Division of STD Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, NE, MS E-63, Atlanta, GA, 30333, USA.
BMC Infect Dis. 2015 Mar 12;15:123. doi: 10.1186/s12879-015-0851-x.
Researchers often group various HPV types into composite measures based on vaccine subtypes, oncogenic potential, or phylogenetic position. Composite prevalence estimates based on PCR genotyping assay results have been calculated to assess HPV infection burden and to monitor HPV vaccine effectiveness. While prevention and intervention strategies can be made based on these prevalence estimates, the discussion on how well these prevalence estimates measure the true underlying infection burdens is limited.
A simulation study was conducted to evaluate accuracy of using composite genotyping assay results to monitor HPV infection burden. Data were generated based on mathematical algorithms with prespecified type-specific infection burdens, assay sensitivity, specificity, and correlations between various HPV types. Estimated-to-true prevalence rate ratios and percent reduction of vaccine types were calculated.
When "true" underlying type-specific infection burdens were prespecified as the reported prevalence in U.S. and genotyping assay with sensitivity and specificity (0.95, 0.95) was used, estimated-to-true infection prevalence ratios were 2.35, 2.29, 2.18, and 1.46, for the composite measures with 2 high-risk vaccine, 4 vaccine, 14 high-risk and 37 HPV types, respectively. Estimated-to-true prevalence ratios increased when prespecified "true" underlying infection burdens or assay specificity declined. When prespecified "true" type-specific infections of HPV 6, 11, 16 and 18 were reduced by 50%, the composite prevalence estimate of 4 vaccine types only decreased by 17% which is much lower than 48% reduction in the prespecified "true" composite prevalence.
Composite prevalence estimates calculated based on panels of genotyping assay results generally over-estimate the "true" underlying infection burdens and could under-estimate vaccine effectiveness. Analytical specificity of genotyping assay is as or more important than analytical sensitivity and should be considered in selecting assay to monitor HPV.
研究人员通常根据疫苗亚型、致癌潜能或系统发育位置将各种 HPV 类型组合成复合措施。基于聚合酶链反应基因分型检测结果计算了复合流行率估计值，以评估 HPV 感染负担并监测 HPV 疫苗的有效性。虽然可以基于这些流行率估计值制定预防和干预策略，但关于这些流行率估计值在多大程度上衡量真实潜在感染负担的讨论有限。
进行了一项模拟研究，以评估使用复合基因分型检测结果监测 HPV 感染负担的准确性。数据是根据具有预设的特定类型感染负担、检测灵敏度、特异性和各种 HPV 类型之间相关性的数学算法生成的。计算了估计与真实流行率比率和疫苗类型的减少百分比。
当“真实”潜在特定类型感染负担被指定为美国报告的流行率，并且使用灵敏度和特异性（0.95，0.95）的基因分型检测时，复合措施的估计与真实感染流行率比率分别为 2.35、2.29、2.18 和 1.46，用于包含 2 种高危型疫苗、4 种疫苗、14 种高危型和 37 种 HPV 类型的复合措施。当预设“真实”潜在感染负担或检测特异性下降时，估计与真实流行率比率增加。当预设 HPV 6、11、16 和 18 的“真实”特定类型感染减少 50%时，4 种疫苗类型的复合流行率估计仅下降 17%，远低于预设“真实”复合流行率的 48%降幅。
基于基因分型检测结果组合而成的复合流行率估计值通常会高估“真实”潜在感染负担，并可能低估疫苗的有效性。基因分型检测的分析特异性与分析灵敏度一样重要或更重要，在选择监测 HPV 的检测方法时应予以考虑。
