CancerQuest | Cancer Prevention: Cervical Cancer Vaccines

Because of exciting recent developments in this field, we will cover this treatment in more depth than some others and will discuss the development of the treatment

The majority of cervical cancer is believed to be caused by the Human Papillomavirus (HPV). There are more than 100 variants (subtypes) of HPV but only a small subset are associated with human cancer. HPV subtypes 16 and 18 are the variants most commonly associated with human cervical cancer. Several characteristics of HPV make it a good target for vaccine development. The virus is simple, small, and has a stable genome. HPV vaccine development and clinical trials are currently underway.

The Strategy

As discussed in the previous pages, the goal of vaccines is to increase the response of the immune system to particular antigens. The idea is that if our immune system 'sees' the protein again, it will respond very strongly. In the case of viruses, the immune system often reacts to the proteins on the outside of the virus particle.

In a laboratory, it is possible to construct non-infectious virus-like particles (VLPs) that are similar to the infectious virus but are free of viral DNA and can therefore not reproduce. These VLPs contain viral proteins and are capable of generating the same natural humoral immune response following injection into the body. Two different VLP-based Human Papilloma Virus vaccines are at advanced stages of development/usage.

The Agent: Gardasil®
The first preventative cancer vaccine to receive FDA approval was Gardasil®. Gardasil® was designed to prevent infection by four different subtypes of HPV (6, 11, 16, and 18). HPV types 6 and 11 together, cause 90% of the cases of genital warts while 16 and 18 combined, are responsible for 70% of cervical cancer cases. Gardasil® contains VLPs containing the capsid protein of each of these four strains of HPV.

Gardasil® is produced by Merck Pharmaceuticals. The agent was approved by the FDA on June 8, 2006 for the prevention of cervical cancer (and genital warts) in females 9-26 years old and is being tested for its effectiveness in other age groups and in combination with other vaccines. On October 16th,2009 Gardasil® was approved for use in boys and men 9-26 years of age.

More on Gardasil® from Merck
Search for clinical trials involving Gardasil® at the NCI

The Data
Following positive phase I and II clinical trials, a total of 12,167 women, aged 16-26 years, enrolled in a phase III trial at 90 different study centers in Brazil, Colombia, Denmark, Finland, Iceland, Mexico, Norway, Peru, Poland, Singapore, Sweden, the United Kingdom and the United States. Of the more than 12,000 participants, 6,082 females received a three dose regimen of Gardasil while the remaining 6,075 received a placebo. The study evaluated the occurrence of HPV 16/18 associated cervical pre-cancers and non-invasive cancers.

Specifically, participants were screened for moderate (2) and high (3) grade cervical intraepithelial neoplasia (CIN), Grade 3 CIN is also known as carcinoma in situ (CIS). CIS is an immediate precursor to invasive squamous cell cervical cancer. Participants were also examined for the occurrence of AIS adenocarcinoma in situ (AIS), a precursor to glandular cervical cancer. The results of the trial showed that Gardasil® prevented 100 percent of high-grade pre-cancer and non-invasive cancers associated with HPV 16/18. Gardasil® was also found to reduce the risk of developing high-grade pre-cancer and non-invasive cancer in women who may have violated the protocol or become infected with the virus during the time of the trial. The treatment received FDA approval in the summer of 2006.⁽¹⁾ ⁽²⁾ ⁽³⁾ ⁽⁴⁾

Cancer Prevention: Cervical Cancer Vaccines - Gardasil®