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HPV Vaccine Adverse Events Worrisome Says Key Investigator (Mescape)

publié en 26 juillet 2008

(26 07 2008)

HPV Vaccine Adverse Events Worrisome Says Key Investigator

Gandey

Medscape Medical News 2008. © 2008 Medscape

July 26, 2008 — Serious neurologic, thromboembolic, and autoimmune complications

have

been reported in patients who received human papillomavirus (HPV) vaccines.

Although

not the norm, experts suggest that the events are grave enough to encourage

caution.

" The side effects that have been reported are real and they cannot be brushed

aside, "

Diane Harper, MD, from the Dartmouth Medical School, in Hanover, New Hampshire,

told

Medscape Oncology. Dr. Harper was a principal investigator of clinical HPV

vaccine trials

for both Merck and GlaxoKline.

News reports of adverse events, teen paralysis, and death have fueled public

concern.

Back-to-school immunization clinics are stocking up on Merck's Gardasil and more

than16 million doses have reportedly already been distributed in the United

States alone.

But many parents are questioning whether their children should be vaccinated.

And many

women are wondering whether they should be vaccinated too.

According to the US Food and Drug Administration (FDA), as of June 30, 2008,

more than

9700 adverse events have been reported since the vaccine was approved 2 years

ago. Of

these, 94% were classified as nonserious events and 6% as severe.

Serious Adverse Events

* Nervous system disorders, such as Guillain-Barré syndrome and headache *

Thromboembolic events * Musculoskeletal and connective tissue problems *

Lymphatic

system disorders * Gastrointestinal problems * General disorders and

administration site

conditions * Immune system problems, including hypersensitivity reactions,

bronchospasm, and urticaria

Most Commonly Reported Events * Fainting * Pain at the injection site * Headache

*

Nausea * Fever

To prevent fainting, which can sometimes cause serious harm and lead to head

injuries,

Dr. Harper recommends that patients receive vaccines on a full stomach and be

seated

when the shots are administered. The FDA recommends that patients remain seated

for up

to 15 minutes after vaccination.

Dr. Harper also suggests that physicians not vaccinate patients with personal or

family

histories of the more serious conditions outlined in recent adverse-event

reports.

" Physicians have a responsibility to communicate risks to patients and if

patients and

families are concerned, it is reasonable to hold off on vaccinating, " Dr. Harper

said.

It is a sentiment that is echoed by others, such as Abby Lippman, PhD, from

McGill

University, in Montreal, Quebec, who is chair of the policy committee at the

Canadian

Women's Health Network. In this month's issue of the Journal of Epidemiology and

Community Health, she expresses concern about public policies that have

seemingly

rushed to embrace HPV vaccination. " Why the hurry, " Dr. Lippman asks. Especially

in

developed countries where there is no epidemic of infection and mortality rates

from

cervical cancer have been in decline.

What is Causing Adverse Events ?

The cause of recent complications remains a mystery and it is difficult to know

whether

they are linked to vaccines. " Nobody knows why we are seeing adverse events, "

Dr. Harper

said.

Members of the antivaccine movement point to a number of potential perils,

including the

presence of aluminum in injections. Like many vaccines, Gardasil contains

aluminum salts.

Each 0.5-mL dose contains approximately 225 & #956;g of aluminum, 9.56 mg of

sodium

chloride, 0.78 mg of L-histidine, 50 & #956;cg of polysorbate 80, 35 & #956;g of

sodium borate, and

water.

" The scientific work to date seems to suggest that aluminum salts in vaccines

are safe, "

Dr. Harper said. But she told Medscape Oncology that she heard that 1 lot of

Gardasil

might have had an accidentally high yeast concentration, and this might be why

there are

problems. " No one knows for sure, " Dr. Harper said.

The manufacturer was not available to comment about product yeast

concentrations, but

directed Medscape Oncology to an online statement responding to questions about

recent

adverse effects. " Merck has analyzed the adverse events reported for Gardasil

relating to

the recent reports of death and paralysis, and based on the data available to

Merck,

believes that no safety issue related to the vaccine has been identified. These

types of

events are events that could also be seen in the general population. "

Haupt, MD, executive director of clinical research at Merck's research

laboratories

added : " We remain confident in the safety profile of Gardasil. "

FDA and CDC Issue Joint Statement Reassuring Clinicians and Patients Responding

to

public concern, the FDA and the Centers for Disease Control and Prevention (CDC)

issued a

joint statement on Tuesday reassuring clinicians and patients about the safety

of Gardasil.

A second vaccine, GlaxoKline's Cervarix, is already available in some

countries, but is

still being assessed by the FDA.

Despite company and regulatory assurances, some clinicians, who are also

parents, say

they are less confident about the safety of the vaccines. After reviewing the

information,

Ratner, MD, a cardiologist with a practice in lin Square, New York,

and his wife,

a rheumatologist, opted to have their 17-year-old daughter vaccinated. It is a

decision

they say they now regret.

Following vaccination, their teenage daughter began showing signs and symptoms

of

autoimmune disease. " She went from being a healthy, active teen running, playing

lacrosse, and participating on swim team to becoming a chronically ill patient, "

Dr. Ratner

said.

