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Updated: Jul 30, 2025

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Circulating HPV DNA as a Biomarker for Pre-Invasive and Early Invasive Cervical Cancer: A Feasibility Study.

Stacey J Bryan1, Jen Lee2,3, Richard Gunu4

  • 1UCL Elizabeth Garrett Anderson Institute for Women's Health, Faculty of Population Health Sciences, University College London, Medical School Building, 74 Huntley Street, London WC1E 6AU, UK.

Cancers
|May 13, 2023
PubMed
Summary

Circulating HPV-DNA (cHPV-DNA) was not detected in pre-invasive cervical lesions. Detection of cHPV-DNA in early invasive cervical cancer (CC) was very low, suggesting current methods lack sensitivity for clinical use.

Keywords:
cervical cancercirculating DNAhuman papillomavirusliquid biopsynext generation sequencingplasma

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Area of Science:

  • Oncology
  • Virology
  • Molecular Diagnostics

Background:

  • High-risk human papillomavirus (HPV) infection is the primary cause of over 99% of cervical cancers (CC).
  • Persistent HPV infections can lead to cancer, with tumor cells shedding HPV-DNA into the bloodstream (cHPV-DNA).
  • Next-generation sequencing (NGS) assays show high sensitivity for detecting cHPV-DNA in advanced CC.

Purpose of the Study:

  • To investigate the detectability of cHPV-DNA in early invasive cervical cancers.
  • To determine if cHPV-DNA is present in pre-invasive cervical intraepithelial neoplasia (CIN) lesions.

Main Methods:

  • Plasma samples were collected from patients with CIN (n=52) and early-stage CC (FIGO 1A-1B, n=12).
  • Circulating HPV-DNA (cHPV-DNA) was extracted from plasma and detected using NGS.
  • Samples were analyzed pre-treatment and during follow-up.

Main Results:

  • No patients with pre-invasive lesions (CIN) tested positive for cHPV-DNA.
  • Only one patient (10%) with early invasive CC had detectable cHPV-DNA in plasma.
  • Low detection rates were observed even with sensitive NGS technology.

Conclusions:

  • The low detection rate of cHPV-DNA in early CC may be due to small tumor size and limited shedding into circulation.
  • Current NGS-based detection of cHPV-DNA in early invasive cervical cancer lacks sufficient sensitivity for clinical application.
  • Further research is needed to improve diagnostic sensitivity for early-stage cervical cancer detection.