In:
British Journal of Cancer, Springer Science and Business Media LLC, Vol. 124, No. 4 ( 2021-02-16), p. 777-785
Abstract:
Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs. Methods Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed. Results Episomal HPV was much less frequent in CC as compared to anal carcinoma ( p 〈 0.0001). We identified 〉 300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63 . HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours ( p = 0.023). Viral integration type was dependent on HPV genotype ( p 〈 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS ( p = 0.011). Conclusions This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2 ; involved in impaired PARP1 activity and chromosome instability.
Type of Medium:
Online Resource
ISSN:
0007-0920
,
1532-1827
DOI:
10.1038/s41416-020-01153-4
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2002452-6
detail.hit.zdb_id:
80075-2
Permalink