This spring marks the 6-year anniversary of the vaccine for HPV, a common sexually transmitted infection that causes warts, cervical cancer, and other cancers. Since the vaccine’s debut back in 2006, millions worldwide have been vaccinated against HPV —an effort which is expected to have a serious impact on reducing the incidence of cervical and other anogenital cancers around the globe.
What’s now a commonplace vaccine, however, represents a long (and occasionally weird) history of scientific discovery. On this 6-year vaccinaversary, let’s nerd out for a minute and revisit the complex, sometimes strange, and ultimately successful history of the HPV vaccine.
In a time where there were no microscopes or stethoscopes, many important scientific discoveries were made on the basis of observation. Hippocrates – the same guy who wrote up the “Hippocratic oath”—recognized the appearance of warts as far back as 400 BC. A few hundred years later (~25 AD), Aulus Cornelius Celsus identified distinct types of warts: acrochordon (“skin tags”), thymion (genital warts), and myrmecia (non-genital warts). Though warts were well-described at this point, they were probably regarded as little more than a nuisance, and the cause of warts wasn’t understood for another thousand years.
1842-1910: Nuns, Sex Workers and Transmissibility
Antonio Rigoni-Stern, an Italian physician, was a bit of an epidemiologist before the field formally developed. He studied population-level disease trends in women by examining death certificates. Observing that cervical cancer was more common among sex workers than nuns, he hypothesized that cervical cancer was related to sexual contact. [Not all of Rigoni-Stern’s hypotheses turned out to be as accurate. He also hypothesized that breast cancer was more common among nuns because their corsets were too tight.] In the late 1800s and early 1900s, other scientists made the observation that warts appeared to be transmitted through personal contact. By noting that both warts and cervical cancer could be transmitted by personal and sexual contact, these scientists helped elucidate that HPV may be transmitted through skin-to-skin contact. However, HPV itself was not yet identified, and it was not yet known that cervical cancer and warts shared a common cause.
1933-1955: The Jackalope Years
In the 1930s, Richard Shope was the first to isolate the virus responsible for flu. Previous to Shope’s work, it had been theorized that microbial agents were causing flu, but never before had the virus been isolated as a causative disease agent.
After his seminal flu research, Shope directed his attention (where else?) to rabbits. He looked at wart-like growths on rabbits’ paws and determined that they were caused by a virus, which was named “Shope” papilloma virus (SPV) after his work. SPV also appeared to cause a more serious condition whereby cottontails developed horn-like projections on their heads and faces. Shope and his colleague Francis Peyton Rous determined that the horn-like projections were in fact SPV-related tumors. This discovery essentially ended the legend of the “jackalope”, as it turned out that jackalopes were probably just cottontail rabbits with a papillomavirus infection. But, the idea that a virus could in fact cause tumors was a huge, game-changing idea in the scientific community.
HPV research moved incredibly quickly in the 1970s and 80s, due in part to major technological advances in serology and genetic sequencing. By 1980, HPV had been identified, and in the years that followed, scientists were able to sequence HPV and explore its role in human disease. Dozens of HPV serotypes were characterized, appearing to have different effects in humans: some caused genital warts, and others appeared to have no effect in disease. In the early 1980s, scientists such as Syrjänen, Boshart and Durst characterized HPV-infected cells in esophageal and cervical cancer biopsies. Although HPV appeared to be associated with these cancers, however, there wasn’t yet concrete evidence for HPV causing cancer in humans.
During the late 1980s and 1990s, evidence emerged to support a causal role between HPV infection and cervical cancer. That an infection could cause cancer provided tremendous promise, as it meant that a vaccine against the infection could eliminate cervical cancer altogether. After HPV was shown to be causally associated with cervical cancer, scientists in various fields began working to identify vaccine targets that would effectively illicit an immune response in humans. By 2005, an HPV vaccine target had been selected. Safety and efficacy trials began, and the first HPV vaccine (Gardasil) was shown to be effective in preventing many (>70%) cervical cancer cases and genital warts. Gardasil was released in 2006 to women for the prevention of cervical cancer and genital warts.
So there you have it—the history of how the HPV vaccine was born. From noting that warts and cervical cancer may be transmitted through person-to-person contact; to discovering that a papillomavirus could cause cancer in rabbits; to establishing a causal link between some types of HPV and cervical cancer in humans; to the ultimate development of Gardasil.
Six years after its original debut, the vaccine is now approved for both women and men in the prevention of genital warts, cervical cancer and anal cancer. There’s also some evidence to support that HPV vaccination may have additional benefits in preventing some head and neck, vulvar, and vaginal cancer. Along with the pap smear, the HPV vaccine has become an important component of cervical cancer prevention, and may have a place in preventing other types of cancers as well.
For more information on HPV in general, see our blog post on HPV frequently asked questions. If you’re curious about getting the HPV vaccine on campus, see the Campus Health Services page for more information.