Reflections Regarding Validation of New HPV Tests With Reduced HPV Genotypes: Report From an IARC Expert Consultation

Abstract

Of the 12 HPV genotypes classified as carcinogenic to humans (Group 1), over 95% of HPV-positive cervical cancers are linked to eight genotypes (HPV16/18/31/33/35/45/52/58). Screening programmes may consider HPV tests incorporating only these genotypes to improve screening efficiency and reduce programmatic costs. Validation of such tests requires fine-tuning of existing criteria. An expert group convened by the International Agency for Research on Cancer discussed how existing criteria by Meijer et al. for HPV screening clinical validation should be adapted to evaluate new reduced-valency HPV tests. Experts identified four key criteria: (1) Clinical performance criteria should meet WHO HPV test Target Product Profiles (TPP) minimal standards with high relative sensitivity ( ≥ 0.90 for CIN2+ and ≥ 0.95 for CIN3+) and relative specificity ( ≥ 0.98 for ≤ CIN1) to detect CIN2/3+ lesions associated with types targeted by the test, as established by a comparator test providing information on the presence of the targeted genotypes; (2) Comparator tests should be clinically validated according to Meijer criteria principles for comparator tests, and should offer HPV genotyping to detect at least the types included in the reduced-valency test; (3) Cervical samples should be representative of a population-based screening programme; (4) Intra- and inter-laboratory reproducibility should adhere to Meijer criteria and, preferentially also the more stringent TPP. As the global HPV type distribution in cervical cancer is well known, a future evaluation strategy may consider including both virological and simplified clinical standards. The consultation highlights essential criteria building on existing clinical accuracy standards, enriched with analytical standards. These criteria will be instrumental in ensuring both accuracy and reliability of new reduced-valency HPV tests for cervical cancer screening highly needed to assure 70% coverage aim of cervical cancer elimination.