male
Middle Aged
Papillomavirus Infections immunology
Squamous Cell Carcinoma of Head and Neck immunology
Squamous Cell Carcinoma of Head and Neck mortality
Survival Analysis
Treatment Outcome
Head and Neck Neoplasms virology
Papillomaviridae genetics
Papillomavirus Infections virology
Squamous Cell Carcinoma of Head and Neck virology
Virus Integration
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3125
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cancer research : MCR
- Publication Type :
- Academic Journal
- Accession number :
- 28928286
- Full Text :
- https://doi.org/10.1158/1541-7786.MCR-17-0153