Views from the London School of Hygiene & Tropical Medicine

HPV vaccines in Brazil. Credit Gabriel Jabur/Agência Brasília

Could a single dose of HPV vaccine be enough?

Mark JitBy Dr Mark Jit, Senior Lecturer in Vaccine Epidemiology.

Year 8 schoolgirls in the UK (12-13 years old) receive two doses each of a vaccine against human papillomavirus (HPV), a virus that causes cervical cancer as well as genital warts and a number of other unpleasant cancers. Until 2013, they received three doses of the vaccine each.

However, in 2011, a team led by Dr Aimee Kreimer at the US National Institutes of Health looked at women who had received fewer than three doses of the vaccine (mostly because they found out that they were pregnant in between doses) in a large trial in Costa Rica. Dr Kreimer and her colleagues found that the women who only received one or two doses of vaccine seemed to be protected just as well from being infected with the HPV types in the vaccine when they were followed up for four years after being vaccinated.

The team’s work led to other investigators looking at the antibody response that women make to two doses of HPV vaccine, as well as mathematical models to extrapolate the likely outcome of giving two doses. Positive findings led to many countries including the UK switching to a two-dose HPV vaccine schedule.

More recently, Dr Kreimer and other investigators conducted a much larger study, combining data from the women in the Costa Rica trial with data from the PATRICIA trial. The PATRICIA trial was a large trial that showed that the efficacy of Cervarix™, one of the currently licensed HPV vaccines.

Their analyses showed again that with this much larger group of trial participants, women who had only received one or two doses of vaccine seemed to be as well protected as those who had three doses. The results attracted a lot of media interest, with many commentators asking whether HPV vaccine schedules could be reduced further to just a single dose. This would save money in places like the UK, but in countries without the resources to buy and deliver two doses of the vaccine, it could really be a “game changer”, in the words of a leading HPV expert.

A group of us at the London School of Hygiene & Tropical Medicine, Public Health England and the University of Laval in Quebec have been using mathematical models to project the long-term impact that HPV vaccines could have on cervical cancer rates. So we took the latest results from these studies and used our models to extrapolate the potential impact that giving just one vaccine dose may have.

Our models show that just that one dose given to 12 year old girls could on its own prevent many of them from having cervical cancer. However, there is still a lot of uncertainty about how long people who just have one dose of vaccine are protected, since women in these studies were only followed for around four years. Hence our models suggest that giving a second dose could bring even larger reductions in the number of women with cervical cancer in the future.

So countries like the UK which already have two dose schedules in place probably shouldn’t switch to one dose until we have more data. However, for countries that have put off introducing HPV vaccination altogether because of financial or logistical difficulties, giving a single dose of vaccine in the interim may be a genuinely beneficial possibility.

Our work was published as a letter in The Lancet Oncology. It was supported by the National Institute for Health Research (NIHR) Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene & Tropical Medicine in partnership with Public Health England.

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Image: HPV vaccines in Brazil. Credit: Gabriel Jabur/Agência Brasília.

1 comment

  1. Paula

    If a 1dose schedule can be achieved that would make HPV vaccination introduction far easier, taking into account the age group targeted (early adolescents, which are not routinely vaccinated). However, I do believe that the two vaccines currently available have some significant differences regarding the type of immune response they elicit (as the adjuvant used is substantially different), hence I think it might be premature to assume that the results from the Costa Rica trial 1) can be inferred for a different vaccine 2) can be used with confidence when no correlate of protection currently exists. What’s more, for one of the vaccine the EMA approved a 2dose schedule in the absence of standard clinical trials with the agreement of follow up studies to ensure that the 2 dose schedule was enough (meaning there is always the possibility of the need for catch up vaccination later in life), so at this point in time it might be premature to discuss 1dose schedules. Last but not least, both vaccines have been licensed for less than 10 years, and cervical cancer is a rather slow progressing disease – coupled with the absence of a correlate of protection, can we so drastically reduce the number of doses needed (3 to 1) with confidence, and in the absence of real life data on long term protection? This holds true for both vaccines, even taking into account current modelling data showing evidence of long term protection for one of the vaccines (for the vaccine types).

    HPV vaccination reduced schedules are a major unmet need, and maybe in countries with solid health systems, like the UK, one can afford the uncertainty of long term protection as screening is strong and catch up vaccination a relatively easy feat in case it would be needed later in life. That is not true in developing countries though, where the need for cervical cancer protection is way higher; if girls were found to be under protected they would hardly ever be reached for catch up vaccination, and still be exposed to disease (whilst believing they were protected).