The American Cancer Society has recommended high-risk human papillomavirus (HPV) testing as the primary screening method for cervical cancer since 2020. Up to this point, the transition from Pap test cytology-based screening or co-testing with cytology and HPV testing has been slow and limited. However, more health systems in the United States are in the process of implementing this change. The transition to HPV-based screening requires a triage strategy for positive results. Genotyping to specifically detect HPV types 16 and 18 in conjunction with reflex cytology for the remaining high-risk HPV genotypes has been the recommended method. Testing options including Dual Stain for p16/Ki-67 and extended HPV genotyping are currently being incorporated into treatment algorithms as alternatives. Methylation testing is another promising method extensively investigated around the world. This review, performed by members of the Clinical Practice Committee of the American Society of Cytopathology, examines the rationale behind the switch away from reliance on Pap test cytology in the cervical cancer screening algorithm and the opportunities and problems associated with the most promising alternative approaches. Published studies that give insight into the performance characteristics of these newer tests are reviewed. At the present time, Pap test cytology remains a viable triage option for positive HPV screening results, but alternative tests have significant appeal and should be considered in tandem with the decision to offer primary HPV screening.
Keywords: Cervical cancer; Dual Stain; Extended HPV genotyping; HPV-Based screening; Methylation testing; Papanicolaou test.
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