Clinical Validation of Four Point‐of‐Care High‐Risk HPV Assays, Including Two Reduced‐Valency Assays, for Cervical Cancer Screening in Low‐Resource Settings

Persistent infection with high‐risk human papillomavirus (HR‐HPV) is the necessary cause of cervical cancer, with approximately 95% of cases attributable to eight most carcinogenic HPV types (16/18/31/33/35/45/52/58). Several HPV assays have recently been developed in India for use in cervical cancer screening, including reduced‐valency tests targeting seven/eight oncogenic HPV types. We evaluated the clinical accuracy and reproducibility of four such assays: PathoDetect‐HPV‐14, HPV‐Q (14 types), Truenat‐HR‐HPV‐Plus (8 types), and PathoDetect‐HPV‐7 (7 types). Using the VALGENT framework, 1159 cervical samples from the ESTAMPA study conducted in Argentina and Costa Rica were analysed with the new assays. The samples included 97 cases of CIN2+ (19 CIN2, 72 CIN3, and 6 cancers). Assay performance was compared in a blinded manner with established reference tests (Cobas‐4800 and Allplex‐HPV‐HR) and reduced‐valency comparators. Sensitivity, specificity, agreement, and repeatability were assessed. Truenat‐HR‐HPV‐Plus demonstrated a sensitivity of 80.4% (95% CI: 71.1–87.8) and specificity of 91.5% (95% CI: 89.5–93.2) for CIN2+. It met IARC validation criteria and showed non‐inferior performance to Allplex‐HPV‐HR‐8, with relative sensitivity of 1.03 (95% CI: 0.96–1.09) for CIN2+ and 1.00 (95% CI: 0.96–1.04) for CIN3+, and relative specificity of 0.99 (95% CI: 0.97–1.00) and 0.98 (95% CI: 0.97–1.00), respectively. Repeatability was 93.3% (κ = 0.79). PathoDetect‐HPV‐7 showed lower sensitivity (68.1%) with specificity of 89.0%. HPV‐Q and PathoDetect‐HPV‐14 did not meet validation criteria. This study represents the first formal validation of reduced‐valency HPV assays and demonstrates that Truenat‐HR‐HPV‐Plus provides robust clinical performance with higher specificity than 14‐valent assays, supporting its potential to improve screening efficiency and reduce unnecessary referrals.