The human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases1 which effects 50%-70% of sexually active individuals globally2. Its symptoms include genital warts and cervical intraepithelial neoplasia (CIN) lesions, as well as disease in non-genital sites, including hands, fingers, and face. Previously, cryotherapy was used as a common treatment for treating CIN lesions, by using a probe and freezing the area, and to then destroy that area. However, about 10% to 15% of women with CIN developed a subsequent CIN lesion a few years after cryotherapy2. It was discovered, that the HPV type between the two CIN lesions caused by the HPV infection was not the same, however, the subsequent CIN lesion in AIDS patients contained the contained the same HPV type as the initial lesion. This led to the conclusion that one could develop HPV-type specific immunity after cryotherapy, which further determined that one could develop a vaccine that could protect the population against HPV for the HPV types used in that vaccine2. HPV, however, is not easy to grow in culture, therefore, hollow virus-like particles were synthesized from recombinant HPV capsid proteins by yeast in culture. There are more than 100 types of HPV strains, however, the current vaccination, Gardasil 9, prevents against the most common HPV; 6, 11, 16,18, 31, 33, 45, 52 and 582 and is nearly 100% effective3.
Despite the effectiveness of HPV vaccinations, there are growing concerns on the safety of the vaccine, in light of case reports on autoimmune disorders as an adverse effect of the vaccine. One of these autoimmune diseases is Multiple Sclerosis (MS). MS is a chronic disease of the central nervous system which attacks the myelinated axons and destroys the myelin and axons to different degrees4. The cause of MS is still unknown; however, it is known to involve genetic and non-genetic factors, including viruses and environmental factors4. Parents, especially, are concerned by the onset of Multiple Sclerosis through the administration of the HPV vaccination. A study conducted in two Scandinavian countries dispute this claim5. This study identified a cohort of females between the ages of 10 and 44 years in Sweden and Denmark and followed them between 2006 and 2013. The 3 983 824 participants were split between vaccinated (789 082 participants) and unvaccinated groups in which they were assessed throughout a two-year risk period. The risk period was determined by the fact that the diagnostic delay was estimated to be less than 1 year in more than 50 cases, and accounted for the delay between onset and diagnosis5. The study also considered the onset of MS after this risk period to account for any differences between countries, ages and all other bias. The results show that during the follow-up, 4322 cases of MS were identified between the two groups, 73 of which were vaccinated and diagnosed within the two-year risk period5. There are more incidences of MS in the general, unvaccinated population than there are in the vaccinated population, refuting the claims of those against the HPV vaccination. The results do not support that there are any causal relationships between HPV vaccinations and MS5. Additionally, a study conducted by the Pharmacoepidemiologic General Research eXtention (PGRx) in France confirmed the same results in a more multiethnic group using a different method6. The PGRx assesses risks of rare or delayed health events associated with medication and vaccinations, but in this instance, they looked at the correlation between the HPV vaccine and a multiple set of autoimmune diseases (AD), including MS. Rather than following a cohort after a period of time, the participants were once again split into groups; one being the case or someone who had a manifestation of the set of an AD, and the other being the referent or the control, who had no lifetime history of the AD. The cases were then compared to the referent group to see which one of them had an exposure to any HPV vaccination. Of the 510 participants in the case group, 75 participants had a history of the AD, and 52 of them have had an HPV vaccine6. On the contrary, of the 1953 participants in the referent group, 141 participants had a history of the AD, and 421 of them had taken an HPV vaccine6. As expected based on the previous study, there are fewer people who have had an HPV vaccine and no AD than there have been people with an HPV and have had an AD. In other words, there is a very little risk to developing MS from the HPV vaccination. One factor that differentiates this study from the previous one is that there were more than double the number of participants over a longer period of time (6.5 years), and included participants who were more diverse ethnically and in age6. This would allow the results of the sample group to be more representative of the population as a whole. There are still some limitations with this study as it did not account for any socioeconomic factors which may have had an impact on the results, nor does it account for the extent to which it can be applied to other populations of a similar age. Finally, a Canadian study looked at the effects of the vaccination on Grade 8 girls in Ontario1. By using a self-controlled case series method, the study was able to account for all time fixed factors, such as genetic susceptibility, while time-varying risk factors were accounted for through the Poisson model. After achieving optimal conditions, the study had more than 90% power to find a rate ratio of 2.0 for autoimmune disorders1. Additionally, this study was able to minimize bias towards the null by reducing the longer than recommended risk windows. Nevertheless, despite these robust methods, the results were similar. Of the 681 children who had been given the HPV vaccine, only 17 people (2.4%) had an onset of MS1.
Despite the overwhelming amount of evidence pointing against MS as an adverse effect of the HPV vaccine, many people still refuse to take the vaccination. A common rebuttal of the anti-vaxxers is to look at case studies in which children are affected by MS and think there is a correlation between MS and the vaccine itself7. Previous vaccine studies mention an unmasking phenomenon, in which the vaccination can provide the opportunity to evaluate otherwise unnoticeable symptoms5. This results in a bias towards the association between the vaccination and the adverse effect. Another argument is that HPV is a common STD and very rarely develops into cancer, therefore the risk of HPV is less severe than getting vaccinated and developing MS. This is incorrect as HPV types 16 and 18 are known to cause cervical lesions and are responsible for up to 80% of all cervical cancers6.
In conclusion, Multiple Sclerosis is not caused by the HPV vaccination. It is justifiable to continue using the HPV vaccination at a population level. Despite the slight risk of getting multiple sclerosis, or any other autoimmune disease, there is no direct association with the vaccination itself. If cancer is preventable, it is more appropriate to take an upstream approach and minimize the risk of the disease. Vaccinations are used as a way to improve population-level health as a whole and minimize the cost of health care. If there is no correlation between MS and HPV, it would not make any sense to worry about a slight risk when there is a greater chance of developing cancer. The findings should provide reassurance to health care providers and parents in ensuring a healthy childhood.