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100 1 _ |a Hibbert, Julia
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245 _ _ |a Sensitivity and Specificity of Human Papillomavirus (HPV) 16 Early Antigen Serology for HPV-Driven Oropharyngeal Cancer: A Systematic Literature Review and Meta-Analysis.
260 _ _ |a Basel
|c 2021
|b MDPI
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520 _ _ |a Antibodies against HPV16 early proteins have been shown to be promising biomarkers for the identification of HPV-driven oropharyngeal cancer (HPV-OPC) among OPC cases in multiple studies. A systematic literature search was performed to identify original research articles comparing HPV early antigen serology with established reference methods to determine molecular HPV tumor status. Random-effects models were used to calculate summary estimates for sensitivity and specificity of HPV16 E2, E6 and E7 serology for HPV-OPC. Subgroup analyses were performed to explore heterogeneity across studies and describe variables associated with test performance. We identified n = 23 studies meeting all eligibility criteria and included these in the meta-analysis. E6 serology showed the best performance with pooled sensitivity and specificity estimates of 83.1% (95% confidence interval (CI) 72.5-90.2%) and 94.6% (95% CI 89.0-97.4%), respectively, while E2 and E7 serological assays were highly specific (E2: 92.5% (95% CI 79.1-97.6%); E7: 88.5% (95% CI 77.9-94.4%)) but moderately sensitive (E2: 67.8% (95% CI 58.9-75.6%); E7: 67.0% (95% CI 63.2-70.6%)). Subgroup analyses revealed increased pooled sensitivity for bacterially (89.9% (95% CI 84.5-93.6%)) vs. in vitro expressed E6 antigen (55.3% (95% CI 41.0-68.7%)), while both showed high specificity (95.2% (95% CI 93.0-96.7%) and 91.1% (95% CI 46.6-99.2%), respectively). Pooled specificity estimates for HPV16 E2, E6 and E7 serology were significantly lower in studies utilizing HPV DNA PCR as the only molecular reference method compared to those using a combination of any two reference methods (HPV DNA, RNA, in situ hybridization (ISH), p16 immunohistochemistry (IHC)), or histopathological reference methods (ISH or p16 IHC) as stand-alone marker. In conclusion, HPV16 E6 seropositivity is a highly sensitive and specific biomarker for HPV-OPC. However, its performance differs between serological assays and depends on molecular reference methods.
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650 _ 7 |a antibodies
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650 _ 7 |a meta-analysis
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650 _ 7 |a oropharyngeal cancer
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650 _ 7 |a sensitivity
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650 _ 7 |a serology
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650 _ 7 |a specificity
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650 _ 7 |a systematic review
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700 1 _ |a Halec, Gordana
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700 1 _ |a Baaken, Dan
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700 1 _ |a Waterboer, Tim
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700 1 _ |a Brenner, Nicole
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773 _ _ |a 10.3390/cancers13123010
|g Vol. 13, no. 12, p. 3010 -
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|t Cancers
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|y 2021
|x 2072-6694
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Marc 21