The need to change cervical cancer screening in the post–human papillomavirus vaccination era: the interplay between disease prevalence and risk, test characteristics, and efficiency of screening programs

Screening has been instrumental in reducing the global burden of cervical cancer over the past several decades. However, the landscape of prevention and early detection is rapidly evolving, driven by widespread human papillomavirus (HPV) vaccination, advances in molecular diagnostics, and a growing emphasis on personalized medicine, which collectively call for a reassessment of traditional screening paradigms to align with the new risk landscape. In settings with a high prevalence of cervical precancerous lesions, where cytology and HPV testing yield a substantial proportion of true positives, frequent screening intervals are justified. Conversely, in vaccinated populations where the incidence of precancerous lesions is becoming substantially reduced, screening, irrespective of test modality, produces more false positives, leading to unnecessary diagnostic procedures and their consequent reproductive health risks and psychological distress. In HPV-based screening, reduced positive predictive value (PPV) in vaccinated populations reflects the lower oncogenic potential of nonvaccine HPV types that predominate postvaccination. Although these infections are detectable, they are less likely to progress to high-grade precancer or cancer, thereby lowering PPVs. In cytology-based screening, PPV declines for 2 reasons. First, as vaccine-targeted high-risk infections are eliminated, lower-risk infections account for a greater share of cytologic abnormalities. Second, as true precancerous lesions decline, nonspecific cytologic abnormalities, unrelated to HPV, become more prominent, increasing false positives and further reducing PPV. This commentary, drawing on prior work from our group, examines the complex interplay among disease prevalence, individual risk profiles, test performance, and screening program design and argues for a transition toward risk-based screening strategies that reflect changing epidemiological patterns and align with contemporary public health priorities. It further argues for adaptive, evidence-informed policies that incorporate molecular tools such as HPV genotyping and methylation assays to optimize prevention and early detection in the postvaccination era.