Cancer Vaccines (Fact Sheet)

How do cancer preventive vaccines work?

Cancer preventive vaccines target infectious agents that cause or contribute to the development of cancer (8). They are similar to traditional vaccines, which help prevent infectious diseases, such as measles or polio, by protecting the body against infection. Both cancer preventive vaccines and traditional vaccines are based on antigens that are carried by infectious agents and that are relatively easy for the immune system to recognize as foreign.

What cancer preventive vaccines are approved in the United States?

The U.S. Food and Drug Administration (FDA) has approved two vaccines, Gardasil and Cervarix, that protect against infection by the two types of HPV—types 16 and 18—that cause approximately 70 percent of all cases of cervical cancer worldwide. At least 17 other types of HPV are responsible for the remaining 30 percent of cervical cancer cases (9). HPV types 16 and/or 18 also cause some vaginal, vulvar, anal, penile, and oropharyngeal cancers (10).

In addition, Gardasil protects against infection by two additional HPV types, 6 and 11, which are responsible for about 90 percent of all cases of genital warts in males and females but do not cause cervical cancer.

Gardasil, manufactured by Merck & Company, is based on HPV antigens that are proteins. These proteins are used in the laboratory to make four different types of “virus-like particles,” or VLPs, that correspond to HPV types 6, 11, 16, and 18. The four types of VLPs are then combined to make the vaccine. Because Gardasil targets four HPV types, it is called a quadrivalent vaccine (11). In contrast with traditional vaccines, which are often composed of weakened whole microbes, VLPs are not infectious. However, the VLPs in Gardasil are still able to stimulate the production of antibodies against HPV types 6, 11, 16, and 18.

Cervarix, manufactured by GlaxoSmithKline, is a bivalent vaccine. It is composed of VLPs made with proteins from HPV types 16 and 18. In addition, there is some initial evidence that Cervarix provides partial protection against a few additional HPV types that can cause cancer. However, more studies will be needed to understand the magnitude and impact of this effect.

Gardasil is approved for use in females to prevent cervical cancer and some vulvar and vaginal cancers caused by HPV types 16 and 18, and for use in males and females to prevent anal cancer and precancerous anal lesions caused by these HPV types. Gardasil is also approved for use in males and females to prevent genital warts caused by HPV types 6 and 11. The vaccine is approved for these uses in females and males ages 9 to 26. Cervarix is approved for use in females ages 9 to 25 to prevent cervical cancer caused by HPV types 16 and 18.

The FDA has also approved a cancer preventive vaccine that protects against HBV infection. Chronic HBV infection can lead to liver cancer. The original HBV vaccine was approved in 1981, making it the first cancer preventive vaccine to be successfully developed and marketed. Today, most children in the United States are vaccinated against HBV shortly after birth (12).

Have other microbes been associated with cancer?

Many scientists believe that microbes cause or contribute to between 15 percent and 25 percent of all cancers diagnosed worldwide each year, with the percentage being lower in developed than developing countries (4, 8, 13).

The International Agency for Research on Cancer (IARC) has classified several microbes as carcinogenic (causing or contributing to the development of cancer in people), including HPV and HBV (14). These infectious agents—bacteria, viruses, and parasites—and the cancer types with which they are most strongly associated are listed in the table below.

TABLE 1. Agents and Associated Cancers

Infectious Agents	Type of Organism	Associated Cancers
hepatitis B virus (HBV)	virus	hepatocellular carcinoma (a type of liver cancer)
hepatitis C virus (HCV)	virus	hepatocellular carcinoma (a type of liver cancer)
human papillomavirus (HPV) types 16 and 18, as well as other HPV types	virus	cervical cancer; vaginal cancer; vulvar cancer; oropharyngeal cancer (cancers of the base of the tongue, tonsils, or upper throat); anal cancer; penile cancer; squamous cell carcinoma of the skin
Epstein-Barr virus	virus	Burkitt lymphoma; non-Hodgkin lymphoma; Hodgkin lymphoma; nasopharyngeal carcinoma (cancer of the upper part of the throat behind the nose)
Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8)	virus	Kaposi sarcoma
human T-cell lymphotropic virus type 1 (HTLV1)	virus	adult T-cell leukemia/lymphoma
Helicobacter pylori	bacterium	stomach cancer; mucosa-associated lymphoid tissue (MALT) lymphoma
schistosomes (Schistosoma hematobium)	bacterium	bladder cancer
liver flukes (Opisthorchis viverrini)	bacterium	cholangiocarcinoma (a type of liver cancer)

How are cancer treatment vaccines designed to work?

Cancer treatment vaccines are designed to treat cancers that have already developed. They are intended to delay or stop cancer cell growth; to cause tumor shrinkage; to prevent cancer from coming back; or to eliminate cancer cells that have not been killed by other forms of treatment.

Developing effective cancer treatment vaccines requires a detailed understanding of how immune system cells and cancer cells interact. The immune system often does not “see cancer cells as dangerous or foreign, as it generally does with microbes. Therefore, the immune system does not mount a strong attack against the cancer cells.

Several factors may make it difficult for the immune system to target growing cancers for destruction. Most important, cancer cells carry normal self antigens in addition to specific cancer-associated antigens. Furthermore, cancer cells sometimes undergo genetic changes that may lead to the loss of cancer-associated antigens. Finally, cancer cells can produce chemical messages that suppress anticancer immune responses by killer T cells. As a result, even when the immune system recognizes a growing cancer as a threat, the cancer may still escape a strong attack by the immune system (15).

Producing effective treatment vaccines has proven much more difficult and challenging than developing cancer preventive vaccines (16). To be effective, cancer treatment vaccines must achieve two goals. First, like traditional vaccines and cancer preventive vaccines, cancer treatment vaccines must stimulate specific immune responses against the correct target. Second, the immune responses must be powerful enough to overcome the barriers that cancer cells use to protect themselves from attack by B cells and killer T cells. Recent advances in understanding how cancer cells escape recognition and attack by the immune system are now giving researchers the knowledge required to design cancer treatment vaccines that can accomplish both goals (17, 18).