Comparison of whole-viral genome sequencing and PCR-based assay for anal HPV detection to inform clinical implementation

To optimize anal cancer screening strategies, we compared two molecular platforms for anal high-risk Human Papillomavirus (HR-HPV) detection: whole-viral genome sequencing (WGS) and Cobas HPV-test-PCR (RC). Anal swabs from participants at high-risk for HPV acquisition were evaluated for cytological abnormalities and HR-HPV prevalence. Compared to WGS, RC had 51 % sensitivity and 98 % specificity for HPV16, 29 % and 92 % for HPV18, and 74 % and 93 % for non-16/18 HR-HPV. In a population with high prevalence of anal HR-HPV, RC had lower sensitivity in the detection of anal HR-HPV but was more robustly associated with abnormal anal cytology compared to WGS. In addition, WGS-based identification of HPV16 sub-lineages demonstrated that the composite A1, A2, A4, and C1 sub-lineages were associated with a higher risk of abnormal cytology compared to other HPV16 sub-lineages. WGS can further delineate the natural history of anal HR-HPV and their sub-lineages in populations at high-risk for HPV acquisition.