Gender-neutral HPV vaccination best at preventing cervical cancer

The most effective way to prevent cervical cancer is to give HPV vaccines to both boys and girls, reports a collaborative study involving researchers from Karolinska Institutet published in Cell, Host and Microbe. Beside personal immunity, such use of the vaccine also induces a herd immunity that will help to eradicate the carcinogenic virus types more quickly. 

The human papillomavirus (HPV) comprises over 200 virus types. A viral infection usually clears up on its own, but some HPV types can eventually, after many years, give rise to different kinds of cancer, of which cervical cancer is the most common.

The HPV vaccine has been around since 2006. Initially, it was given exclusively to girls around the age of 12, but since August 2020, the HPV vaccine has been offered to both boys and girls in the year-five general vaccination programme.

The researchers behind the present study have looked at how the composition of HPV types changes over time in post-vaccination populations. This they studied in 33 different towns in Finland, which were randomly assigned to vaccinate boys and girls, to vaccinate girls only or to offer no vaccination at all.

The study included children born between 1992 and 1994 who were followed up at the age of 18 ( over 11,000 individuals) and 22 (over 5,500 individuals), representing four and eight years after vaccination. The vaccine used then protected against HPV types 16 and 18, which cause 70 per cent of all HPV-related cervical cancers, but also transpired to provide cross-protection against types 31 and 45. The vaccine coverage rate was up to 50 per cent.

“The fact that the HPV vaccine study randomised the communities to different treatment programmes is what enabled us to study the effects of vaccination,” says the study’s first author Ville Pimenoff, docent of evolutionary medicine at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet.

The results show that eight years after vaccination, the prevalence of HPV types 16 and 18 declined significantly in the 22 towns in which the vaccine was provided. In the eleven towns that only vaccinated girls, there was a decrease in HPV 31, while in the eleven towns that vaccinated girls and boys, there was a clear decline in both HPV 31 and 45.

“This shows that you get stronger herd immunity if you vaccinate both boys and girls,” says Dr Pimenoff. “According to our calculations, it would take 20 years of vaccinating girls to achieve the same effect that can be achieved in eight years with a relatively moderate vaccination coverage rate of gender-neutral vaccination.”

The researchers are also able to show that the virus types eliminated by the vaccine were replaced by other HPV types of low oncogenecity, a claim that was once moot but that has now, say the researchers, been confirmed. 

This means that although the risk of cancer from the virus types against which the vaccine protects is negated, the risk of cancer per se is not eliminated, since they are replaced by low-risk virus types.

“The HPV vaccine is effective against the high oncogenetic HPV types and studies, including our own, show that there is no reason to be concerned about the observed increase of low oncogenetic HPV types since they very rarely cause cancer,” Dr Pimenoff continues.

A vaccine is also now used that targets nine different virus types, including some of those that were observed to increase in the current study.   
The changes in virus type composition also have consequences for the cervical screening that runs parallel to the vaccinations. Here the search is for high-risk HPVs, such as 16 and 18.

“But as more and more vaccinated women reach screening age, we’ll have to start testing them at another frequency or stop altogether,” says Dr Pimenoff.

The study was a collaboration among researchers at Karolinska Institutet and the universities of Tampere (Tammerfors), Uleåborg and Lund. It was financed by the Cancer Foundation of Finland, the Swedish Cancer Society, and the EU Horizon 2020 programme. The researchers report no conflicts of interest. 

Fact: 
HPV is the most common sexually transmitted infection in Sweden. While a majority of all sexually active men and women become infected, the related cancer rate is low. For example, the annual incidence of HPV-related cancer in Sweden is 800 for women and 300 for men. The vaccine currently offered in Sweden protects against nine HPV types: 6, 11, 16, 18, 31, 33, 45, 52 and 58.
Source: The Swedish Public Health Agency.