http://www.nytimes.com/2008/08/21/health/21vaccine.html

August 21, 2008

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.