Biomarker Blood Test Offers Diagnostic Potential for HPV-Related Cancers

HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease, according to results from a multicenter European study published in EBioMedicine.¹

These findings are based on a highly specific diagnostic test that appears to indicate cancer and predict its course from just a pinprick of blood. The newly developed HPV16-L1 DRH1 epitope-specific serological assay detects levels of DRH1 to HPV16.

Importantly, HPV16 is the most carcinogenic of the 206 HPV-subtypes identified thus far and accounts for up to 90% of HPV-induced cancer deaths.

“This is the first time that we have been able to show a link between raised levels of this specific antibody and HPV cancers, indicating the course of disease,” Thomas Weiland, MD, of the division of General Otorhinolaryngology in Austria’s Medical University of Graz, said in a press release.² “This might raise the potential of being able to detect disease recurrence much earlier than current clinical practice.”

This multicenter study was comprised of 1486 patients, including 301 patients with head and neck squamous cell carcinoma (HNSCC), 12 with HIV-positive anal cancer, 80 who were HIV-positive, 29 who were vaccinated with Gardasil-9, and 1064 healthy controls. Participants were tested for human HPV16-L1 DRH1 antibodies using the DRH1-competitive-serological-assay.

Ultimately, the DRH1-competitive-serological-assay demonstrated 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-positive patients. Moreover, overall diagnostic specificity was 99.46% for men and 99.29% for women 30 years or older.

Following HPV vaccination, the observed antibody level increased from an average of 364 ng/ml to 37,500 ng/ml. During post-therapy monitoring, patients with HNSCC showing an antibody decrease in the range of 30% to 100% lived disease free over a period of up to 26 months. Of note, the increase of antibodies from 2750 ng/ml to 12,000 ng/ml mirrored recurrent disease.

In addition, the investigators were also able to show that the L1-capsid protein is expressed in HPV16-DNA positive tumor-tissue.

“While HPV infection does not indicate cancer, scientists have suspected for some time that if antibodies were to develop, there may be a link to cancer,” Ralf Hilfrich, PhD, founder of Abviris and the creator of the DRH1 blood-based HPV tumor marker, said in the release. “Being able to detect that early enough could have a major impact on patient outcomes.”

“The test’s specificity has enabled scientists to show that rising levels of HPV antibodies in blood do reflect malignancy,” Hilfrich added. “The study also indicates that it may prove diagnostically significant, compared to current detection methods, when a biopsy is hard to access, or where the site of the primary cancer is unknown or unidentifiable, such as very early metastasis.”

Overall, these study results provide promising findings, especially when compared to the most effective cancer screening test so far, the Pap-smear, which has significantly reduced the incidence of HPV-induced cervical cancer, even with less impressive key data of about 50% sensitivity and 98% specificity.

References:

1. Weiland T, Eckert A, Tomazic PV, et al. DRH1 – a novel blood-based HPV tumour marker. EBioMedicine. doi: 10.1016/j.ebiom.2020.102804

2. ‘Pinprick’ biomarker blood test offers diagnostic potential in HPV-related cancers Study shows rising antibody levels predict the course of cancer [news release]. Ahrensburg, Germany. Published November 11, 2020. Accessed November 18, 2020. https://www.newswise.com/articles/pinprick-biomarker-blood-test-offers-diagnostic-potential-in-hpv-related-cancers-study-shows-rising-antibody-levels-predict-the-course-of-cancer?sc=dwhr&xy=10019792