Multi-omics characterization of silent and productive HPV integration in cervical cancer

Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV...

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Veröffentlicht in:Cell genomics 2023-01, Vol.3 (1), p.100211, Article 100211
Hauptverfasser: Fan, Junpeng, Fu, Yu, Peng, Wenju, Li, Xiong, Shen, Yuanming, Guo, Ensong, Lu, Funian, Zhou, Shengtao, Liu, Si, Yang, Bin, Qin, Xu, Hu, Dianxing, Xiao, Rourou, Li, Xi, Yang, Siqi, Yuan, Cunzhong, Shu, Yao, Huang, He, Wan, Ting, Pi, Yanan, Wang, Shuxiang, Chen, Wenjuan, Wang, Haixia, Zhong, Lin, Yuan, Li, Wen, Baogang, Kong, Beihua, Mills, Gordon B., Zou, Dongling, Xia, Bairong, Song, Kun, Chen, Gang, Ma, Ding, Sun, Chaoyang
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Sprache:eng
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Zusammenfassung:Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV integration sites were nonrandomly distributed across both viral and host genomes, suggesting that productive integration sites are under selection and likely to contribute to CC pathophysiology. Furthermore, using large-scale, multi-omics (clinical, genomic, transcriptional, proteomic, phosphoproteomic, and single-cell) data, we demonstrate that tumors with productive HPV integration are associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion. Importantly, productive HPV integration increases from carcinoma in situ to advanced disease. This study improves our understanding of the functional consequences of HPV fusion transcripts on the biology and pathophysiology of HPV-driven CCs, suggesting that productive HPV integration should be evaluated as an indicator of high risk for progression to aggressive cancers. [Display omitted] •HPV integration in cervical cancer shows silent or productive integration status•Productive HPV integration is under selection and likely contributes to CC pathophysiology•Productive HPV integration associates with tumor aggressiveness and immunoevasion Using multi-omics and single-cell data, Fan et al. comprehensively demonstrate the characteristics of silent and productive HPV integration in a large-scale cervical cancer cohort. They reveal that productive HPV integrations are under selection and associated with enhanced tumor aggressiveness, immunoevasion, and tumor progression. The multidimensional integrative analyses deepen our knowledge of HPV integration and have the potential to inform patient management.
ISSN:2666-979X
2666-979X
DOI:10.1016/j.xgen.2022.100211