Background 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 [
{"type":"clinical-trial","attrs":{"text":"NCT02428842","term_id":"NCT02428842"}}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.Subject terms:
Oncology, Molecular medicine, Biomarkers, Molecular biology 相似文献