Comparison of DNA testing strategies in monitoring human papillomavirus infection prevalence through simulation

Carol Y Lin,Ling Li

doi:10.1186/s12879-016-1969-1

Abstract

BackgroundHPV DNA diagnostic tests for epidemiology monitoring (research purpose) or cervical cancer screening (clinical purpose) have often been considered separately. Women with positive Linear Array (LA) polymerase chain reaction (PCR) research test results typically are neither informed nor referred for colposcopy. Recently, a sequential testing by using Hybrid Capture 2 (HC2) HPV clinical test as a triage before genotype by LA has been adopted for monitoring HPV infections. Also, HC2 has been reported as a more feasible screening approach for cervical cancer in low-resource countries. Thus, knowing the performance of testing strategies incorporating HPV clinical test (i.e., HC2-only or using HC2 as a triage before genotype by LA) compared with LA-only testing in measuring HPV prevalence will be informative for public health practice.MethodWe conducted a Monte Carlo simulation study. Data were generated using mathematical algorithms. We designated the reported HPV infection prevalence in the U.S. and Latin America as the “true” underlying type-specific HPV prevalence. Analytical sensitivity of HC2 for detecting 14 high-risk (oncogenic) types was considered to be less than LA. Estimated-to-true prevalence ratios and percentage reductions were calculated.ResultsWhen the “true” HPV prevalence was designated as the reported prevalence in the U.S., with LA genotyping sensitivity and specificity of (0.95, 0.95), estimated-to-true prevalence ratios of 14 high-risk types were 2.132, 1.056, 0.958 for LA-only, HC2-only, and sequential testing, respectively. Estimated-to-true prevalence ratios of two vaccine-associated high-risk types were 2.359 and 1.063 for LA-only and sequential testing, respectively. When designated type-specific prevalence of HPV16 and 18 were reduced by 50 %, using either LA-only or sequential testing, prevalence estimates were reduced by 18 %.ConclusionEstimated-to-true HPV infection prevalence ratios using LA-only testing strategy are generally higher than using HC2-only or using HC2 as a triage before genotype by LA. HPV clinical testing can be incorporated to monitor HPV prevalence or vaccine effectiveness. Caution is needed when comparing apparent prevalence from different testing strategies.

Highlights

Human papillomavirus (HPV) Deoxyribonucleic acid (DNA) diagnostic tests for epidemiology monitoring or cervical cancer screening have often been considered separately
When the “true” HPV prevalence was designated as the reported prevalence in the U.S, with Linear Array (LA) genotyping sensitivity and specificity of (0.95, 0.95), estimated-to-true prevalence ratios of 14 high-risk types were 2.132, 1.056, 0.958 for LA-only, Hybrid Capture 2 (HC2)-only, and sequential testing, respectively
Type-specific prevalence at baseline, in the United States: HPV16 = 0.047; HPV18 = 0.019; HPV31 = 0.022; HPV33 = 0.015; HPV35 = 0.013; HPV39 = 0.022; HPV45 = 0.020; HPV51 = 0.041; HPV52 = 0.036; HPV56 = 0.023; HPV58 = 0.014; HPV59 = 0.030; HPV66 = 0.034; and HPV68 = 0.016; in Latin America: HPV16 = 0.033; HPV18 = 0.012; HPV31 = 0.012; HPV33 = 0.008; HPV35 = 0.007; HPV39 = 0.004; HPV45 = 0.007; HPV51 = 0.005; HPV52 = 0.007; HPV56 = 0.004; HPV58 = 0.001; HPV59 = 0.004; HPV66 = 0.004; and HPV68 = 0.004 Reduced: HPV16 and HPV18 are reduced by 50 % Abbreviations: SD standard deviation, Sen sensitivity, Spe specificity various testing strategies based on the following definition were calculated

Summary

Introduction

HPV DNA diagnostic tests for epidemiology monitoring (research purpose) or cervical cancer screening (clinical purpose) have often been considered separately. HC2 has been reported as a more feasible screening approach for cervical cancer in low-resource countries. Knowing the performance of testing strategies incorporating HPV clinical test (i.e., HC2-only or using HC2 as a triage before genotype by LA) compared with LA-only testing in measuring HPV prevalence will be informative for public health practice. HPVclinical DNA testing has been considered as a more cost- effective and feasible approach [3]. Because cervical cancer outcomes take years to observe, monitoring HPV infections has served as an early indication of vaccine effectiveness [7, 10,11,12,13]. We compare three HPV DNA testing strategies for monitoring HPV infection prevalence

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Conclusion