The Diagnostic Value of Circulating Cell-Free HPV DNA in Plasma from Cervical Cancer Patients

Cells. 2022 Jul 11;11(14):2170. doi: 10.3390/cells11142170.

Abstract

Circulating cell-free HPV DNA (ccfHPV DNA) may serve as a marker for cervical cancer. In this study, we used digital droplet PCR (ddPCR) to detect and quantify ccfHPV DNA in plasma from patients with HPV16- or HPV18-associated cervical cancer. Blood samples from 60 patients diagnosed with cervical cancer (FIGO IA1-IVA) at Aarhus or Odense University Hospital (June 2018 to March 2020) were collected prior to treatment, and patients were subdivided into an early stage (n = 30) and a late-stage subgroup (n = 30) according to disease stage. Furthermore, blood samples from eight women with HPV16- or 18-associated premalignant conditions (CIN3), and 15 healthy controls were collected. ddPCR was used to analyze plasma from all participants. ccfHPV DNA was detected in 19 late-stage patients (63.33%), 3 early stage patients (10.00%), and none of the CIN3 patients or controls. Quantitative evaluation showed significant correlations between ccfHPV DNA level and stage, tumor score, and tumor size. Thus, our results indicate that ccfHPV DNA may not be a useful marker for early detection of cervical cancer. However, for patients with advanced stage cervical cancer, ccfHPV DNA level represents a promising tool to establish tumor burden, making it useful for establishing treatment response and monitoring the disease.

Keywords: HPV; ccfHPV DNA; cervical cancer; circulating cell-free DNA; circulating cell-free HPV DNA; circulating tumor DNA; ctDNA; ddPCR; digital droplet PCR; human papillomavirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell-Free Nucleic Acids*
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Female
  • Human papillomavirus 16 / genetics
  • Humans
  • Papillomaviridae / genetics
  • Papillomavirus Infections* / complications
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Cell-Free Nucleic Acids
  • DNA, Viral

Grants and funding

This research was funded by IMK Almene Fond, grant number 30-206-365; Civilingeniør Frode V. Nyegaard og hustrus fond, grant number 12-06-2018; Fabrikant Einar Willumsens Mindelegat, grant number 6000073; Folketingsmand J. Christensen og hustrus K. Christensens Fond til støtte af forskning i kræft- og AIDS-sygdomme, grant number 21012021; Grosserer A.V. Lykfeldts og Hustrus legat, grant number 27022021; Harboefonden, grant number 19181; Holms Mindelegat, grant number 20006-1902; Inge og Jørgen Larsens mindelegat, grant number 105 37-05; Krista og Viggo Petersens Fond, grant number 6030/67; Søster og Verner Lipperts fond, grant number 13-12-2017; Vissingfonden, grant number 54622; and Aase og Ejnar Danielsens Fond, grant number 10-002130.