Assessing the diagnostic value of Xpert HPV
Authors: Siamak Sabour
Journal: The Lancet Global Health (2020)

Human papillomavirus (HPV)-based screen-and-treat is the recommended approach for cervical cancer screening in low-resource settings, but the relatively low specificity of HPV testing, particularly in women living with HIV, leads to overtreatment. In their diagnostic accuracy study, Louise Kuhn and colleagues (February, 2020)1Kuhn L Saidu R Boa R et al.Clinical evaluation of modifications to a human papillomavirus assay to optimise its utility for cervical cancer screening in low-resource settings: a diagnostic accuracy study.Lancet Glob Health. 2020; 8: e296-e304Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar aimed to evaluate whether HPV type restriction and more stringent cycle threshold cutoffs on Xpert HPV optimise performance characteristics of this assay for screen-and-treat. They recruited 1121 women aged 30–65 years, 586 of whom were HIV-negative and 535 HIV-positive. They reported that the sensitivity of detecting cervical intraepithelial neoplasia grade 2 or greater in women who were HIV-negative using manufacturer-defined cycle threshold cutoffs for all channels was 88·7% and specificity was 86·9%. For women who were HIV-positive, sensitivity was 93·6% and specificity 59·9%. Cycle threshold values from channels detecting HPV type 16, HPV types 18 or 45 (or both), and HPV types 31, 33, 35, 52, or 58 (or more than one of these types) were informative to predict cervical intraepithelial neoplasia grade 2 or greater. I congratulate Kuhn and colleagues on their Article and would like to discuss the importance of the diagnostic added value of Xpert HPV. Knowledge of the accuracy estimates (sensitivity and specificity) does not give the full picture regarding the importance of Xpert HPV in clinical practice. This is because all accuracy estimates can be acceptable, yet the diagnostic added value could be negligible.2Szklo M Nieto FJ Epidemiology Beyond the Basics.3rd edn. Jones and Bartlett, New York2014Google Scholar, 3Grobbee DE Hoes AW Clinical Epidemiology: Principles, Methods, and Applications for Clinical Research.2nd edn. Jones and Bartlett, Burlington2014Google Scholar, 4Moons KGM Biesheuvel C Grobbee DE Test research versus diagnostic research.Clin Chem. 2004; 50: 473-476Crossref PubMed Scopus (98) Google Scholar Diagnostic knowledge is not provided by answering the question of "how accurate is this test?" Diagnostic knowledge is the information needed to answer the question "what is the probability of the presence or absence of a specific disease given these test results?" It is crucial to know that many published diagnostic studies are better characterised as test accuracy research than as diagnostic accuracy research. The objective of test research is to assess whether a single diagnostic test (index test) can adequately show the presence or absence of a particular disease. Test research, as in this paper, often deviates from the main principle of clinically relevant diagnostic research in that clinical practice is not followed, mainly because the diagnostic process by definition involves multiple tests that are variable and sequential. More importantly, the clinical evaluation of Xpert HPV was misleading. The focus of Kuhn and colleagues' study was on the probability of measuring positive or negative results of a single test; however, what about the probability of disease presence?4Moons KGM Biesheuvel C Grobbee DE Test research versus diagnostic research.Clin Chem. 2004; 50: 473-476Crossref PubMed Scopus (98) Google Scholar The authors concluded that more stringent cycle threshold cutoffs on selected channels in Xpert HPV improve specificity with only modest losses in sensitivity, making this assay an optimal choice for HPV-based screen-and-treat in settings with a high prevalence of HIV. Their conclusion should be supported by the methodological issues outlined in this Correspondence. Otherwise, mismanagement of the patients being tested could occur. I declare no competing interests. Clinical evaluation of modifications to a human papillomavirus assay to optimise its utility for cervical cancer screening in low-resource settings: a diagnostic accuracy studyMore stringent cycle threshold cutoffs on selected channels in Xpert HPV improve specificity with only modest losses in sensitivity, making this assay an optimal choice for HPV-based screen and treat in settings with a high prevalence of HIV. These modifications can be made from standard output with no need for new engineering. Decision making about performance characteristics of HPV testing can be shifted to programme implementers and cutoffs selected according to resource availability and community preferences. Full-Text PDF Open AccessAssessing the diagnostic value of Xpert HPV – Authors' replyWe thank Siamak Sabour for drawing attention to the importance of the public health relevance of diagnostic accuracy for cervical cancer screening tests. Indeed Dr Sabor is correct in pointing to some reluctance from practitioners to implement human papillomavirus (HPV)-based screen-and-treat, despite the high sensitivity of HPV testing, because of its relatively low specificity, especially in women living with HIV. In our Article,1 Xpert HPV, similar to other HPV tests, has excellent sensitivity, but specificity is suboptimal, particularly in women living with HIV. Full-Text PDF Open Access