A major medical journal has published a couple of articles which question the wisdom of widespread use of Merck & Co’s cervical cancer vaccine Gardasil in terms of both safety and cost-effectiveness.

The first analysis, which looks at the health and economic implications of human papillomavirus vaccination in the USA (where Gardasil is the only approved jab, though GlaxoSmithKline hopes to get the green light there soon for Cervarix), has been authored by Jane Kim and Sue Goldie at the Harvard School of Public Health and published in The New England Journal of Medicine. They argue that on the assumption that the vaccine provided lifelong immunity, the cost-effectiveness ratio of vaccination of 12-year-old girls was $43,600 per quality-adjusted life-year (QALY) gained, as compared with the current screening practice.

However among older females, the cost-effectiveness of Gardasil becomes less and less favourable, they conclude. For example, the cost-effectiveness ratio for extending a temporary catch-up programme for girls to 18 was $97,300 per QALY, while this rises to $120,400 if extending vaccination for women to the age of 21. The cost for extension to 26 was $152,700 per QALY.

Still, Kim and Goldie add that the real impact of HPV vaccination on cervical cancer will not be observable for decades, a point stressed in an accompanying editorial by Charlotte Haug, editor of the Journal of the Norwegian Medical Association, She notes that several strains of HPV can cause cervical cancer, and two vaccines directed against the currently most important oncogenic strains (the HPV-16 and HPV-18 serotypes) represent good news. However, “the bad news is that the overall effect of the vaccines on cervical cancer remains unknown,” she adds.

Dr Haug goes on to note that “despite great expectations and promising results of clinical trials, we still lack sufficient evidence of an effective vaccine against cervical cancer”. She says that the jabs protect against only two strains, yet published reports of trials show an increasing trend of precancerous cervical lesions caused by HPV serotypes other than HPV-16 and HPV-18. Those results were not statistically significant, however, possibly because there were too few clinically relevant endpoints in the observation periods reported.

She acknowledges the pressure on policymakers worldwide to introduce the HPV vaccine but asks how they can make “rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or – in the worst case – do harm”?

While describing the model presented by Kim and Goldie as “well done and ambitious”, Dr Haug says that “their base-case assumptions are quite optimistic”. They presume lifelong protection(no need for a booster dose), “that the vaccine has the same effect on preadolescent girls as on older women, that no replacement with other oncogenic strains of HPV takes place, that vaccinated women continue to attend screening programs, and that natural immunity against HPV is unaffected”.

She concludes by saying that “whether these assumptions are reasonable is exactly what needs to be tested in trials and follow-up studies” and “with so many essential questions still unanswered, there is good reason to be cautious about introducing large-scale vaccination programmes”.

Merck says its own models suggest the cost per QALY of Gardasil is under $50,000 for women up to 26 and that assumes lifelong immunity. However that assumption can not be put to the test as yet given the short time the jab has been on the market, and Merck has been battling of late to address a slowdown in Gardasil sales of late. It has recently started offering doctors free replacement doses if a privately-insured 19- to 26-year-old woman learns that the jab is not covered.