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Cervical screening aims to identify women with high‐grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 2‐3 (HSIL/CIN2‐3) or invasive cervical cancer (ICC). Identification of women with severe premalignant lesions or ICC (CIN3+) could ensure their rapid treatment and prevent overtreatment. We investigated high‐risk human papillomavirus (hrHPV) detection with genotyping and methylation of FAM19A4/miR124‐2 for detection of CIN3+ in 538 women attending colposcopy for abnormal cytology. All women had an additional cytology with hrHPV testing (GP5+/6+‐PCR‐EIA+), genotyping (HPV16/18, HPV16/18/31/45), and methylation analysis (FAM19A4/miR124‐2) and at least one biopsy. CIN3+ detection was studied overall and in women, What's new? Reliable triage of women with cervical intraepithelial neoplasia (CIN) is of high priority as not all lesions progress to invasive carcinoma. Here the authors show that combining the methylation status of tumor suppressor genes FAM19A4 and miR124‐2 with genotyping for high‐risk human papillomavirus results in a highly sensitive and moderately specific triage strategy that identifies women with CIN lesions likely to need rapid treatment. The authors recommend clinical evaluation of the strategy in prospective studies.

The clinically validated high-risk human papillomavirus (hrHPV) Hybrid Capture 2 (HC2) and GP5+/6+-PCR assays were analyzed on an Indicating FTA Elute cartridge (FTA cartridge). The FTA cartridge is a solid dry carrier that allows safe transport of cervical samples. FTA cartridge samples were compared with liquid-based samples for hrHPV and high-grade cervical intraepithelial neoplasia (CIN) detection. One cervical sample was collected in a liquid-based medium, and one was applied to the FTA cartridge. DNA was eluted directly from the FTA cartridge by a simple elution step. HC2 and GP5+/6+-PCR assays were performed on both the liquid-based and the FTA-eluted DNA of 88 women. Overall agreement between FTA and liquid-based samples for the presence of hrHPV was 90.9% with GP5+/6+-PCR and 77.3% with HC2. The sensitivity for high-grade CIN of hrHPV testing on the FTA cartridges was 84.6% with GP5+/6+-PCR and only 53.8% with HC2. By comparison, these sensitivities on liquid-based samples were 92.3% and 100% for GP5+/6+-PCR and HC2, respectively. Therefore, the FTA cartridge shows reasonably good overall agreement for hrHPV detection with liquid-based media when using GP5+/6+-PCR but not HC2 testing. Even with GP5+/6+-PCR, the FTA cartridge is not yet capable of detecting all high-grade CIN lesions.