LAUSR

BACKGROUND Cervical cancer, a preventable disease associated with human papillomaviruses (HPV), is responsible for significant morbidity and mortality globally. Primary HPV testing is more sensitive in detecting precancerous cervical lesions than cytologic screening and can be conducted using either DNA- or RNA-based assays. With many assays available, screening programs must select the most appropriate for their population, and it is not yet known whether these assays perform equivalently in the long-term, particularly among women who have a negative HPV test result. This study aims to compare the long-term safety after one negative HPV test across both DNA- and RNA-based testing assays. OBJECTIVES We compare the long-term cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher (CIN2+/CIN3+) outcomes of two DNA-based assays: Digene Hybrid Capture 2 High-Risk HPV DNA Test (QIAGEN; Germantown, Maryland) and cobas 4800 HPV Test (Roche; Indianapolis, Indiana), and one messenger RNA-based assay: Aptima HPV Assay (Hologic; San Diego, California, , using data from the HPV FOCAL-DECADE cohort, by first comparing the positive and negative rates between the assays and then investigating the cumulative incidence of CIN2+ and CIN3+ detection over follow-up among participants in FOCAL-DECADE, according to HPV testing assay. STUDY DESIGN The HPV FOr CerviCAL Cancer Trial (HPV FOCAL) was a randomized controlled trial evaluating human papillomavirus testing for primary cervical cancer screening. The HPV FOCAL-DECADE cohort subsequently followed FOCAL participants passively through the British Columbia Cervix Screening Program Database for up to ten years after FOCAL study exit to examine rates of CIN2+/CIN3+. For the present study, eligible participants had baseline HPV negative results from at least one assay and had one or more cytology screens after baseline (N=9,509 for DNA-based and N=3,473 for DNA- versus RNA-based assay comparisons). We constructed cumulative incidence curves and compared hazard ratios for CIN2+/CIN3+ detection according to assay. RESULTS Over ten years of follow-up, the cumulative incidence of CIN2+/CIN3+ did not significantly differ between the DNA-based assays (HR=0.95 (95% CI=0.84-1.06), p=0.35 and 0.82 (95% CI=0.66-1.01), p=0.06 for CIN2+ and CIN3+, respectively) or between the DNA- and RNA-based assays (HR=0.97 (95% CI=0.87-1.06), p=0.48 and 0.94 (95% CI=0.79-1.13), p=0.52 for CIN2+ and CIN3+, respectively). CONCLUSIONS Among participants who were HPV negative at baseline, the long-term risk of CIN2+/CIN3+ did not significantly differ regardless of whether DNA- or RNA-based human papillomavirus testing assays were used. Screening program decision-makers can be confident that for women who test negative for HPV, DNA- and RNA-based assays have similar CIN2+ outcomes over many years.