Chapter 9: Clinical applications of HPV testing: A summary of meta-analyses
Introduction
The recognition of the strong causal relationship between persistent infection of the genital tract with high-risk HPV types and occurrence of cervical cancer [1] has resulted in the development of a series of HPV-DNA or -RNA detection systems. Detection of high-risk HPV-DNA is considered to be potentially useful in three clinical applications: first as a primary screening test, solely or in combination with a Pap smear to detect cervical cancer precursors; further as a triage test to select women showing minor cytological lesions in their Pap smears needing referral for diagnosis and treatment and, finally, as a follow-up test for women treated for high-grade intraepithelial lesion with local ablative or excisional therapy to predict cure or failure of treatment.
In this chapter, we will summarise and update recently conducted meta-analyses and systematic reviews which synthesise current knowledge on the performance of HPV-DNA testing in each of these three clinical applications.
Section snippets
Triage of cases with minor cytological abnormalities
A first meta-analysis [2], [3] addressed the cross-sectional accuracy of HPV-DNA testing to triage women with an index smear showing atypical squamous cells of unspecified significance (ASCUS) or atypical glandular cells of unspecified significance (AGUS) where the purpose is to detect cervical intraepithelial neoplasia of grade II or worse (CIN-2+) confirmed by histology. Studies were included if the HC2 assay (cocktail of probes for 13 high-risk HPV types) was applied to women with a prior
Absolute accuracy
We retrieved 20 studies, where the accuracy of HC2 for triage of women with findings of ASCUS could be assessed (see Table 1, a1–a20). On average, in 9.7% (95% CI: 7.7–11.7%) and 4.3% (95% CI: 2.7–5.9%) of cases, underlying CIN-2+ or CIN-3+ was found (Table 2). The variation of the accuracy of HC2 triage in detecting these high-grade CIN is displayed in the forest plots in Fig. 1. Overall, HC2 had a sensitivity of 92.5% (95% CI: 90.1–94.9%) and 95.6% (95% CI: 92.8–98.4%) for detecting
Discussion
From this updated review, we can conclude that for the detection of underlying high-grade CIN, virological testing is more sensitive than the cytological examination of a Pap smear, in whatever clinical application. However, the absolute and relative specificity clearly differs from one application to the other. The studies we have pooled had essentially a cross-sectional design. To translate this pooled knowledge into clinical recommendations, we must take into account the natural history of
Disclosed potential conflicts of interest
MA: Travel Grants (GlaxoSmithKline)
PS: Research Grants (Digene Corporation, Roche)
CJLM: Consultant (Digene Corporation, GlaxoSmithKline)
JD: Consultant (Merck and Co., Inc., Sanofi-Pasteur MSD)
Acknowledgements
We received financial support from (1) the European Commission (Directorate of SANCO), Luxembourg, Grand-Duché du Luxembourg, through the European Cancer Network; (2) the DWTC/SSTC (Federal Services for Scientific, Cultural and Technical Affairs of the Federal Government, Belgium) and (3) the Gynaecological Cancer Cochrane Review Collaboration (Bath, UK). We are grateful to Bernadette Claus and Ine Vanmarsenille (of the Scientific Institute of Public Health, Brussels, Belgium) for their
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