An Extremely Successful Vaccine Story

by Gertrud U. Rey

One of the most noteworthy advances in biomedical science is the vaccine for human papillomavirus (HPV). It has significantly changed the diagnostic and prognostic landscape in the field of cervical cancer. Cervical cancer is the fourth most common cancer in women globally, and it is a particular problem in low-income countries and for women living with HIV. Since the FDA approved the initial HPV vaccine in 2006, the incidence of cervical cancer is substantially lower among individuals who were immunized before age 14.

German virologist Harald zur Hausen initially made the connection between HPV and cervical cancer in the early 1980s, when he isolated and identified HPV type 16 (HPV-16) and HPV type 18 (HPV-18) from cervical cancer tumors. Subsequent research showed that 99% of cervical cancer cases are linked to prior infection with HPV, and that HPV-16 and HPV-18 are responsible for the majority of these cases. Zur Hausen’s findings provided the foundation for the development of all HPV vaccines, and he was awarded the 2008 Nobel Prize in Physiology or Medicine for his discoveries.

There are currently six licensed HPV vaccines, sold under the tradenames Cervarix, Cecolin, Walrinvax, Cervavax, Gardasil, and Gardasil 9. Cervarix, Cecolin, and Walrinvax are bivalent formulations that protect against HPV-16 and HPV-18. Cervavax and Gardasil are quadrivalent vaccines that also protect against HPV-6 and HPV-11 in addition to HPV-16 and HPV-18. Gardasil 9 is the only HPV vaccine used in the US, and as its name implies, it protects against 9 strains: HPV-6, -11, -16, -18, -31, -33, -45, -52, and -58. These are the main HPV types associated with cervical cancer tumors. All HPV vaccines consist of hollow virus-like particles lacking viral DNA and are composed of recombinant inactivated L1, the main structural capsid protein of HPV. For example, Gardasil 9 contains inactive L1 proteins from each of the nine different HPV strains listed above. The vaccines are designed to stimulate production of antibodies that neutralize the respective HPV viruses, thus preventing infection with any of the HPV strains in the vaccines.

Since the original HPV vaccines were introduced, their effectiveness in preventing HPV disease and cervical cancer has been documented extensively. To demonstrate this effectiveness, I briefly summarize three reports published within the last year. A retrospective study based on routinely collected data on all women in Scotland born between 1988 and 2016 showed that the bivalent vaccine Cervarix dramatically reduced and prevented the incidence of invasive cervical cancer. There was not a single recorded case of invasive cervical cancer in the 40,503 women who had been immunized at age 12 or 13, regardless of how many doses they had been given; and the 99,516 women who received three doses between age 14 and 22 were significantly less likely to develop cancer compared to all unvaccinated women. These results suggest that vaccination of girls at the recommended age of 11 provides complete protection against cervical cancer. 

The investigators of a population-based study in Texas analyzed data from the local immunization registry and various other epidemiological databases, which collectively involved more than 54.7 million participants in different Texas counties between 2006 and 2022. They found that there was a higher prevalence of HPV-related cervical cancer in counties in North Texas, where there was reduced HPV vaccine availability and a lower rate of vaccination compared to counties with higher vaccine uptake. These data suggest that HPV vaccination has a real, positive impact on disease outcome in immunized individuals. A more recent, nationwide epidemiological survey evaluating the cervical cancer mortality rates in US women between 1992 and 2021 showed that there was a 12% per year decline in cervical cancer incidents between 2012 and 2019, representing an overall 65% reduction in cervical cancer. Taken together, these studies clearly illustrate the long-term effectiveness of the HPV vaccines in preventing cervical cancer in multiple different populations and settings.

Although HPV vaccination was initially only recommended for girls and young women, it quickly became evident that vaccinating boys would automatically also protect the girls with whom they come in contact. Moreover, the HPV vaccine prevents anal, penile, and head and neck cancers in addition to cervical cancer, thus further supporting the notion that both boys and girls should be vaccinated.

Some people are concerned that HPV vaccination may encourage earlier and risky sexual behavior in young vaccine recipients. However, these concerns are unwarranted, because multiple studies indicate that there is no association between HPV vaccination status and subsequent sexual activity. Young girls in particular appear to be aware of their risk of acquiring other, non-HPV-related sexually transmitted diseases and believe that safe sex behaviors like condom use are still necessary even after vaccination against HPV. There is also no evidence to suggest HPV vaccination causes young vaccine recipients to engage in sex earlier than they would if they were not vaccinated. In sum, the evidence is strongly in favor of immunizing both boys and girls with the HPV vaccine during their early teens in order to prevent cervical cancer and other cancers caused by HPV.