Integration of High-risk Human Papillomavirus into Cellular Cancer-related Genes in Head and Neck Cancer Cell Lines

Overview

Journal Head Neck

Specialties General Surgery
Oncology

Date 2017 Feb 26

PMID 28236344

Citations 22

Authors

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

Affiliations

Soon will be listed here.

Abstract

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. © 2017 Wiley Periodicals, Inc. Head Neck 39: 840-852, 2017.

Citing Articles

Targeted inhibition of BET proteins in HPV16-positive head and neck squamous cell carcinoma reveals heterogeneous transcriptional responses.

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The role of HR-HPV integration in the progression of premalignant lesions into different cancer types.

Catalan-Castorena O, Garibay-Cerdenares O, Illades-Aguiar B, Rodriguez-Ruiz H, Zubillaga-Guerrero M, Leyva-Vazquez M Heliyon. 2024; 10(15):e34999.

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Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review.

King R, Bilger A, Rademacher J, Lambert P, Thibeault S Laryngoscope. 2023; 133(12):3256-3268.

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Function of TRPC1 in modulating hepatocellular carcinoma progression.

Qi H, Wu F, Wang H Med Oncol. 2023; 40(3):97.

PMID: 36797544 DOI: 10.1007/s12032-023-01964-4.

p63 Directs Subtype-Specific Gene Expression in HPV+ Head and Neck Squamous Cell Carcinoma.

Glathar A, Oyelakin A, Gluck C, Bard J, Sinha S Front Oncol. 2022; 12:879054.

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