November 25, 2002

SECOND OPINION

VACCINE MADNESS

The "Breakthrough" Headlines Have Been Running All Week About A New Vaccine For Cervical Cancer - This Is Medical Science And Health Journalism At Its Worst And A Shameful Example Of How Medical Research Is Taking Dangerous Short-Cuts And Badly Misleading The Public

By Nicholas Regush

http://www.redflagsweekly.com/second_opinion/2002_nov25.html

Whenever you see or hear the word "breakthrough" in a medical news report, duck for cover. Chances are someoneís imagination is hard at work.

The latest medical frenzy involved a vaccine aimed at cervical cancer. The study was published in the November 21 issue of The New England Journal of Medicine (NEJM).

The Reuters New Agency provided this lead: "A vaccine against a cervical cancer-causing virus can protect young women from infection - a success researchers hope will eventually allow them to prevent many cases of cervical cancer."

The virus referred to is the human papillomavirus (HPV).

Reuters quoted Dr. Christopher P. Crum of Brigham and Womenís Hospital in Boston as saying: "This is a great study."

Letís move on.

CBSNews.comís headline asked the question: "Major Cancer Breakthrough?" Then the report proceeded to quote researchers in this manner: "Itís really the first time that a vaccine has been shown to prevent directly a pre-cancerous condition and indirectly a cancerous condition." That quote was attributed to Dr. Carol Brown, a gynacologic oncologist at Memorial Sloan Kettering Cancer Center in New York.

Over at the New York Times, at least the headline was more circumspect: "Experimental Vaccine Appears To Prevent Cervical Cancer." The "deck" or the line underneath the main headline might have read this way: "Appearances Can Be Deceiving." However, the Times chose to report: "The vaccine works by making people immune to a sexually transmitted virus [human papillomavirus] that causes many cases of the disease."

The Times quoted Dr. Laura A. Koutsky of the University of Washington in Seattle, the studyís director as saying: "These are tremendous results."

The Chicago Tribune bought the study too. Its lead paragraph referred to the fact that "after decades of failure," scientists showed early success in preventing human papilloma infection, "which is linked to cervical cancer."

Really?

FIRST, SOME BACKGROUND AND A QUESTION RAISED

Cervical cancer, arising in the lining of the cervix, affects about 13,000 women in the U.S. each year. About 4,000 die. Worldwide, a half million get the disease and 225,000 die.

Back in the 1970s, herpes simplex virus (HSV) was proposed as the sexually-transmitted cause of cervical cancer, based mostly on population studies that showed a correlation of the disease with HSV DNA. That approach shifted to HPV in the 1980s, and over the years, population studies set the pace for the now well-accepted view that cervical cancer is strongly related to the transmission of HPV. This is a group of more than 100 viruses, about 30 of which are said to be linked to cervical cancer. Of these 30 or so, HPV-16 is said to be found in 50 per cent of cervical cancers. HPV-18 accounts for another 20 per cent.

In addition to the population studies which link HPV to cervical cancer, there is, for example, research showing that HPV viral DNA can be found integrated in the genetic structure of cervical cancers.

Back in 1992, however, a question was raised about the dominant and increasingly-entrenched theory that HPV causes cervical cancer. It came from Peter Duesberg and Jody Schwartz, molecular biologists at the University of California at Berkeley. Among the various issues they raised about the acceptance of HPV as the cause of cervical cancer was their fundamental concern that there was a lack of consistent HPV DNA sequences and consistent HPV gene expression in tumors that were HPV-positive. They instead suggested that "rare spontaneous or chemically induced chromosome abnormalities which are consistently observed in both HPV and HSV DNA-negative and positive cervical cancers induce cervical cancer."

In short, Duesberg and Schwartz were pointing to the possibility that "carcinogens may be primary inducers of abnormal cell proliferation rather than HPV or HSV." And hereís the key point: "Since proliferating cells [cancer cells dividing wildly] would be more susceptible to infection than resting cells, the viruses would just be indicators rather than causes of abnormal proliferation."

