Gardasil: More Answers, More Questions
1 CommentBy Ed Silverman // May 9th, 2007 // 6:20 pm
There’s a great deal written about Merck’s Gardasil in this week’s edition of The New England Journal of Medicine - three studies, an essay and two editorials. The studies indicate the vaccine is effective in preventing HPV in uninfected young women for three years, and also prevents lesions that can grow into vaginal and vulvar cancer.
But in one editorial, the Journal’s editors note some limitations. “Although this is a remarkable achievement, the efficacy of the vaccine is limited by at least these two factors. First, not all cervical cancer is caused by HPV-16 or HPV-18 (the two strains Gardasil effectively combats), and second, it appears necessary to vaccinate young women before they are infected with these two serotypes. Also, whether this approach will extend the paradigm of vaccination to the prevention of death and disability from cervical cancer is an unanswered question.”
They follow that up with these questions:
- Should young men be vaccinated?
- How long will protection last?
- Must three shots be needed for adequate protection?
- Will pricing put a vaccine out of reach of developing nations?
- Could a vaccine prevent HPV-induced head and neck cancers?
In another editorial, George Sawaya and Karen Smith-McCune of the department of obstetrics and gynecology at the University of California in San Francisco, wrote that that “investigators in these trials have hit their mark soundly: the vaccine showed significant efficacy against anogenital and cervical lesions…”
But they noted an apparent lack of efficacy among subjects with evidence of previous exposure to HPV types included in the vaccine. And they noted “another factor explaining the modest efficacy of the vaccine is the role of oncogenic HPV types not included in the vaccine…(and) at least 15 oncogenic HPV types have been identified, targeting only two types may not have had a great effect on overall rates of preinvasive lesions.”
“On one hand, the vaccine has high efficacy against certain HPV types that cause life-threatening disease, and it appears to be safe; delaying vaccination may mean that many women will miss an opportunity for long-lasting protection. On the other hand, a cautious approach may be warranted in light of important unanswered questions about overall vaccine effectiveness, duration of protection, and adverse effects that may emerge over time.”
One of the studies;
NEJM editors’ editorial;
Guest editorial.[tags]Cervical Cancer, Gardasil, HPV, Merck[/tags]
mhatrw
To summarize this published medical journal article:
1. In the FUTURE I trial, GARDASIL demonstrated no clinical efficacy among the general subject population for overall reduction in the rates of grade 2 and grade 3 cervical intraepithelial neoplasia and adenocarcinoma — the only recognized precursors to cervical cancer.
2. In the larger FUTURE II trial, GARDASIL demonstrated no clinical efficacy among the general subject population for overall reduction in the rates of grade 3 cervical intraepithelial neoplasia and adenocarcinoma — the strongest (and many would argue only valid) precursors to cervical cancer.
3. Extrapolating from GARDASIL’s very limited clinical “success” (in the FUTURE II study only) against grade 2 cervical dysplasias (40% of which regress spontaneously), 129 women would be have to be vaccinated (at a cost of about $60,000) to prevent a single grade 2 cervical dysplasia.
4. GARDASIL’s protection against cancer associated HPV strains 16 and 18 appears to cause a disproportionate increase in of pre-cancerous dysplasias associated with other HPV strains associated with cervical cancer “raising the possibility that other oncogenic HPV types eventually filled the biologic niche left behind after the elimination of HPV types 16 and 18.”
5. Even if you segregate out the women who hadn’t been previously exposed to either HPV 16 or 18, we are talking about just a 17% decrease in all high grade dysplasias (266 out of 6080 vs. 219 out of 6087) — many of which would spontaneously regress without treatment. So we would have vaccinate 129 women (at about $500 for the three shot regimen) to avoid a single, eminently treatable dysplasia. That’s about $60,000 per dysplasia prevented.
This is all directly from the article linked above.
I myself would add that we currently have only 3 years of follow up to go on in terms of both GARDASIL’s safety and efficacy among the 16 to 26 year female population, no data concerning its efficacy among 9 to 12 year old girls and only 18 months of follow up on less than 600 total preteen girls in terms of safety data about GARDASIL within its targeted population.