Abstract
Since the early 1950s, Papanicolaou ("Pap") cytology screening has dramatically reduced cervical cancer mortality in most high-income settings. Currently, human papillomavirus (hpv) vaccination has the greatest potential to reduce the global burden of cervical cancer and precancerous lesions. However, as the prevalence of precancerous lesions declines, maintaining cytology as the primary screening test in settings with established programs might become less efficient. A reduction in test performance (sensitivity, specificity, and positive predictive value) would lead to an increase in unnecessary colposcopy referrals. Fortunately, hpv dna testing has emerged as a suitable candidate to replace cytology. Compared with the Pap test, hpv testing is less specific but much more sensitive in detecting high-grade precancerous lesions, less prone to human error, and more reproducible across settings. Linkage of hpv vaccination and screening registries could serve the added role of monitoring vaccine efficacy. As a triage test, cytology is expected to perform with sufficient accuracy because most hpv-positive smears would contain relevant abnormalities. This approach and others-for example, hpv testing followed by genotyping-are being evaluated in large population studies and have already been recommended in some settings. Other specific biomarkers that might perform well for screening and triage include hpv E6/E7 messenger rna testing, methylation of host or viral genes, and p16(INK4a) staining. Considering the rapid pace of major discoveries and the anticipated arrival of a nonavalent hpv vaccine (currently in phase iii trials), the evidence base in this field has become an elusive target and will continue to be an obstacle for policymakers.
Highlights
In 1941, Georgios Nicholas Papanicolaou first reported that microscopic evaluation of vaginal smears might be a useful approach for detecting uterine cancer[1]
His work eventually led to the establishment of the Pap smear for cervical cancer screening, which is the primary reason that most high-income countries have witnessed a major decline in cervical cancer mortality[2,3,4]
Discovery of hpv as the necessary cause of cervical cancer and subsequent studies to evaluate hpv vaccination and molecular-based screening technologies are among the best examples of multi- and interdisciplinary research on cancer causes and prevention
Summary
In 1941, Georgios Nicholas Papanicolaou first reported that microscopic evaluation of vaginal smears might be a useful approach for detecting uterine cancer[1]. His work eventually led to the establishment of the Pap smear for cervical cancer screening, which is the primary reason that most high-income countries have witnessed a major decline in cervical cancer mortality[2,3,4]. We make the argument that hpv testing alone should be adopted as the primary cervical screening test and might serve the added role of monitoring vaccine effectiveness. Both hpv vaccination and hpv dna testing should be viewed as components along the continuum of care for cervical cancer prevention
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