By Norma Erickson, President of SaneVax Inc.
The first papillomavirus was discovered in the 1930’s by Dr. Richard E. Shope. It was the cottontail rabbit papillomavirus, or the Shope papillomavirus, which occurred in warts that frequently developed into cancerous tumors1. Dr. Shope was able to isolate the virus, inject it into other rabbits and produce similar cancerous tumors, thus providing evidence (an animal model) of cancer in mammals apparently caused by a virus.
Although the viral nature of human warts had been noted as early as 1907, little research was done regarding human papillomavirus (HPV) until the development of DNA sequencing technology in the mid 1970’s. Dr. Harald zur Hausen suspected human papillomavirus may exhibit the same progression (warts to cancer) in people that Shope papillomavirus did in rabbits.
After ten years of searching, Dr. zur Hausen discovered HPV 16 and 18 DNA in human invasive cervical cancers. Using the virus DNA retrieved from cervical cancers, he was able to successfully clone HPV 16 and HPV 18 in 19842.
The successful cloning of HPV 16/18 led to research projects aimed at producing the HPV antigens and finding a way to elicit antibodies to them in animals first, and ultimately humans. Research conducted at the University of Queensland (Australia), Georgetown University, the National Cancer Institute, and the University of Rochester culminated in patents filed between 1991 and 1993 by each organization.
Between 1995 and 1998, various pharmaceutical companies obtained rights, or partial rights to these patents. Much of the intellectual property (IP) patented involved knowledge and techniques that overlapped each other with various pharmaceutical companies having the rights to only part of the technology necessary for them to do anything with it.
The United States patent system works on a first to invent basis rather than a first to file system. A patent interference claim arises when two parties have patented similar information. It is basically a priority contest to determine who has the ultimate right to license the patent to other parties. Six two-way patent interference claims between the four inventors were declared by the U.S. Patent and Trademark Office in 2001.
Not knowing which inventing organization would ultimately win the patent interference battle, many pharmaceutical companies who had purchased partial or exclusive rights from one of the four organizations gave up the battle. Merck and GlaxoSmithKline each ended up with rights to utilize the patented information from different organizations.
Given the uncertainty surrounding the ownership of the patented technology enabling the production of HPV vaccines and the possibility that each could block the other’s production, they decided to enter into a cross-license agreement with each other in February 2005. Their market position was now secured in the United States, Europe, and 32 other countries belonging to the Organization for Economic Co-operation and Development3.
In a 2001 article, titled Vaccines: The Next Step to Cervical Cancer Prevention, Journal of the National Cancer Institute, Mark Schiffman, MD, National Cancer Institute Division of Cancer Epidemiology and Genetics responded to this question:
“Once we know how to use information from human papillomavirus tests to effectively test and treat women for cervical abnormalities, what is next?”
“Vaccines,” said Mark Schiffman, M.D., of the National Cancer Institute’s Division of Cancer Epidemiology and Genetics. “[Cervical cancer] should be a vaccine-preventable cancer.”
Remember at this time, the technology to make HPV vaccines was not useable due to multiple patent interference declarations. Dr. Schiffman was offering to take on the task of marketing a vaccine that could not yet be produced for fear of patent interference claims from multiple sources.
All patent applications filed for the inventions of the HPV vaccine technology are about methodologies used to produce the capsid L1 and L2 proteins for eliciting antibodies for the protection against type-specific HPV infections. There are no claims of using HPV L1 or L2 protein as a vaccine to prevent cancer.
The NCI and FDA knew, or should have known, that in the practice of medicine vaccines are used for the prevention of infectious diseases. To use vaccination to control a virus which may lead to cancer development in order to reduce cancer prevalence in a population is theoretically possible, but only a possibility. It is still a concept that needs to be proven; then proven to be safe and effective.
There has never been a single vaccine that is known to be effective for cancer prevention. But, the vaccine developer and manufacturer also know that if an HPV vaccine can be marketed for cervical cancer prevention with the endorsement of the government agencies (NCI, FDA and CDC) and the medical establishment, then consumers would be willing to pay high price for it. After all, cancer is a life-threatening disease with no known effective treatment.
