The Story Behind the Discovery of the HPV Vaccine

The world's first cancer-specific preventive vaccine was not developed by a pharmaceutical company. HPV vaccine discovery was supported by public institutions on two continents, including three universities and the United States National Cancer Institute. The vaccine prevents infection that can cause cervical cancer, specifically infection with human papillomavirus (HPV) . HPV spreads mainly through sexual contact, and approximately %80 of both men and women become infected at some point. Just as smallpox vaccination made smallpox no longer a problem today, HPV vaccination appears capable of preventing HPV-related cancers, particularly cervical cancer, before they develop.

HPV is considered responsible for %5 of all cancers, and cervical cancer alone is estimated to kill 300.000 women worldwide annually.

- Related topic: What Is a Virus? A Brief History of Viruses and Cancer-Causing Viruses

How Does the HPV Vaccine Work?

The HPV vaccine is based on virus-like particles (VPL). These particles share the virus's outer protein coat (L1), but lack HPV's infectious genetic material. The key to the vaccine is the external protein coat: it makes the immune system perceive the particles as actual HPV, generating an immune response without any exposure to the virus through vaccination. Unlike an influenza vaccine, it is not an attenuated form of the virus; it is not even a virus.

Creating the HPV vaccine took more than 20 years. Georgetown University researchers received the dominant HPV vaccine patent for their early background research, although the Georgetown team had never worked with virus-like particles. They showed that the L1 protein coat's natural structure, or normal form, was necessary for virus-like particles to form.

3 Universities, 4 Research Groups and at Least 4 Patents

The United States Patent Office also approved patent claims from the United States National Cancer Institute, the University of Queensland in Australia and the University of Rochester in the United States. Queensland researchers published data on two protein coats, L1 and L2, reporting that these structures allowed virus-like particle assembly, but that the particles were small and incorrectly assembled. Publication before Georgetown's paper caused debate about ownership of the dominant patent.

United States National Cancer Institute researchers independently produced the first virus-like particle capable of eliciting an immune response in animals.

The University of Rochester team performed the first studies demonstrating immune responses in humans.

HPV research at Australia's University of Queensland was led by Dr. Ian Frazer . Some patents were sold to Merck and Australia's CSL Limited to fund research. The United States National Cancer Institute funded the Georgetown and Rochester teams.

These four groups did not collaborate, but their academic efforts enabled rapid and effective discovery of virus-like particles. Most findings leading to the HPV vaccine were published between 1991-1993.

The Three Vaccine Types

There are currently 3 HPV vaccines: 2-valent (bivalent), 4-valent (quadrivalent) and 9-valent (nonavalent).

Quadrivalent Gardasil and bivalent Cervarix are available in our country. The nonavalent vaccine received, in 2014, FDA approval.

• The first HPV vaccine on the market, Gardasil, was produced by Merck and protects against four HPV types. This includes HPV-16 and HPV-18, which together, these 2 types, cause %70 of cervical cancers. HPV-16 is also associated with head and neck cancers . Gardasil also protects against HPV-6 and HPV-11, thereby protecting against %90 of genital warts. 
• Produced by GlaxoSmithKline, Cervarix was approved in the United States in 2009 after several years of worldwide use and protects only against high-risk HPV types 16 and 18. It therefore does not prevent genital warts. A United States National Cancer Institute study suggests two of the recommended three Cervarix doses may suffice for protection. This is notable because patients may miss the third dose, scheduled six months after the first injection. Cervarix also appears effective for 7 years after administration. 
• To protect against HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58, Gardasil 9 was developed.

Who Should Receive HPV Vaccination and When?

• For girls and women, between ages 9-26; for males, vaccination between ages 9-21 is recommended.
• Age matters for HPV vaccine immunity. The ideal age for both sexes is recommended as 11-12. However, your doctor may recommend vaccination from age 9.
• HPV vaccination before first sexual contact is important. Against the 4 most common HPV types, children not previously exposed to HPV can obtain %100 protection through vaccination. 
• Routine HPV vaccination is recommended to begin at 11-12. For ages 9-14, a 2-dose schedule is planned, with the second dose 6 to 12 months after the first. 
• For children and adolescents aged 9-14, if less than 6 months separate 2 HPV vaccine doses, a third is recommended. However, if at least 6 months separate the doses in this age group, 2 doses are reported sufficient. 
• Adolescents and young adults beginning vaccination at ages 15-26 are advised to receive 3 doses to protect against cancer-causing HPV infections. 
• Children and young people of both sexes aged 9-26 with weakened immune systems are recommended to complete three doses.

Early HPV vaccination is important because it provides substantial protection against many HPV-associated cancers, especially cervical cancer. Although reports indicate recommendations up to age 45 in Australia, doubts remain about achieving the desired effectiveness after age 26. Gardasil 9, the vaccine effective against 9 HPV subtypes that we hope will soon become available, is expected to offer better protection. In conclusion, vaccination is an effective and safe way to prevent HPV infection and the many diseases it can cause. 

Related Topics:

- Can HPV Pass from Mother to Baby During Pregnancy? How Does It Spread, and Can It Be Prevented?

- From World War 2 to the Nobel Prize: Dr. Harald zur Hausen and the Discovery That HPV Causes Cervical Cancer

- George Papanicolaou, Who Saved Millions of Women's Lives with the Pap Smear

- AUTISM: Its Relationship with Vaccines, Special Diets and Cancer