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Recently, cervical cancer rates elevation has been noted in women aged 20–39 years in regions with a very high human development index (HDI). The onset of cancer elevation rates is observed in the age range of 25–29 years, which should necessitate effective precancer screening in younger age groups, including those <25 years. From 30.066 liquid-based screening tests results ( n  = 30.066), 3849 liquid-based cytology, 1321 high-risk human papillomavirus (HRHPV) and 316 p16/Ki67 performed in women <30 years were selected. Performance characteristics were calculated for three screening models: primary HRHPV with p16/Ki67 triage, primary cytology with reflex HPV and primary cytology alone. Primary HRHPV with p16/Ki67 triage was significantly more sensitive in high-grade squamous intraepithelial lesion quantified with cervical intraepithelial neoplasia grade 2 or worse [HSIL(CIN2+)] detection than cytology with reflex HRHPV and cytology alone (83.3% vs. 70.8%/45.8%) and had significantly higher diagnostic predictive values (PPV:29.4%/21.3%/22.9%; NPV:91.7%/82.9%/82.2%, respectively at CIN2+ threshold). The number of colposcopies per HSIL(CIN2+) detection indices was 3.4, 4.7 and 4.4, respectively. Primary HPV testing in women <30 years with p16/Ki67 triage of HPV-positive cases might be an effective cervical cancer screening strategy for HSIL(CIN2+) detection with superior diagnostic performance when compared with primary cytology-based models. Women <25 years might also benefit from an introduction to a more sensitive screening approach.

Is Primary HPV with Secondary p16/Ki67 Dual-Stain an Alternative HSIL-Risk Detection Strategy in Cervical Cancer Screening for Women under 30 Years?