Affiliation: | 1. Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia;2. Faculty of Science, University of Malaya, Institute of Biological Sciences, Kuala Lumpur, Malaysia;3. Haematology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia;4. Department of Otorhinolaryngology, Sarawak General Hospital, Ministry of Health Malaysia, Jalan Hospital, Kuching, Sarawak, Malaysia;5. Department of Otorhinolaryngology, Queen Elizabeth Hospital, Ministry of Health Malaysia, Kota Kinabalu, Sabah, Malaysia;6. Department of Otorhinolaryngology, Kuala Lumpur Hospital, Ministry of Health Malaysia, Kuala Lumpur, Malaysia Department of Surgery, Clinical Campus Faculty of Medicine and Health Sciences, University Putra Malaysia at Kuala Lumpur Hospital, Ministry of Health Malaysia, Kuala Lumpur, Malaysia;7. Department of Otorhinolaryngology, Selayang Hospital, Ministry of Health Malaysia, Batu Caves, Selangor, Malaysia;8. Department of Otorhinolaryngology, Pulau Pinang Hospital, Ministry of Health Malaysia, Georgetown, Pulau Pinang, Malaysia;9. Gleneagles Kuala Lumpur Hospital, Kuala Lumpur, Malaysia Sunway Medical Centre, Bandar Sunway, Selangor, Malaysia |
Abstract: | Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein–Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling. |