HPV VIS Detail Information

> This page shows VIS [5016831] detail information, including site information (chromosome, GRCh38 location, disease, sample, etc) and literature information.

Site Information

DVID	5016831
Chromosome	chr9
GRCh38 Location	5429919
Disease	Squamous Cell Carcinoma of Head and Neck
Target Gene	PLGRKT

Literature Information

PubMed PMID	35398964
Year	2022 Aug;16(16):3001-3016
Journal	Mol Oncol
Title	Human papilloma virus integration sites and genomic signatures in head and neck squamous cell carcinoma
Author	Mainguen鑼 J, Vacher S, Kamal M, Hamza A, Masliah-Planchon J, Baulande S, Ibadioune S, Borcoman E, Cacheux W, Calugaru V, Courtois L, Crozes C, Deloger M, Girard E, Delord JP, Dubray-Vautrin A, Larbi Ch鑼卹if L, Dupain C, Jeannot E, Klijanienko J, Lameiras S, Lecerf C, Modesto A, Nicolas A, Rouzier R, Saada-Bouzid E, Saintigny P, Sudaka A, Servant N, Le Tourneau C, Bi鐚玞he I.
Evidence	A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture-HPV method followed by next-generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration [episomal (EPI), integrated in a truncated form revealing two HPV-chromosomal junctions colinear (2J-COL) or nonlinear (2J-NL), multiple hybrid junctions clustering in a single chromosomal region (MJ-CL) or scattered over different chromosomal regions (MJ-SC) of the human genome]. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV-human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis.