Researchers Question Wide Use of HPV Vaccines

http://content.nejm.org/cgi/content/short/359/8/821



http://content.nejm.org/cgi/content/full/359/8/861





http://www.nytimes.com/2008/08/21/he...=1&oref=slogin



Researchers Question Wide Use of HPV Vaccines

By ELISABETH ROSENTHAL

Two vaccines against cervical cancer are being widely used without
sufficient evidence about whether they are worth their high cost or even
whether they will effectively stop women from getting the disease, two
articles in this week's New England Journal of Medicine conclude.

Both vaccines target the human papillomavirus, a common sexually transmitted
virus that usually causes no symptoms and is cleared by the immune system,
but which can in very rare cases become chronic and cause cervical cancer.

The two vaccines, Gardasil by Merck Sharp & Dohme and Cervarix by
GlaxoSmithKline, target two strains of the virus that together cause an
estimated 70 percent of cervical cancers. Gardasil also prevents infection
with two other strains that cause some proportion of genital warts. Both
vaccines have become quick best sellers since they were licensed two years
ago in the United States and Europe, given to tens of millions of girls and
women.

"Despite great expectations and promising results of clinical trials, we
still lack sufficient evidence of an effective vaccine against cervical
cancer," Dr. Charlotte J. Haug, editor of The Journal of the Norwegian
Medical Association, wrote in an editorial in Thursday's issue of The New
England Journal. "With so many essential questions still unanswered, there
is good reason to be cautious."

In her article, Dr. Haug points out the vaccines have been studied for a
relatively short period - both were licensed in 2006 and have been studied
in clinical trails for at most six and a half years. Researchers have not
yet demonstrated how long the immunity will last, or whether eliminating
some strains of cancer-causing virus will decrease the body's natural
immunity to other strains.

More to the point, because cervical cancer develops only after years of
chronic infection with HPV, Dr. Haug said there was not yet absolute proof
that protection against these two strains of the virus would ultimately
reduce rates of cervical cancer - although in theory it should do so.

Dr. Richard Haupt, medical director of Merck, called these concerns "very
theoretical," noting that continuing research and monitoring suggested that
immunity would be longlasting and that the vaccine would not lead to
problems with other strains.

He added that cervical cancer was "just the tip of the iceberg" and that HPV
caused a huge amount of expensive and stressful testing in developed nations
that could be avoided with vaccination.

The vaccines, which require three shots for a complete series, cost about
$400 to about $1,000, depending on the country and the fees for doctors'
visits. Unlike older vaccines that save money by preventing costly disease,
these vaccines cost health systems money.

The second paper published this week, a study by Jane J. Kim and Dr. Sue
Goldie of Harvard, looks at the issue of costs and concludes that the
vaccines will be cost effective only if used in certain ways. In particular,
the researchers say the vaccines will be worth the cost only if they prove
to protect girls for a lifetime, and if current methods for screening for
cervical cancer using Pap smears can be safely adjusted to reduce costs
there. Further research is required in both areas.

"I believe the vaccine is a great advance, but we have to implement it
properly to get the benefits, and that hasn't happened," said Dr. Philip
Davies of the European Cervical Cancer Association.

In developed countries, Pap smear screening and treatment have effectively
reduced cervical cancer death rates to very low levels already. There are
3,600 deaths annually from cervical cancer in the United States, 1,000 in
France and 400 in Britain.

Cervical cancer, like skin cancer, can generally be caught at precancerous
or non-invasive stages and treated. Because the vaccine prevents infection
with only some of the cancer-causing strains, Pap smear screening must
continue even in those who are vaccinated.

The Harvard study concluded that giving the vaccine to 12-year-olds would
cost $43,600 for every "quality adjusted year of life" it saved by
preventing a cancer death; that price would often be considered acceptable
by health officials in wealthy countries, experts say.

Dr. Haupt said the study proved that it was best to vaccinate early. "It
underscores the value of vaccinating pre-adolescent girls," since the
vaccine works fully only in girls who have not been exposed to HPV.

But if the vaccine were given to all girls and women up to age 21, the cost
per year of life saved would be far higher - $120,400, the Harvard study
concluded. And if the vaccines prove to require a booster shot, as many
critics believe, that cost rises to $140,000. In such cases it might make
more economic sense to rely on Pap smear screening alone, the researchers
said.



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