Regardless of the facts, Dr. Mark Schiffman, a government official, openly offered to take on the task of marketing the HPV vaccines as a cancer vaccine in 2001.
The term “cancer vaccine” has not been defined in medical science, let alone for medical practice.
The FDA took a ‘creative’ step when they approved Gardasil as a “cancer vaccine” without officially classifying it as a vaccine against cervical cancer.
They assigned the Gardasil application for pre-marketing approval (PMA) review to the Vaccines and Related Biological Products Advisory Committee (VRBPAC), who then specifically and on public record, in November 2001 and May 2006 officially allowed the vaccine manufacturer, Merck & Co., Inc., to use “CIN 2/3, AIS, or cervical cancer; i.e. CIN 2/3 or worse by histology- with virology to determine the associated HPV type- as the primary endpoint in the evaluation of a vaccine to prevent cervical cancer.”
In this landmark decision, the words “with virology” are merely a token; a dispensable attachment to the endpoint to justify the assignment of the review task to the VRBPAC committee.
After all, by definition a vaccine is for prevention of an infectious disease caused by a microbe or a virus. Cervical cancer is a disease, but not infectious. HPV is a virus, not a disease. There are well over 100 genotypes of HPV, many of which are associated with cervical cancer.
But in the clinical trials, the HPV found in the trial subjects was never genotyped by an FDA-approved method or a reliable DNA sequencing genotyping. The real primary endpoint was “CIN 2/3, AIS, or cervical cancer.” Since cervical cancer takes several decades to develop, there was not a single case of cancer included in the clinical trial data published. Therefore, in reality the only endpoint adopted for efficacy evaluation was “CIN 2/3, AIS” in the materials submitted to the FDA for approval.
Nevertheless, despite the fact that Gardasil met neither of the two qualifying criteria for FDA fast-track designation, CBER (the Center for Biologics Evaluation and Research) granted the designation anyway in 2002. Merck’s development program for the HPV quadrivalent vaccine for ‘prevention of cervical cancer’ was officially on the fast-track and endorsed by the government as a cancer preventive.
Scientifically speaking, Gardasil is qualified as a genotype-specific vaccine to prevent HPV-16 and HPV-18 infections with almost 100% efficacy as claimed, and is proven to be ineffective for clearing vaccine-relevant HPV genotypes which are already present in the subjects being vaccinated.
If an analytically sensitive and reliable HPV test were available to pre-test the sexually active young women before vaccination, and disqualify those already infected with HPV-16 or HPV-18 as candidates to be vaccinated, the sales volume of Gardasil would be reduced.
If such a reliable test is applied for post-vaccination monitoring, it may reveal the truth that the lack of a pre-vaccination screening for an already existent vaccine-relevant HPV infection by HPV-16, -18, -31 and -45, may lead to a post-vaccination increase in precancerous and cancerous lesions due to exacerbation or progression of a persistent vaccine-relevant HPV infection.
The NCI and FDA do not want to face either scenario. As a result, the NCI and FDA decided not to recommend or approve an analytically sensitive and specific reliable genotyping test for HPV to be used in clinical practice.
The CDC, a sister agency of the NCI and FDA, also published an article, concluding that the most sensitive and reliable method for HPV test is PCR/DNA sequencing, in 2000. Both the FDA (2009) and the NCI (2010) have openly stated that the most reliable genotyping is by PCR/DNA sequencing. Yet they all refuse to make the new technology available to medical consumers.
The only benefit in creating such confusion is to ensure a free-hand marketing of HPV vaccines without an objective scientific tool for monitoring. In the absence of a reliable HPV genotyping method for monitoring, all patients found to have a post-vaccination abnormal Pap cytology result can be easily, casually and arbitrarily labeled as the consequence of persistent infections caused by other “carcinogenic” HPV genotypes not targeted by the vaccine, and thus immediately referred to colposcopic biopsies. Then the truth would remain unknown forever.
The truth is what medical consumers around the world deserve. If pharmaceutical companies make products that are safe, affordable, necessary and effective, consumers will gladly purchase them. There is no need to legislate or mandate the use of products that accomplish their stated purpose.
This is but the tip of the iceberg. For more information please read, “Creating an HPV Industry,” an in-depth analysis of the creation and perpetration of the HPV money-making machine.