How to evaluate and select cervical screening and triage tests in vaccinated populations

The substantial changes of human papillomavirus (HPV) type distribution and reductions of cervical precancer and cancer incidence in vaccinated populations, which are entering screening programs now, require reassessment of screening and triage approaches to maintain the balance of benefits and harms of cervical cancer screening. The reduction of precancer and cancer in vaccinated populations affects the risk indicated by most screening and triage tests. Among HPV-positive women, the type distribution changes in vaccinated women to less carcinogenic types that are less likely to progress to precancer, and that cause precancers that are less likely to invade. Conversely, HPV vaccines do not affect the natural history of existing HPV infections. Although infections with vaccine-targeted types are rare in vaccinated populations, their risk of precancer and cancer is not reduced. Host biomarkers that are more closely linked to the carcinogenic process are more likely to perform well in vaccinated individuals compared with biomarkers that mostly reflect HPV infections. We summarize data on HPV screening and triage tests, including cytology, dual stain, and methylation tests, either directly evaluated in vaccinated populations or in HPV genotype strata to estimate their performance in vaccinated populations. Combinations of limited or extended genotyping HPV tests with triage biomarkers can provide meaningful risk stratification for both unvaccinated and vaccinated populations.