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

J Mol Diagn. 2019 Sep;21(5):768-781. doi: 10.1016/j.jmoldx.2019.04.010. Epub 2019 Aug 12.

Abstract

Human papillomaviruses (HPVs) are responsible for >99% of cervical cancers. Molecular diagnostic tests based on the detection of viral DNA or RNA have low positive predictive values 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, this 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 HPVs in cervical lesions (HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82). The purpose of this novel molecular assay, named HPV RNA-Seq, 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 HPV RNA-Seq can detect papillomaviruses with performances comparable to a widely used HPV reference molecular diagnostic kit; and a combination of the number of sequencing reads at specific early versus late HPV transcripts can be used as a marker of high-grade cytology, with encouraging diagnostic performances as a triage test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • DNA, Viral / genetics
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Molecular Diagnostic Techniques / methods*
  • Neoplasm Grading
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / virology
  • Transcriptome*
  • Triage
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears

Substances

  • Biomarkers, Tumor
  • DNA, Viral