RNA-based high-risk HPV genotyping and identification of high-risk HPV transcriptional activity in cervical tissues.
Biomarkers, Tumor
/ genetics
Female
Genotype
High-Throughput Nucleotide Sequencing
Human Papillomavirus DNA Tests
Humans
Papillomaviridae
/ genetics
Papillomavirus Infections
/ diagnosis
Predictive Value of Tests
Proof of Concept Study
Prospective Studies
RNA, Viral
/ genetics
Risk Assessment
Risk Factors
Sequence Analysis, RNA
Specimen Handling
Uterine Cervical Neoplasms
/ diagnosis
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
14
07
2019
accepted:
02
09
2019
revised:
30
08
2019
pubmed:
21
9
2019
medline:
26
1
2021
entrez:
21
9
2019
Statut:
ppublish
Résumé
Nearly all cervical cancers are initiated by a persistent infection with one of the high-risk human papillomaviruses (high-risk HPV). High-risk HPV DNA testing is highly sensitive but cannot distinguish between active, productive infections and dormant infections or merely deposited virus. A solution for this shortcoming may be the detection of transcriptional activity of viral oncogenes instead of mere presence of high-risk HPVs. In this study, fresh-frozen cervical tissues (n = 22) were subjected to high-risk HPV DNA detection using the line probe assay and to targeted RNA next-generation sequencing using single-molecule molecular inversion probes. Targeted RNA sequencing was applied for (1) RNA-based genotyping of high-risk HPV, giving information on specific HPV-subtype (2) discrimination of E2, E6, and E7 transcripts and (3) discovery of possible non-HPV cancer biomarkers. Data were analyzed using computational biology. Targeted RNA sequencing enabled reliable genotyping of high-risk HPV subtypes and allowed quantitative detection of E2, E6, and E7 viral gene expression, thereby discriminating cervical lesions from normal cervical tissues. Moreover, targeted RNA sequencing identified possible cervical cancer biomarkers other than high-risk HPV. Interestingly, targeted RNA sequencing also provided high-quality transcription profiles from cervical scrape samples, even after 1 week of dry storage or storage in Preservcyt fixative. This proof of concept study shows that targeted RNA sequencing can be used for high-risk HPV genotyping and simultaneous detection of high-risk HPV gene activity. Future studies are warranted to investigate the potential of targeted RNA sequencing for risk assessment for the development of cervical lesions, based on molecular analysis of cervical scrapes.
Identifiants
pubmed: 31537894
doi: 10.1038/s41379-019-0369-7
pii: S0893-3952(22)00899-7
doi:
Substances chimiques
Biomarkers, Tumor
0
RNA, Viral
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
748-757Références
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