Acquisition of a high risk Human Papillomavirus (hr HPV) infection is a necessary step in the pathogenesis of cervical cancer. Hr HPV detection has a significantly higher sensitivity in the early detection of cervical precancerous lesions than cytology, but a lower specificity. For primary screening tests higher sensitivity is preferential to a higher specificity, since the goal is to prevent as much as possible. The large majority of cervical cancer screening programs in Europe are still cytology based. A switch from cytology based to hr HPV DNA based screening is being implemented in several pilot settings.Since the specificity of hr HPV-testing in primary screening settings is lower compared to cytology, triage of hr HPV positive women before referral to colposcopy is necessary. Triage with cytology, proliferation proteins, detection of methylated DNA regions and viral load slope plot is being investigated.Different subgroups of patients would benefit from different screening programs. Hr HPV based screening is preferential in women aged 30 years and older. In younger women, cytology has a better performance, since the high prevalence of hr HPV infection makes the specificity of HPV-testing even worse. In vaccinated cohorts hr HV-testing is preferred, since lesions are thought to be smaller and more easily missed by cytology. In low resources setting, hr HPV-testing significantly reduces cervical cancer incidence and cancer mortality, in comparison with cytology and visual inspection based screening.
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