Human papillomavirus (HPV) is the most common sexually transmitted virus. Around 80% of Finnish women acquire a genital HPV infection in their lifetime. HPV infection by one of the “high risk” HPV types is a necessary cause of cervical cancer, and can also cause cancers of the vagina, vulva, penis, anus, and the back of the throat (called the oropharynx). HPV vaccines are widely in use which can prevent the two most dangerous types of HPV, called HPV16 and HPV18. However, there are twelve types of HPV which are classified by the International Agency for Research on Cancer as high risk for causing cancer.
In the case of certain other infectious diseases, when vaccination has only targeted a subset of pre-existing strains of a bacteria or virus, sometimes the remaining strains have taken advantage of the vacant ecological niche left by the strains removed from circulation by the vaccine. This has sometimes led to an increase in the pre-existing strains not targeted or protected by the vaccine. This phenomenon is called vaccine-induced strain (or type) replacement. Therefore, given that there are multiple types of HPV which may cause genital HPV infection, there has been concern that by removing two types using vaccination, this may lead to an increase in the remaining HPV types.
In Penelope Gray’s dissertation, she has studied whether the two first generation vaccines, known as Gardasil and Cervarix, induce what is known as neutralising antibodies against HPV16 and HPV18 (the two types targeted by the vaccine). The vaccines are thought to work by inducing the vaccinated person to produce neutralising antibodies which can bind to the HPV and prevent it from establishing an infection. She found that women vaccinated with Cervarix had more neutralising antibodies against the HPV16 and HPV18 (the types targeted by both the vaccines) than the women vaccinated with Gardasil. The study also found that the vaccines can induce some antibodies which can also bind to non-vaccine targeted HPV types which are closely related to HPV16/18. However, Cervarix was shown to protect against more closely related non-vaccine HPV types than Gardasil.
Gray then studied how effective the HPV vaccine was under different vaccination strategies. This study randomised different cities over Finland to implement either gender-neutral vaccination or girls-only vaccination. Following the vaccination trial, she then investigated which vaccination strategy provided the most herd protection (decrease in HPV among the women who did not receive vaccination). Gender-neutral vaccination was found to be the most effective strategy at reducing HPV16 and HPV18. HPV16 herd effect (reduction of HPV16 infections among the unvaccinated part of the population) was only observed in the cities which had implemented gender-neutral vaccination.
Penelope Gray then studied the occurrence of the non-vaccine targeted HPV types after this community randomised trial had been implemented. The occurrence of some non-vaccine types, specifically HPV51, 39 and 68 were observed to have increased. However, the increases seen were due to other reasons, and not because of HPV vaccination.
“The key findings of this research are that of the two vaccines, Cervarix produced the best immune response. This is fortunately the vaccine which Finland is currently using in its national vaccination program. Secondly, when vaccination coverage is moderate, gender-neutral vaccination provides herd protection against HPV16 whereas girls-only vaccination does not, and finally, we see no conclusive evidence of the non-vaccine HPV types increasing after vaccination. On the contrary, some closely related non-vaccine HPV types seem to decrease after vaccination. This is good news for the sustainability of HPV vaccination,” says Penelope Gray.
The doctoral dissertation of MHS Penelope Grace Gray in the field of epidemiology titled Human papillomavirus type replacement following the implementation of HPV vaccination will be publicly examined in the Faculty of Social Sciences at Tampere University at 3 o’clock in the afternoon on Friday 2 December 2022. The venue is the Yellow Hall F025 of the Arvo building (address: Arvo Ylpön katu 34). The Opponent will be MBChB Professor Ruanne Barnabas from Harvard Medical School and Massachusetts General Hospital. The Custos will be MD, PhD Professor Pekka Nuorti from the Faculty of Social Sciences.