While a “cure” for cancer remains elusive, prevention of some cancers is within our grasp. It is estimated that 30 – 50% of cancer cases are preventable through risk-reducing measures. One simple method involves just two shots of the human papillomavirus (HPV) vaccine during childhood. This vaccine not only protects against HPV infections, but also reduces the risk of developing cancers caused by HPV.
In the late 1960s, the herpes simplex virus type 2 (HSV-2) was a prime suspect as the cause of cervical cancer. Virologist Harald zur Hausen attempted to find HSV-2 DNA in cervical cancer biopsies, but to no avail. Upon learning that genital warts, previously shown to contain papillomavirus, could become cancerous, Dr. zur Hausen connected the dots. His research group was able to identify DNA from HPV in cervical cancer biopsies and characterize the integration of viral genes into the host cells. His pivotal work in discovering HPV as a causal agent of cervical cancer was recognized in 2006 with a Nobel Prize in Medicine.
HPV is now established as a cancer-causing, or oncogenic, pathogen that is the primary cause for anogenital (cervical, anal, vulvar, vaginal, and penile) cancers and oropharyngeal (throat) cancers. It represents a group of related viruses with double-stranded DNA, encompassing more than 100 different types. The virus is transmitted by skin-to-skin contact and commonly contracted through sexual intercourse.
HPV infections are, in fact, very common. The majority of sexually active individuals become infected at some point in their lives. Most infections resolve on their own, often without any symptoms. Yet, HPV accounts for a staggering 90% of cervical and anal cancer cases.
It all comes down to the type of HPV: While an infection with a low-risk type may be harmless, a long-persisting infection with specific oncogenic HPV variants can transform normal cells into cancerous ones. HPV types 16 and 18 are highly oncogenic and responsible for approximately 72% of HPV-attributable cancer cases. The rest are associated with HPV types 31, 33, 45, 52, and 58.
The research linking HPV to cervical cancer catapulted the development of vaccines for HPV. Immunologist Ian Frazer and virologist Jian Zhou developed virus-like particles (VLP) of proteins from the surface layer of HPV. VLPs closely resemble the virus but cannot mount an infection. HPV vaccines based on VLPs train the immune system to recognize and clear the virus in subsequent encounters – before it leads to a persistent infection that could trigger the oncogenic process.
There are two different HPV vaccines available in Canada: HPV9 vaccine (Gardasil-9) by Merck and HPV2 vaccine (Cervarix) by GlaxoSmithKline. Both VLP-based vaccines protect against oncogenic HPV types 16 and 18, which cause most HPV-attributable cancers. Gardasil-9 protects against an additional five oncogenic HPV types (31, 33, 45, 52, and 58) along with two genital wart-causing types (6 and 11). Currently, only Gardasil-9 is authorized for use in both sexes in Canada.
Both vaccines have demonstrated their safety in large-scale clinical trials involving 15 000 – 30 000 participants and in continued safety surveillance. Cervarix and Gardasil-9 have a >90% efficacy against HPV type 16 and 18-related cervical cancer. Likewise, immunization with HPV4 vaccine (Gardasil), an early predecessor to Gardasil-9, showed 84-100% efficacy against HPV-associated genital lesions in men. Vaccine efficacy against vaccine-type specific oral HPV infections has been reported to be similarly high, ranging from 88% to 93% depending on the sampled population. Moreover, studies following vaccinated individuals for more than 10 years provide evidence that the protection is sustained long-term.
As a preventative measure, the HPV vaccine is most effective when administered before exposure to the virus or start of sexual activity. Further research on vaccination of girls and young women between the ages of 14 and 26 years reveal the additional benefit of improving herd immunity, which provides indirect protection to unvaccinated individuals through immunization of a significant portion of the population.
In Canada, as part of routine childhood immunization, two doses of HPV vaccines 6 to 12 months apart are recommended for children (girls and boys) aged 9 through 14 years. Subsequently, ‘catch-up’ vaccinations with three doses are recommended for youths and young adults between the ages of 15 to 26 years and remain available for adults between the ages of 26 to 45 years.
As of 2017, all Canadian provinces and territories have school-based immunization programmes that offer publicly funded HPV vaccination, most commonly, in Grades 6 or 7. In 2017, the rate of full-dose HPV vaccination within the target adolescent demographic ranged by province/territory from 57% to 91%. These figures markedly declined amidst the COVID-19-related disruptions of schools, emphasizing the importance of school-based delivery of vaccination.
Publicly funded HPV vaccinations continue to be accessible for individuals eligible for catch-up programs through healthcare providers. However, if ineligible, the three-dose HPV vaccine series can cost over $600. Other barriers to vaccination include lack of information or awareness about the vaccine and inequities in accessing care, which disproportionately impact Indigenous peoples, rural and remote communities, people with low income, and 2SLGBTQI+ individuals.
While vaccination against HPV has now been adopted by national vaccination programmes in more than 130 countries, the World Health Organization estimates that only 21% of girls worldwide have had their first dose. Limited or lack of access to affordable vaccination poses a major barrier in many low- and middle-income countries, which face the highest burden of deaths from cervical cancer. To address the disparities in childhood immunization, UNICEF is working to supply HPV vaccines to 52 countries and to introduce them into routine vaccination programmes of more countries.
The advent of HPV vaccine marks the culmination of many breakthroughs in research. It has given us the opportunity to control a known preventable risk factor for many types of cancers. However, much work remains to done in improving vaccine coverage so that more people can benefit from this life-saving vaccine.
Nasana Vaidya
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