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Commentary on: de Kok IM, van Rosmalen J, Dillner J, et al. Primary screening for human papillomavirus compared with cytology screening for cervical cancer in European settings: cost effectiveness analysis based on a Dutch microsimulation model. BMJ 2012;344:e670.
Implications for practice and research
In the absence of vaccination, primary screening using human papillomavirus (HPV) DNA testing for cervical cancer prevention is potentially cost-effective.
Costs associated with HPV testing must be kept low, particularly when background prevalence of HPV in the population is high.
Screening primarily with cytology was preferred when cytology costs were low, despite lower sensitivity and specificity.
For the same number of quality-adjusted life year's (QALY) gained, fewer lifetime HPV tests were required as a primary screening test (five vs eight for cytology); however, cytology remained the cheaper option.
There is ‘no one size fits all’ situation and each country should assess several factors when deciding on cervical cancer screening, including laboratory infrastructure and accessibility to effective treatment.
Establishing country-specific estimates for factors, including background HPV prevalence, achievable screening coverage and intervention costs is a priority.
Cytology-based screening has significantly reduced the incidence of and mortality from cervical cancer in countries that have sustained well-organised programmes. Meta-analyses of the performance of cytology have shown variable performance1 and in the past 15–20 years the value of cytology has been questioned. Methods to improve the quality of cytology screening have included the introduction of liquid based cytology and the addition of molecular tests, particularly testing for high-risk types of HPV DNA.
Using a microsimulation model of HPV and cervical disease (MISCAN), the authors conducted a comprehensive evaluation of over 1500 strategies comparing primary cytology and primary HPV screening, across different scenarios of triage strategies, screening ages and frequencies. The model simulates and tracks the life histories of a population of women (in this analysis, eight million women born from 1939 to 1992, prior to HPV vaccination, based primarily on data collected in the Netherlands). Study outcomes included measures of life expectancy, adjusted for quality of life associated with cervical cancer or screening events and lifetime costs of the intervention. The authors adhered closely to the conventions of health economic evaluation, adopting a societal perspective, discounting future costs and benefits and reporting the impact of influential variables using extensive sensitivity analysis.
Under most scenarios evaluated, primary screening with HPV DNA testing is the preferred option for cervical cancer prevention, particularly if the costs of HPV DNA testing are low and the background prevalence of HPV is less than 5%.When this is not the case, or when cytology costs are low, primary cytology screening is preferred. Important considerations in implementing HPV DNA testing include quality-controlled programmes that take age into account. Frequent screening of young women (less than 30 years old) detects transient, clinically unimportant infections and abnormalities that may lead to unnecessary interventions. The study found that a greater intensity of screening with respect to age range and frequency was optimal when the background risk of cervical cancer was high, there was no previous screening activity, and when cost-effectiveness thresholds (willingness to pay for a QALY) were high.
This study provides a valuable insight into cervical cancer prevention in European countries. Complementary to the findings from clinical trials around the potential superiority of HPV testing in comparison to cytology testing, this study supports the potential value of HPV DNA testing for primary screening. Primary HPV testing is cost-effective provided the cost of HPV testing is low and prevalence of HPV is not too high. The authors used data primarily from the Netherlands which may not represent broader population characteristics. Regardless of the primary screening test used, infrastructure for performing screening needs to be robust with strong health systems, which is not the case in many Eastern European countries. It is well documented that failure to track women with abnormal results, or to refer them for colposcopy or a secondary triage test, performing appropriate treatment and providing post-treatment follow-up are common causes for screening programmes to fail.
Although the authors suggest that HPV DNA testing should be used as a primary screening test in a variety of European countries, they also suggest centralising testing in large laboratories to reduce costs. This adds further complexity to the screening process and may add costs in terms of delayed giving of results and psychological distress among patients waiting for further management. Triaging women with a positive HPV DNA test, particularly with cytology, has been found to be cost effective, particularly as it allows for longer screening intervals for HPV DNA negative women. Cost-effectiveness analyses from a clinical point of view add value in terms of policy formulation. They do not, however, address the complexity of initiating and maintaining cervical cancer screening programmes, even in developed countries with strong healthcare systems. HPV vaccination programmes with high coverage are likely to reduce the need for complex, mass screening programmes in the future.
Competing interests None.
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