VALGENT: A protocol for clinical validation of human papillomavirus assays

Abstract

Background: Testing for high-risk HPV is more effective in primary cervical cancer screening than the cytological examination of a Pap smear. Separate genotyping may be useful for triage in both HPV-based and cytology-based screening. Only clinically validated tests should be used in clinical practice.

Objectives: VALGENT is a study framework for test comparison and validation of HPV assays in general and HPV genotyping tests in particular according to clinically relevant outcomes and for clinical applications endorsed by scientific evidence.

Study design: VALGENT involves the collation of fresh or archived cervical cell specimen from women attending routine screening supplemented with cytologically abnormal samples. Multiple aliquots of residual material are sent from a central laboratory to participating laboratories for testing with novel HPV assays with limited, extended or full genotyping capacity. Outcomes are derived from screening and pathology registries. Each VALGENT panel includes an assay already validated for screening. A series of accuracy and concordance statistics were generated.

Results: Currently, two VALGENT study rounds, originated from laboratories in Antwerp (Belgium) and Edinburgh (Scotland), were completed. Two new assays (G5+/6+ PCR-LMNX and Xpert HPV) were validated for screening by showing similar accuracy for cervical precancer as the standard comparator test. For two other tests (BD Onclarity, PapilloCheck) validation was confirmed. Inter-test agreement was high although certain type-specific discordances were observed which warrant further analysis.

Conclusion: VALGENT extends current guidelines for high-risk HPV test validation in cervical cancer screening and has produced a large study resource for test comparison. More robust procedures of sample selection and handling and integration with the global WHO reference laboratory network focusing on analytical accuracy, may result in the generation of an international standard and a formalized system for clinical validation of HPV assays and quality control in HPV-based screening.

Keywords: Cervical cancer; Cervical cancer screening; Diagnostic test accuracy; Human papillomavirus; Quality control; Test validation.