In 400 BC, Hippocrates described bumps on people’s skin in his writings as “condylomata.” He linked these bumps, which were warts, to sexual activity, but human papillomavirus infection (HPV), the true cause of these warts, would not be revealed until centuries later (1). By the 1800s, doctors had correlated these warts to sexual activity, as they saw that these warts appeared more in women who were sexually active, but they didn’t know why (2). In 1949, Strauss and colleagues visualized virus-like particles from skin papillomas using electron microscopy, laying the groundwork for the later identification of HPV (1).

In the 1970s, Harald zur Hausen hypothesized that HPV caused cervical cancer. By the 1980s, he discovered HPV 16 and HPV 18, which together account for around 70 % of all cervical cancer cases (3). In 2019, HPV caused an estimated 620,000 cancer cases in women and 70,000 in men worldwide (2).

HPV is the name of the virus that infects humans (2). Papillomaviruses (PV) can also infect non-human mammals as well as birds, turtles, snakes, and fish (1). It is theorized that PV originated hundreds of millions of years ago and evolved into the HPV that infects humans today. However, scientists are still far from fully understanding PV evolution.

HPV enters through tiny cuts in the skin and hides in the cells. Although the immune system clears most HPV infections, the virus can evade immune defenses through various strategies. HPV is responsible for warts, precancerous lesions, and cancer itself. In fact, almost all cervical cancer in women is caused by HPV (4). Initially, doctors could only treat these warts, lesions, and cancers with pharmacological and surgical therapies such as drugs, surgery, radiotherapy, and chemotherapy. They had no way to prevent or target the virus itself — until the HPV vaccine (5).

In 1984, Ian Frazer visited Harald zur Hausen in Germany, which led to his interest in HPV infection and his meeting with Jian Zhou in 1989. These two scientists found a way to copy the outer shell of HPV, called capsids. These capsids acted like a “wanted poster” for the immune system, allowing it to recognize and attack the virus before it infected the body. Frazer and Zhou had to prove they were the first to discover the technology in U.S. patent court and persuaded vaccine companies and developers to pursue the HPV vaccine. Eventually, their discovery led to the development of the first preventative HPV vaccines (6).

The first two vaccines were Gardasil and Cervarix. HPV has many genotypes, and these vaccines protected against the most prevalent and dangerous ones. Gardasil targeted HPV 6, 11, 16, and 18; Cervarix targeted HPV 16 and 18. In 2014, Gardasil 9 was introduced, covering HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58. In the United States, Gardasil and Cervarix were discontinued after Gardasil 9 became the standard.

HPV vaccines demonstrated over 90 % efficacy in preventing high-grade precancerous lesions (e.g., CIN 2+/CIN 3+) caused by vaccine-targeted types in HPV-naïve populations (2). Countries such as the U.S., Australia, and Canada implemented national vaccination programs, focusing on school-aged children.

In Canada, the federal government invested $300 million in 2007 to support provinces in launching school-based vaccination programs for girls aged 9–14. Provinces began including boys starting in 2013, and today, programs are gender-neutral across the country. Studies show that vaccinated Canadian teens are far less likely to develop HPV infections or abnormal cervical cells that could lead to cancer (7, 8).

More and more HPV vaccines are being registered globally. For example, Cecolin and Walvax recombinant HPV vaccine have been approved in China, and Cervavac was introduced in India. In addition, therapeutic HPV vaccines are currently in clinical trials; while none are yet approved, early studies show promising results in treating HPV-related lesions (2).

HPV vaccines have already saved millions of lives and are among the first vaccines proven to prevent cancer — following the Hepatitis B vaccine, which prevents liver cancer. Many experts believe that by the end of this century, cervical cancer could be eliminated, thanks to HPV vaccination.

The Story of HPV and Its Vaccine-Centre for New Immigrant Well-Being (CNIW)

References

  1. Harari A, Chen Z, Burk RD. Human Papillomavirus Genomics: Past, Present and Future. In: Ramírez-Fort MK, Khan F, Rady PL, Tyring SK, editors. Current Problems in Dermatology [Internet]. S. Karger AG; 2014 [cited 2025 Aug 20]. p. 1–18.
  2. Mlynarczyk-Bonikowska B, Rudnicka L. HPV Infections—Classification, Pathogenesis, and Potential New Therapies. Int J Mol Sci. 2024 Jul 11;25(14):7616.
  3. Yousefi Z, Aria H, Ghaedrahmati F, Bakhtiari T, Azizi M, Bastan R, et al. An Update on Human Papilloma Virus Vaccines: History, Types, Protection, and Efficacy. Front Immunol. 2022 Jan 27;12:805695.
  4. Williamson AL. Recent Developments in Human Papillomavirus (HPV) Vaccinology. Viruses. 2023 Jun 26;15(7):1440.
  5. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses. Lyon, France Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer; 2007. (IARC monographs on the evaluation of carcinogenic risks to humans).
  6. Frazer IH. The HPV Vaccine Story. ACS Pharmacol Transl Sci. 2019 Jun 14;2(3):210–2.
  7. Steben M, Tan Thompson M, Rodier C, Mallette N, Racovitan V, DeAngelis F, et al. A Review of the Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: 10 Years of Clinical Experience in Canada. J Obstet Gynaecol Can. 2018 Dec;40(12):1635–45.
  8. Kim J, Bell C, Sun M, Kliewer G, Xu L, McInerney M, et al. Effect of human papillomavirus vaccination on cervical cancer screening in Alberta. Can Med Assoc J. 2016 Sep 6;188(12):E281–8.

by Jakie Zhou