DRH1 - a novel blood-based HPV tumour marker.

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.

Results of a prospective surgical audit of bilateral paediatric cochlear implantation in the UK.

OBJECTIVES: Since being approved in 2009, bilateral simultaneous cochlear implantation (CI) has been the standard treatment for children in the UK who meet the criteria for CI. The aim was to report surgical outcomes of bilateral CI in the UK. METHODS: Between January 2010 and December 2011, 14 UK CI centres collected data prospectively: demographics, aetiology, use of imaging, device type, surgery duration, use of intra-operative electrophysiology, length of stay, and post-operative complications. RESULTS: 1397 CI procedures in 961 CI recipients were included; 436 bilateral simultaneous, 394 bilateral sequential, and 131 unilateral. The majority (85%) were congenitally deaf. The commonest causes of acquired deafness were meningitis and cytomegalovirus infection. The median age for congenitally deaf bilateral simultaneous CI was 2.2 years, mean surgical duration 4.5 hours. 6.3% surgeries were day case procedures. Eight cases (2.0%) of planned bilateral CI had unilateral surgery. The overall major complication rate was 1.6% (0.9% excluding device failures), including explantation due to infection (0.2%), cerebrospinal fluid leak (0.2%), and meningitis (0.1%). There were no permanent facial nerve palsies and no deaths. Sixty-two (6.5%) immediate minor complications included 12 (1.3%) children with significant vestibular impairment. The complication rate was similar following bilateral CI compared to sequential and unilateral CI, and is comparable to other published series. CONCLUSION: This prospective multi-centre audit provides evidence that bilateral paediatric CI is a safe procedure in the UK, thus endorsing its role as a major therapeutic intervention in childhood deafness.