Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines

Heather M. Walline, Christine M. Goudsmit, Jonathan B. McHugh, Alice L. Tang, John H. Owen, Bin T. Teh, Erin McKean, Thomas W. Glover, Martin P. Graham, Mark E. Prince, Douglas B. Chepeha, Steven B. Chinn, Robert L. Ferris, Susanne M. Gollin, Thomas K. Hoffmann, Henning Bier, Ruud Brakenhoff, Carol R. Bradford, Thomas E. Carey*, The University of Michigan Head and Neck Specialized Program of Research Excellence (SPORE) Program

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines. Methods: E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. Results: All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. Conclusion: HPV integration into cancer-related genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors.

Original languageEnglish
Pages (from-to)840-852
Number of pages13
JournalHead and Neck
Issue number5
Publication statusPublished - 1 May 2017

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