DRH1 - a novel blood-based HPV tumour marker

EBioMedicine. 2020 Jun:56:102804. doi: 10.1016/j.ebiom.2020.102804. Epub 2020 Jun 11.

Abstract

Background: To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay.

Methods: In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies. Analytical specificity was determined using WHO reference-sera for HPV16/18 and 29 pre- and post-immune sera of Gardasil-9-vaccinees. Tumour-tissue was immunochemically stained for HPV-L1-capsidprotein-expression.

Findings: The DRH1-competitive-serological-assay showed a sensitivity of 95% (95% CI, 77.2-99.9%) for HPV16-driven HNSCC, and 90% (95% CI, 55.5-99.7%) for HPV16-induced anal cancer in HIV-positives. Overall diagnostic specificity was 99.46% for men and 99.29% for women ≥ 30 years. After vaccination, antibody level increased from average 364 ng/ml to 37,500 ng/ml. During post-therapy-monitoring, HNSCC patients showing an antibody decrease in the range of 30-100% lived disease free over a period of up to 26 months. The increase of antibodies from 2750 to 12,000 ng/ml mirrored recurrent disease. We can also show that the L1-capsidprotein is expressed in HPV16-DNA positive tumour-tissue.

Interpretation: HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease. As post-treatment biomarker, the assay allows independent post-therapy monitoring as well as early diagnosis of tumour recurrence. An AUC of 0.96 indicates high sensitivity and specificity for early detection of HPV16-induced disease.

Funding: The manufacturer provided assays free of charge.

Keywords: Antibodies; Blood test; HNSCC; HPV16; Screening; Tumour marker.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anus Neoplasms / blood
  • Anus Neoplasms / virology
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Capsid Proteins / metabolism*
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / virology
  • Carrier Proteins / blood*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • HIV Infections / blood
  • HIV Infections / virology
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / virology
  • Human papillomavirus 16 / immunology*
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / virology*
  • Oncogene Proteins, Viral / metabolism*
  • Papillomavirus Infections / immunology*
  • Papillomavirus Vaccines / immunology
  • Prospective Studies
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Capsid Proteins
  • Carrier Proteins
  • Human Papillomavirus Recombinant Vaccine nonavalent
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • TXNIP protein, human
  • L1 protein, Human papillomavirus type 16