Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer: Results from the CLEAR HPV study

Objectives: The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay (AHPV-GT) is a qualitative E6/E7 oncogene messenger RNA test that detects HPV 16 and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study was the pivotal, prospective, multicenter US clinical study to validate the Aptima HPV (AHPV) assays. Methods: In this analysis, we evaluated the clinical performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and grade 3 (CIN3) or adenocarcinoma in situ in 912 women with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV) positives as determined by the AHPV assay. Results: Overall, the percent positive for hrHPV was 38.8% (354/912), of which 34.2% (121/354) were GT positive. Among hrHPV-positive women, the risks of CIN2+ were 37.0% for HPV 16 positives, 15.9% for HPV 18/45 positives, 14.3% for other hrHPV positives, and 2.2% for AHPV negatives. The risks of CIN3+ were 20.5% for HPV 16 positives, 9.1% for HPV 18/45 positives, 4.3% for other hrHPV positives, and 0.7% for HPV negatives. Conclusions: We demonstrated that AHPV-GT is a reliable and effective test for cervical cancer risk stratification in women with an ASC-US cytology diagnosis.