" I worry about the kids who may be having problems, are perhaps struggling with

immune

damage, and are feeling generally achy and unwell, but are probably going

unreported and

undiagnosed, " he said. Dr. Ratner has 2 younger daughters and he says he

definitely won't

be encouraging either of them to be vaccinated.

Gynecologist Christiane Northrup, MD, told Medscape Oncology that she won't be

advocating that her daughters be vaccinated either. Dr. Northrup appeared on a

recent

episode of the Oprah Winfrey Show, which has an estimated 20 million viewers per

week,

most of them women. She told viewers that healthcare dollars would be better

invested

elsewhere. Questioning the Safety Dr. Northrup recommended that the money going

toward vaccines and related programs be allocated to general health and wellness

initiatives and proper nutrition. This harkens back to the age-old debate

between Louis

Pasteur and Antoine Beauchamp, Dr. Northrup suggests. For most of his career,

Pasteur

subscribed to germ theory, while Beauchamp backed the more unpopular theory of

biological terrain. The question : Is it the germs themselves that make people

sick or a

weakened state of immunity that allows germs to take root ? " Pasteur was widely

supported, but on his death bed conceded that Beauchamp was right, " Dr. Northrup

said

during an interview. She suggests that this is what experts should be

concentrating on

now. Instead of focusing on germ theory by pouring efforts into HPV vaccines,

she says

more resources should be dedicated to fostering the overall health of the host.

Dr.

Lippman makes a similar argument and points to the capacity of healthy,

immunocompetent women to spontaneously clear up to 90% of HPV infections —

infections, she says, almost everyone will one day acquire — within 1 to 2

years. When

Gardasil was approved in the United States in June 2006, it was hailed as an

important day

for public health and for women's health. Dr. Harper was quoted as saying that

the

vaccine is the biggest advance since the Pap smear. Dr. Harper told Medscape

Oncology

that she still thinks this is the case, but enthusiasm must be tempered with

caution. Dr.

Harper noted that we shouldn't be calling the new immunizations cervical cancer

vaccines.

" Even if everyone was vaccinated, we would still have cervical cancer, " she

said. " I don't

want people to be lulled into thinking this will prevent cancer. If Pap

screening rates

decline, cervical cancer rates will rise, " she emphasized. If Pap Screening

Rates Decline,

Cervical Cancer Rates Will Rise The decline in cervical cancer in developed

countries has

been largely attributed to regular Pap screening — something Dr. Harper believes

has

done a superb job. Women who haven't received an HPV vaccine, and even those who

have, are still encouraged to undergo regular screening. At the 2006 American

Society of

Clinical Oncology annual meeting, delegates were enthusiastic. One presenter

showed a

series of cervical cancer photos and told observers that " these types of

pictures will soon

disappear in clinical oncology. " Unfortunately, that utopian prediction is

unlikely. " Cervical

cancer is not a vaccine-preventable disease, " Dr. Lippman said during an

interview. And in

her recent editorial, she points out that surrogate end points — not cervical

cancer — were

used to measure the efficacy in the clinical trials. " No one would want to wait

to see

cervical cancer develop in participants, " she writes. " But the general failure

to mention that

the precancerous lesions chosen for study are not only potentially removable,

most (those

that are CIN 2) would probably have resolved on their own without any

intervention, is

arguable. " Many Questions Remain As previously reported by Medscape Oncology,

Sharmila Makhija, MD, from the University of Alabama School of Medicine, in

Birmingham,

pointed to other limitations of HPV vaccines. Dr. Makhija is the principal

investigator on

Merck's FUTURE III trial, looking at the vaccine's efficacy in women 24 to 45

years old, and

is a coinvestigator on GlaxoKline's vaccine trials. Dr. Makhija noted that

the bulk of

the work to date has focused on just 2 types of HPV — 16 and 18. She added that,

going

forward, more virulent cancer-causing strains could emerge, making it difficult

to

eliminate disease. And other important questions remain : * How long does the

vaccine

last ? * Will it require a booster ? * Who should be vaccinated and at what age

? " While

vaccine proponents emphasize the many thousands of women who participated in

clinical

trials of the product, they gloss over how few young girls in the 9 to 13 year

age range,

targeted specifically for school-based immunizations, were included, " Dr.

Lippman

argues. She said that only the very short-term immunogenicity and safety, and

not the

efficacy, of Gardasil was studied. " It is a good vaccine, " Dr. Harper said. " We

are simply still

in the early stages of investigation. " The World Health Organization (WHO) has

weighed in

on the vaccines and is recommending that they be considered only 1 component of

any

successful strategy. Immunization will have to be added to the other aspects of

cervical

cancer control, s Ullrich, MD, medical officer at WHO's department of

chronic

diseases and health promotion, said in a news release. " There is no question

that early

detection will continue to be a key element. " Merck is encouraging healthcare

providers

and consumers to report any adverse events associated with Gardasil to the

company and

to the US _Vaccine Adverse Event Reporting System_ (http://www.vaers.hhs.gov/)

at 1-

. J Epidemiol Community Health. 2008 ;62:570-571. _Abstract_

(http://www.ncbi.nlm.nih.gov/sites/e...0Community%20Health.[Jour]%20AND%20570[pa\

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