What to Know About Human Papillomavirus (HPV) Vaccines

Why Only One Is Recommended for Use in the US

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Vaccines for human papillomavirus (HPV) are used to prevent HPV infection and reduce a person's risk of getting HPV-associated cancers in later life, including cervical cancer and anal cancer.

Over the years, there have been several vaccines approved for use by the U.S. Food and Drug Administration (FDA), but, as of May 2017, Gardasil-9 is the only HPV vaccine approved for use by the Centers for Disease Control and Prevention (CDC) that is still on the market.

Closeup of doctor hand are vaccinations to patients using the syringe.Medical concept
Manit Chaidee / Getty Images

While the other two vaccines—the original Gardasil and Cervarix—are still used around the world, both have been voluntarily discontinued in the United States (for reasons other than those related to safety or efficacy).

What Is HPV?

Human papillomavirus (HPV) is a group of around 200 viruses that can infect humans. Of these, around 40 are sexually transmitted.

Some of these HPV types can cause genital warts (papillomas), while others are associated with cancer. These not only include cervical and anal cancer, of which 90% of cases are caused by HPV infection, but also penile cancervaginal cancervulvar cancer, and cancers of the mouth and throat.

In most cases, an HPV infection will spontaneously clear on its own with no long-term consequence. But, in some people, the infection will persist and cause changes to infected tissues, resulting in either warts or precancerous lesions.

Over time, the precancerous lesions can progress to cancer. Genital warts, meanwhile, rarely become cancerous; even so, they are not only unsightly but far more contagious than other types of warts.

The HPV types that cause genital warts are classified as "low risk." The types that have the potential to cause cancer are regarded as "high risk."

A Brief History of HPV Vaccines

Like all vaccines, HPV vaccines work by introducing a substance into the body that triggers an immune response in the form of antibodies. Antibodies are defensive proteins that are produced in response to the specific disease-causing organism. As such, they are "programmed" to recognize that organism and prevent it from establishing an infection.

All HPV vaccines are recombinant vaccines, meaning that they work by inserting the DNA coding from HPV into cells, providing them the instructions on how to produce HPV-specific antibodies. They differ from live attenuated vaccines that use live weakened viruses to trigger the immune response or inactivated vaccines that use killed viruses to do the same.

Over the years, there have been several HPV vaccines approved for use in the United States:

  • Gardasil (also known as Gardasil-4 or quadrivalent human papillomavirus recombinant vaccine) was approved for use in 2006 and protects against two high-risk HPV types (types 16 and 18) and two low-risk types (types 6 and 11).
  • Cervarix (also known as human papillomavirus bivalent vaccine recombinant) was approved in 2009 and protects against two high-risk HPV types (types 16 and 18).
  • Gardasil-9 (also known as human papillomavirus 9-valent recombinant vaccine) was approved in 2014 and protects against two low-risk HPV types (types 6 and 11) and seven high-risk types (types 16, 18, 31, 33, 45, 52, and 58).

The original Gardasil, still in use in certain parts of the world, was discontinued in the United States on May 8, 2017 following the introduction of Gardasil-9. Cervarix was also voluntarily withdrawn in the U.S. on August 8, 2016 but is also still in use in other countries.

HPV Vaccine Evolution

Gardasil-9 is highly effective in preventing infection from certain types of high-risk and low-risk HPV strains.

High-Risk Types

Both the original Gardasil and Cervarix were designed to protect against the two high-risk types—HPV types 16 and 18—that are responsible for the majority of all cervical and anal cancers.

HPV types 16 and 18 account for 70% of all cervical cancers and 84% of all anal cancers.

Focusing on these two HPV types made strategic sense, particularly since cervical cancer used to be one of the leading causes of cancer deaths in women in the United States and still causes around 4,000 death annually. Similarly, anal cancer, while relatively rare, occurs in men who have sex with men at a rate 70 times greater than that of the general population.

However, in the years following the introduction of Gardasil and Cervarix, scientists began to identify other high-risk HPV types.

Among them, types 33, 52, and 58 are known to be highly carcinogenic. Although they are more commonly seen in Asia, they have been identified in women with cervical cancer in the United States as well.

Other high-risk types, like types 31, 33, 45, and 56, are closely linked to specific cancers like penile cancer.

Low-Risk Types

In addition to high-risk HPV types, the original Gardasil protected against low-risk types 6 and 11, which account for over 90% of all genital warts. The rationale: By preventing these contagious subtypes, the rate of HPV transmissions could be reduced if enough children were vaccinated.

Cervarix never protected against either of the low-risk types. With more practitioners turning to Gardasil for HPV vaccination and Cervarix's market share waning, the manufacturers decided to withdraw their vaccine for financial reasons.

Gardasil vs. Cervarix

Another way that the Gardasil vaccines and Cervarix differ is in the manufacturing process in the lab.

To make Gardasil, lab technicians inoculate brewer's yeast (Saccharomyces cerevisiae) with viral proteins. The yeast cells then produce viral-like proteins (VLPs) that are harvested and purified for use in the HPV vaccine. VLP are safe but can provoke a robust, disease-specific immune response.

Cervarix is made similarly by inoculating cells cultured from the fall armyworm moth (Spodoptera frugiperda) with viral protein to generate VLPs.

As similar as these processes are, the method used to produce Gardasil generates a higher concentration of VLPs overall. In fact, Gardasil-9 has three times the concentration of VLPs for HPV type 16 and twice the concentration for HPV type 18 than Cervarix.

Even so, there were ways in which Cervarix is advantageous. Because of the manner in which it binds to cells, Cervarix is able to generate a far longer-lasting antibody response than the original Gardasil.

For this reason, it is the only HPV vaccine approved for use in China, a country with over 100,000 new cervical cancer cases per year. The sustained antibody response means that fewer transmissions can occur. Moreover, unit-per-unit, Cervarix is more cost-effective for China and other developing countries.

With the introduction of Gardasil-9 in 2017, the duration of the antibody response is now regarded as equal to Cervarix, albeit at a higher price ($400 to $500 for the vaccine series).

In terms of safety and immunogenicity (the ability to provoke an immune response), Gardasil, Cervarix, and Gardasil-9 are regarded as equal. They are also equivalent in their ability to prevent the two main types of HPV associated with cervical cancer.


A Word From Verywell

As the only game in town in the United States, Gardasil-9 is regarded as the main form of protection against HPV in the country. The CDC currently recommends HPV vaccination in all boys and girls ages 11 to 12 (before most children are sexually active) and anyone 13 to 26 who hasn't been adequately vaccinated. It can be used in adults 27 to 45, although the benefits may be less.

Despite the CDC recommendations, the rate of HPV vaccination among teens in the United States is lower than almost every other developed country. Where European countries have HPV vaccination coverage ranging from 80% to 90%, the United States hovers below 50%.

Because most states do not mandate HPV vaccination, it is up to you as a parent or a consenting teen or young adult to seek vaccination. The vaccine series requires two to three doses but reduces your risk of HPV infection by around 90%.

HPV Doctor Discussion Guide

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