Triage performance of PAX1[m]/JAM3[m] in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China.

OBJECTIVES: In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1[m]/JAM3[m]) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +). METHODS: The triage performance of liquid-based cytology (LBC) and the PAX1[m]/JAM3[m] test for detecting CIN3 + were compared. RESULTS: In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1[m]/JAM3[m] test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1[m]/JAM3[m](+) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837-0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1[m]/JAM3[m](+). Compared with LBC ≥ ASCUS, PAX1[m]/JAM3[m](+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1[m]/JAM3[m](+) were 3.3 (95% CI 2.0-5.9) and 42.6 (27.1-69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1[m]/JAM3[m](+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8-100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7-26.8%). CONCLUSIONS: In non-16/18 hrHPV(+) women, PAX1[m]/JAM3[m] was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1[m]/JAM3[m](+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity.