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Broad-Range Papillomavirus Transcriptome as a Biomarker of Papillomavirus-Associated Cervical High-Grade Cytology

Abstract : Human Papillomaviruses (HPV) are responsible for over 99% of cervical cancers. Molecular diagnostic tests based on the detection of viral DNA or RNA have low Positive Predictive Values (PPV) for the identification of cancer or precancerous lesions. Triage with the Papanicolaou test lacks sensitivity and even when combined with molecular detection of high-risk HPV results in a significant number of unnecessary colposcopies. We have developed a broad range detection test of HPV transcripts to take a snapshot of the transcriptome of 16 high-risk or putative high-risk HPV in cervical lesions (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82). The purpose of this novel molecular assay is to detect and type HPV-positive samples and to determine a combination of HPV reads at certain specific viral spliced junctions that can better correlate with high-grade cytology, reflecting the presence of precancerous cells. In a proof-of-concept study conducted on 55 patients, starting from cervical smears, we have shown that (i) HPV RNA-Seq can detect papillomaviruses with performances comparable to a widely used HPV reference molecular diagnostic kit, and (ii) a combination of the number of sequencing reads at specific early vs late HPV transcripts can be used as a marker of high-grade cytology, with encouraging diagnostic performances as a triage test.
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Contributor : Philippe Pérot Connect in order to contact the contributor
Submitted on : Wednesday, May 20, 2020 - 10:55:13 AM
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Philippe Pérot, Anne Biton, Jacques Marchetta, Anne-Gaelle Pourcelot, André Nazac, et al.. Broad-Range Papillomavirus Transcriptome as a Biomarker of Papillomavirus-Associated Cervical High-Grade Cytology. Journal of Molecular Diagnostics, American Society for Investigative Pathology (ASIP), 2019, 21 (5), pp.768-781. ⟨10.1016/j.jmoldx.2019.04.010⟩. ⟨pasteur-02613507⟩



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