Monthly Article
The Cure for Cancer?
By
Manish Jain, MD FACOG
Have we reached the Holy Grail of medicine? Have we found the cure for cancer? As far-fetched as that statement may be, we are a lot closer than any of us ever thought. Earlier this year the Food and Drug Administration (FDA) approved a quadrivalent human papilloma virus-like particle vaccine, Gardasil (Merck Vaccines). This vaccination series has the capability to reduce cervical cancer and other anogenital cancers by up to 70%.
2003 worldwide data shows that cervical cancer had a prevalence of 2.3 million women, an annual incidence of 510,000 women, and an annual mortality of 288,000 women. In the United States incidence approaches 11,000 cases per year with a mortality of 4,000 women per year. Cervical cancer is the second most common cause of overall female cancer-related mortality worldwide. Cervical cancer mortality is the second leading cancer cause of death in U.S. women 20-39 years of age.
Epidemiological and tumor data confirm that human papilloma virus (HPV) DNA can be found in virtually all cervical cancers. This evidence points towards cervical cancer being an infectious disease that is transmitted sexually.
HPV is a family of over 100 viruses. Approximately 30-40 types affect anogenital tissues, with 15-20 oncogenic types, and 5-10 genital wart causing types. HPV 16 and 18 account for 70% of all cervical cancers and high-grade pre-invasive lesions. The five next most prevalent oncogenic types account for only an additional 18% of cases. HPV 6 and 11 are responsible for 95% of genital wart disease. The CDC estimates that there are over 20 million men and women currently infected in the U.S. with an estimated 6.2 million infections each year. It is important to note that HPV infection does not guarantee disease. In fact most infections are transient and produce no clinical symptoms, and give immunity to those specific types of HPV. The host immune system resolves the majority of infections through cell-mediated immunity.
Our current prevention methods of abstinence and condom use have poor acceptance. Currently we have focused on early detection with the Pap smear. Unfortunately Pap smears have high false-positive rates and lead to many further, unnecessary interventions. Pap smears also work best when done yearly. Approximately 20% of all U.S. women reported an abnormal Pap smear during their lifetime. The total cost burden of HPV in the U.S. has been estimated to be $3.9 billion, with $3.6 billion being for abnormal Pap smear follow-up and treatment of pre-invasive lesions. A vaccine to prevent infection provides a novel way to prevent disease.
Gardasil (Merck) is a recombinant, quadrivalent, virus like particle (VLP) vaccine. The vaccine protects against HPV 16, 18, 6, and 11. The VLP used is the L1 capsid protein of previously mentioned viral types. There is no viral DNA included in the vaccine thus no infection or disease can occur. The vaccine is a series of three injections given at 1 day, 2 months, and 6 months. Very few complications were noted with the most common being mild injection site reactions. The vaccine was noted to be 100% effective in preventing cervical dysplasia or genital warts. The FUTURE II trial investigated the ability of the vaccine to prevent high-grade cervical dysplasia, adenocarcinoma in situ, and cervical cancer in 12,000 women aged 16-23 years over a four-year follow up period. The vaccine was 100% effective in the per-protocol population, and 97% effective in the intent to treat analysis.
The CDC recommends that females aged 11-12 years be routinely vaccinated. The vaccine works best when given prior to HPV infection, which increases after initiation of sexual intercourse. Furthermore the CDC recommends that girls as young as 9 years receive the vaccine at their physician’s discretion and that females aged 13-26 years also be vaccinated. The series of 3 injection ranges from $360-500. The Vaccines for Children Program (a federal/state program) makes it available to children covered by Medicaid. Most commercial insurances are slowly starting to cover the vaccine. Merck also has a patient assistance program to provide free vaccines to adults in need.
It is important to remember that we currently do not know how long vaccine-induced immunity will last. It is also not known if this vaccine provides any cross immunity to other HPV types. Patients should also be told that it remains imperative that they continue with regular Pap smears since other HPV types may still cause disease. Still this vaccine provides a paradigm shift in the current practice of medicine. We owe it to all of our patients to provide information on obtaining this cancer preventing vaccine.
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