Performance Evaluation of the Aptima hrHPV Nucleic Acid Amplification and Papanicolaou Co-Testing in Cervical Cancer Screening

Abstract

Cervical cancer screening is evolving, with guidelines increasingly favoring high-risk human papillomavirus (hrHPV) nucleic acid amplification tests (NAATs) as a primary method. Although hrHPV NAATs offer high sensitivity for HPV-driven cervical cancers, Papanicolaou (Pap) cytology can detect additional gynecologic malignancies, including HPV-independent ones. This study evaluated the Hologic Aptima hrHPV NAAT and Pap co-testing using 61,089 samples from patients aged ≥21 years screened between 2018 and 2023. The cohort was predominantly White (78.4%), with 16.5% Black, 4.1% Asian, and 38.9% Hispanic subjects. Overall percentage agreement (PA) between hrHPV NAAT and Pap was 87.9%, with high negative PA (93.6%) and lower positive PA (52.3%). Excluding atypical squamous/glandular cell abnormalities improved overall and positive PA to 93.0% and 78.3%, respectively. The Aptima hrHPV NAAT showed high sensitivity for high-grade squamous intraepithelial lesions (98.3%) and squamous cell carcinoma (90.0%) but lower sensitivity for low-grade lesions (73.3%), adenocarcinoma (13.3%), and other malignancies (28.6%). Notably, 29 high-grade lesions or malignant cases had abnormal Pap but were hrHPV negative; 24 (82.8%) were histologically confirmed, including endometrial, cervical, ovarian, and fallopian tube carcinomas (mostly non–HPV-related). These findings emphasize cytology's role in detecting malignancies potentially missed by hrHPV testing alone and support co-testing in diverse populations. The Aptima hrHPV NAAT is not approved by the US Food and Drug Administration for primary HPV screening, reinforcing this need.