There is universal agreement that HPV is required for the development of cervical disease and that HPV-induced disease is associated with a persistent HPV infection. The introduction of organized cervical cytology screening programs has resulted in a marked reduction in cervical cancer morbidity and mortality. Here, the relative insensitivity of cytology to detect disease was offset by the serial nature of the screening paradigm, where disease [resulting from persistent infection(s)] was often detected over several screening rounds. Many countries are now shifting to primary HPV screening using extended screening intervals. As we embark on this transition, the irony is that we seem to be ignoring some basic first principles of cervical cancer screening, namely the ability to monitor persistent HPV infection directly using extended genotyping (beyond HPV 16/18).
Here we argue that extended genotyping information provides a unique and necessary insight into a woman’s risk for developing disease:
1. It enables the physician to detect persistent infections which have a higher disease risk
2. It can guide management decisions, especially in short-term follow up scenarios
3. It enables comprehensive test of cure to be performed on treated women
(not just for HPV 16/18)
4. It can identify non-HPV16/18 types with an increased CIN3 risk (e.g. HPV 31, 33 and 45) versus just recording “other-high-risk” infections, enabling them to be tracked over time
5. It provides critical information for downstream “risk-based colposcopy” follow up
6. It provides important information on vaccinated women with reduced HPV16/18 disease burden
We illustrate these points using data from the BD Onclarity™ PMA and CE Mark trials and examples from recently published literature. We also demonstrate that extended genotyping overcomes one of the primary deficiencies of the 12-other HPV pool screening approach, namely the inability to accurately assess a patient’s CIN3 risk due to masking (when 2 or more HPV types with different absolute risks result in a pooled average risk that is an underestimate of the highest individual genotype risk).
We conclude that extended genotyping permits an expansion of HPV testing to include all elements of risk management: (i) the detection of prevalent CIN3+ disease; (ii) estimating the 3-year risk for future CIN3+; and (iii) permitting unambiguous detection of persistent infections as another indicator of clinical risk.