Compared to cytology, HPV testing has the potential to improve the effectiveness by reducing cervical cancer incidence due to improved early detection and treatment but also a higher risk of over-diagnosis and overtreatment of irrelevant lesions. We systematically evaluated benefits and harms of different HPV-based primary cervical cancer screening strategies in the German health care context.
Method:
A previously validated and published Markov model1 for the German health care context was used to analyze the trade-off between benefits and harms of different screening strategies differing by length of screening interval and test algorithms including HPV testing alone or in combination with cytology or with cytological triage for HPV-positive women. We used published German clinical and epidemiological data as well as test accuracy data from international meta-analyses. We used a benefit-harm frontier for reduction in cervical cancer cases (CC) vs. unnecessary treatment (defined as invasive therapy of < CIN 3) to visualize dominated strategies and incremental harm-benefit ratios.
Result:
Overall, HPV-based screening was more effective than cytology alone, with a relative reduction in cervical cancer incidence of 49%-90% compared to 33% - 80% with cytology alone (depending on screening intervals). The incremental gain in effectiveness with HPV screening compared to cytology was higher and incremental increase in harms was lower with extended screening intervals. Out of 18 strategies, 12 were dominated based on the benefit harm-frontier. Compared to annual cytology, which is currently the recommended standard in Germany, biennial HPV screening was similarly effective but reduced unnecessary treatment (depending on test and follow-up algorithm). In contrast, annual HPV primary screening compared to annual cytology alone would result in an incremental harm-benefit ratio of 12 - 117 unnecessary treatments per additional prevented cervical cancer case (depending on screening adherence rate).
Conclusion:
Based on our decision-analytic benefit-harm frontier analyses, HPV-based cervical cancer screening is more effective than cytology alone, but has a higher risk of overtreatment when used in annual screening. In the German health care context, depending on screening adherence rate biennial or triennial HPV screening for women aged 30 yrs and older is similarly or more effective as annual cytology alone, but with significantly reduced unnecessary treatments.
1. Sroczynski et al. Eur J Cancer 2011;47(11):1633-1646.