DRH1 – a novel blood-based HPV tumour marker

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 . 2À99 . 9%) for HPV16-driven HNSCC, and 90% (95% CI, 55 . 5À99 . 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 30À100% 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.

Response to: “Study results and related evidence do not support use of HPV16 L1 DRH1 antibodies as a cancer screening test”

“…We value all comments on our research, and the opportunity to provide further information on our study describing the HPV16-specific tumour marker DRH1 [1] .…”

Plasma extracellular vesicle microRNA‐491‐5p as diagnostic and prognostic marker for head and neck squamous cell carcinoma

“…Recently, HPV16‐L1 DRH1 epitope‐specific serum Abs, rather than lifetime exposure to HPV, were linked to HPV16‐induced malignant disease. Serum DRH1 Abs showed a 95% sensitivity for HPV16‐driven OPSCC, and the diagnostic specificity was 99.46% for men and 95.6% for women 26 . However, this test was limited to patients with HPV‐related HNSCC.…”

“…Serum DRH1 Abs showed a 95% sensitivity for HPV16‐driven OPSCC, and the diagnostic specificity was 99.46% for men and 95.6% for women. 26 However, this test was limited to patients with HPV‐related HNSCC.…”

Relevance of Human Papillomaviruses in Head and Neck Cancer—What Remains in 2021 from a Clinician’s Point of View?

“…The authors concluded that HPV16 E6 antibodies may have potential clinical utility for the diagnosis and/or prognosis of HPV-driven OPSCC. However, Weiland and co-workers [ 60 ] published only recently a study utilizing a novel HPV16-L1 DRH1 epitope-specific antibody applied in a multi-center study analyzing sera from 1486 patients suffering from various HPV-associated diseases. Here, the authors showed a decline in post-treatment antibody levels and concluded that HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced cancer.…”