HPV Vaccination Is Not Cost-Effective in the Netherlands

Roxanne Nelson

July 02, 2009

July 2, 2009 — Vaccination against the human papillomavirus (HPV) is not cost-effective in the Netherlands, even under favorable assumptions that include lifelong protection against 70% of all cervical cancers, administration to all women regardless of their risk for cervical cancer, and no adverse effects.

According to a report published online July 1 in the Journal of the National Cancer Institute, in order for the HPV vaccine to become cost-effective among Dutch women, the price would have to be considerably reduced, depending on the long-term effectiveness of the vaccine.

Adding HPV vaccination was not cost-effective, even under favorable assumptions. The authors note that with the current price of €118 per vaccine dose, the addition of the HPV vaccination to the current Dutch screening program had a cost-effectiveness ratio of €53,500 per quality-adjusted life-year (QALY) gained. This cost-effectiveness ratio is considerably higher than the cost-effectiveness threshold of €20,000 per QALY gained, they write, which is the acceptability threshold previously established by the Dutch government for the cervical-cancer screening program. In other words, an intervention with a cost-effectiveness ratio of more than €20,000 per QALY gained was not considered acceptable.

In a favorable situation, where only 1 vaccination round of 3 doses is required for complete lifetime protection against HPV type16/18–related cervical cancer, achieving a cost-effectiveness ratio of €20,000 per QALY gained would require pricing the vaccine at approximately €40 per dose, explain the researchers. If an additional booster vaccination is added, the price per initial vaccination must be €33 per dose, and with 4 booster vaccinations, €16 per dose.

Cost Effectiveness Tied to Declining Incidence

As in many industrialized nations, cervical-cancer–associated mortality has dramatically declined in the Netherlands, due to efficient and widespread screening programs. In 2005 it was 1.6 per 100,000 woman-years [World Standardized Rate (WSR)] in the Netherlands, and this rate is lower than the WSR of 2.5 per 100,000 woman-years in the United States for the period 2001–2005 and 1.9 in the United Kingdom in 2005, according to the authors.

A number of analyses have concluded that HPV vaccination should be cost-effective, but this conclusion is primarily dependent on the incidence and mortality rates of cervical cancer. Low incidence and mortality rates might limit the cost-effectiveness of adding HPV vaccination to a screening program, the researchers comment.

The team, led by Inge M.C.M. de Kok, from the department of public health at Erasmus MC University Medical Center, in Rotterdam, the Netherlands, examined the effect of adding HPV vaccination to the current Dutch cervical-cancer screening program..

Using a microsimulation screening analysis (MISCAN) model, the researchers estimated costs and effects of adding HPV vaccination to the current screening protocol in the Netherlands and examined the impact of changes in the price of vaccination, number of booster vaccinations, vaccination attendance rate, vaccination efficacy, cervical-cancer incidence level, and quality-of-life assumptions on the cost-effectiveness of HPV vaccination.

Cost Efficacy Lower Under Less Favorable Assumptions

Under favorable assumptions, the vaccine was not cost-effective. For comparison, the researchers also calculated the cost-effectiveness ratio and threshold price per dose vaccine under much less favorable assumptions; 5 vaccinations (4 boosters after the initial round) during a lifetime in order to maintain protection, 50% attendance rate (assuming that the 10% of the persistent nonattenders for screening, who were assumed to have a 3-fold higher risk for cervical cancer than the attenders, will not attend vaccination), and 50% efficacy of the vaccine for cervical cancer.

Under less favorable conditions, they did not find the vaccine to be cost-effective at any price. When the HPV vaccination was added to the current screening protocol under these less favorable assumptions, it had a cost-effectiveness ratio of €362,100 per QALY gained. Using these parameters, the price per vaccine dose would have to be -€8 to achieve a cost-effectiveness ratio of €20,000 per QALY gained. In other words, they write, even if the price per dose were €0, the vaccine would still not be cost-effective

There were limitations to the analysis, the researchers note. For example, the impact of herd or community immunity was underestimated, and the impact of the vaccine on other types of HPV-related diseases was also not taken into account.

While long-term adverse effects are not yet known and only a small number of adverse events have been reported in women between the ages of 15 to 26 years, most countries intend to vaccinate 12-year-old girls. Both safety and efficacy have not been tested in the age group, the researchers note, and since cervical cancer is a relatively rare disease in the Netherlands, adverse events due to vaccination will also influence the risk/benefit ratio of vaccination. This highlights the importance of future studies that will evaluate adverse effects among vaccinated 12-year-old girls, primarily for safety and also for cost-effectiveness estimates.

“In conclusion, many uncertainties still exist about the effects of HPV vaccination on HPV-related diseases,” the authors write. “Our cost-effectiveness analysis shows that in the Netherlands, a country with low cervical-cancer incidence and mortality, HPV vaccination is not cost-effective.”

GlaxoSmithKline provided funding for the study, to the department of public Health of the Erasmus University Medical Center. The authors made no disclosures.

J Natl Cancer Inst. Published online July 1, 2009.


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