Ramírez Arianis Tatiana, Clifford Gary M, Dillner Joakim, Kuhn Louise, Arbyn Marc, Bhatla Neerja, Wentzensen Nicolas, Sasieni Peter, Abraham Priya, Rol Mary Luz, Almonte Maribel, Basu Partha
Early Detection, Prevention & Infections Branch, International Agency for Research on Cancer, Lyon, France.
Department of Clinical Science Intervention & Technology, Center of Cervical Cancer Elimination, Karolinska Institutet, Stockholm, Sweden.
J Med Virol. 2025 Mar;97(3):e70310. doi: 10.1002/jmv.70310.
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.
在被归类为对人类致癌的12种HPV基因型（第1组）中，超过95%的HPV阳性宫颈癌与8种基因型（HPV16/18/31/33/35/45/52/58）有关。筛查计划可考虑采用仅包含这些基因型的HPV检测，以提高筛查效率并降低计划成本。此类检测的验证需要对现有标准进行微调。由国际癌症研究机构召集的一个专家组讨论了Meijer等人用于HPV筛查临床验证的现有标准应如何调整，以评估新的低价HPV检测。专家们确定了四个关键标准：（1）临床性能标准应符合世界卫生组织HPV检测目标产品概况（TPP）的最低标准，具有高相对灵敏度（CIN2+≥0.90，CIN3+≥0.95）和相对特异性（≤CIN1≥0.98），以检测与检测所针对类型相关的CIN2/3+病变，这是通过提供目标基因型存在信息的比较试验确定的；（2）比较试验应根据Meijer比较试验标准原则进行临床验证，并应提供HPV基因分型，以检测至少低价检测中包含的类型；（3）宫颈样本应代表基于人群的筛查计划；（4）实验室内部和实验室间的可重复性应符合Meijer标准，最好也符合更严格的TPP。由于宫颈癌中全球HPV类型分布是已知的，未来的评估策略可考虑纳入病毒学和简化的临床标准。此次磋商强调了在现有临床准确性标准基础上建立的基本标准，并丰富了分析标准。这些标准将有助于确保新的低价HPV检测用于宫颈癌筛查的准确性和可靠性，这对于实现消除宫颈癌70%覆盖率的目标至关重要。