The concept they raised back in 1992 is still relevant today; only science has gone on to assume that causation of cervical cancer has been well-established. Even the National Cancer Institute( NCI) says that "direct" causation has not been demonstrated; however, the NCI and just about everyone else works with the principle that it has been established. Lip service is paid to other possible factors that may be involved in cervical cancer such as

environmental conditions, including smoking. Even dietary factors - particularly low levels of Vitamin A and folate - have been suggested as associated with a risk for cervical cancer.

But once a vaccine to prevent HPV infection is raised as a weapon to prevent cervical cancer, then itís pretty clear that the medical Establishment has gone all the way in accepting a theory. And itís also quite evident in some of the comments listed above that have been made to reporters.

The headline to the accompanying editorial to the study in the NEJM screams out:

"The Beginning of the End for Cervical Cancer?"

This editorial is more or less an ode to the research published.

Not so fast. Why? Because the study is a disgrace.

A WORTHLESS STUDY

When I first reviewed the study, I couldnít believe the NEJM was putting this research on such a high footing - and that includes the embarrassing editorial.

Essentially this is what the study is about: Of 2,392 young women who were entered into the study, 859 were excluded from the final data analysis - some for technical reasons and the vast majority because they were actually found to be infected with HPV-16 before getting the vaccine.

Of 1,533 women who remained, half were given the vaccine and half the placebo shot.

The results were as follows: No one who was vaccinated developed an HPV-16 infection or a precancerous growth. Of those who received the placebo shot, 41 women became infected with HPV-16, and nine of them had precancerous cervical growths.

On the surface, at least interesting for an early study. But those results became the focus of great jubilation.

But Iíll tell you this: It doesnít take a rocket science to see that the studyís methodology is flawed to such a degree that it doesnít even deserve to be published in some throwaway journal. But then again, the NEJM has, of late, become a depository for bad science.

Still, given that the entire world of health journalism seems to have piled on the bravos for this study and just about every vaccine specialist has come out of the woodwork to applaud yet another vaccine effort, I figured that I would seek out someone who has the guts to face up to the bilge that masquerades as science. I therefore got hold of Howard Urnovitz, who is a scientist dealing in molecular issues and a regular contributor to redflagsweekly.com.

His first reply was that "this is a poorly designed study that fits all-too-well into the legacy of medical incompetence called vaccine research."

Here is what Urnovitz had to say, pretty well reaching the same conclusions that I reached upon careful review of this study:

"These investigators initially enrolled 2,392 women to take part in the study. Immediately, 36 % were disqualified primarily because they had detectable HPV markers, according to the studyís authors, who determined HPV-detectability by either antibody or PCR testing. In other words, the study selected for women who showed some sort of robust natural immunity that kept them from expressing the HPV markers.

"Then the study used a cancer detection method which is known to be inaccurate, with a rate of false negative test results that ranges from 1% to 93 %, despite the fact that it is the only test currently available in the United States to screen women for signs of cervical cancer. (A false negative result means that women who have cervical cancer or precancerous tissues are not being identified when they have a Pap smear.) The women in this study are only monitored for HPV infection if they show a positive Pap smear. But since even the CDC recognizes that the Pap test produces a wide range of false negative results, the HPV studyís foundation - the Pap test - is so unreliable that the rest of the study is rendered highly suspect.

"Also, the HPV test is poorly designed. A positive result was defined as any PCR signal that exceeded the background PCR level associated with an HPV-negative sample of human DNA. This is a risky protocol because PCR tests are plagued with false positive reactions (a positive signal that is not a true detection of the target). Since the authors show no data or reference to data on a secondary test that confirms the gene sequence of a positive signal, they cannot conclude that they are measuring HPV."

So here is what the study really amounts to. Again, Iíll defer to Urnovitz because he lays it very cleanly on the line:

"The proper conclusion of this study should be: Administration of this HPV-16 vaccine reduced the incidence of an uncharacterized PCR signal from a poorly defined cohort which was strongly biased toward a natural immunity.

"Finally, press suggestions or those from the authors that young girls will soon be given at vaccine to prevent cervical cancer are ridiculously premature."

As an aside (make of it what you will), given the great new honesty in medicine these days, it was noted in the NEJM that "some co-authors on the study are with Merck Research Laboratories which developed the vaccine and provided the funding."

Nicholas Regush, RFWís editor, writes the daily Health News Analyzer which separates the hype from health news information that may be of value.