HPV Vaccination, past & future: An interview with Judith Breuer

Judith Breuer. Photo credit: The COVID-19 Genomics UK Consortium

Professor Judith Breuer FMedSci is Professor of Virology and Co-Director of the Division of Infection and Immunity at UCL, and Consultant Clinical Virologist at Great Ormond Street Hospital for Children. Her research interests include pathogen genomics, molecular epidemiology and pathogen genetic determinants of infectious disease. Although primarily interested in the pathogenesis and spread of viral infections, she has recently applied novel technologies to whole-genome sequencing of hard-to-grow bacteria such as Mycobacterium tuberculosis and Chlamydia trachomatis directly from clinical samples. She is an expert on vaccines and vaccine-preventable diseases, a member of the UK Joint committee on Vaccines and Immunisations and Chair of the subcommittees on Human Papillomavirus and Varicella-Zoster virus vaccines.

Having been involved in the decision to introduce HPV vaccination in the UK in 2008, how do you feel about the news that we are now seeing a dramatic fall in cervical cancer in the cohorts of women covered by the first few years of that vaccination programme?

The results of the paper are great. It was needed, and it was going to happen now that the data has accumulated as the HPV programme has been in place long enough that we can now see the impact of it. It’s great because it’s likely not only showing the direct impact of the vaccination programme, but also the impact of herd immunity. It was predicted and it’s great to see it come true!

Are you surprised at the level of uptake that’s been sustained since the programme’s inception?

I’m not surprised. The UK has a very strong record on implementing vaccines successfully. There are occasional hiccups, but the population is well attuned to taking up vaccines, and I think the delivery of the vaccine as a school-based programme has been amazingly successful – and these school-based programmes have worked very well over the years – going right back to Rubella in the early days. Credit also to the young people who agreed to have the vaccine, they could see the benefit of it both on their lives and on their generation. There’s also been plenty of good news along the way. We very quickly saw a reduction in HPV positive swabs, a fall in cervical smear abnormalities, and now we have a definitive result, which is a fall in cervical cancers.

If you think back to the very beginning in 2007/8, was it difficult to get the programme delivered as a school-based programme?

I wasn’t on the initial committee, but when I joined the JCVI in 2009 by that stage the vaccine programme was already well established. My recollection is that the uptake was good even at that stage. There were some groups raising objections. Some people thought it would drive young people to have more sex, or they might not be as careful as they might otherwise be. As far as my recollection is, none of that impacted on the uptake, it reached high levels fairly quickly.

You will recall the death in 2009 of a 14-year-old girl, Natalie Morton, shortly after she received a dose of the HPV vaccine. Were you involved in the response to that incident? It turned out that she had a malignant tumour in her chest. How important do you think the way the vaccination programme dealt with the situation was to ensure confidence in the safety of the vaccine?

Whenever you’re rolling out something of this scale, to everyone, you do get a background rate of young people dying of unexplained causes, sometimes related to cardiac abnormalities. The chances are with a national programme that at some point someone who dies from an unrelated cause will likely have been recently vaccinated. It’s the same thing that happened with the MMR vaccination. You give every child aged 1 the vaccination, and that’s the age that autism starts to be diagnosed- so the two will be related when it is just chance occurrence on the background of mass vaccination.

It’s interesting that we have seen the impact of anti-vaccination on the MMR vaccination, but uptake for the HPV vaccine has held relatively strong. Do you have any thoughts on why this might be?

There are several reasons why this might be. The MMR issue was already waning, we’d already had big measles outbreaks and deaths from measles. The response of the population to that was to get the MMR vaccine. In HPV we also had highly publicised cases of cervical cancer such as Jade Goody, and that likely helped support the uptake of the vaccine. The notion that this could prevent cervical cancer was a strong driver to get vaccinated. Often with successful vaccines, we lose the memory of how severe the diseases they prevent are, but the memory of cervical cancer was still very fresh. All these things contributed to a belief that the vaccine was worthwhile to have.

HPV uptake in the UK bounced back and has remained high ever since. This is not the case in other countries, such as Japan. Ireland has also seen a dip. What are your thoughts on these differences?

I think it is important to give clear messages about vaccine benefits from many sources as early as one can.  Also, to parry the questions of safety with hard data on the lack of evidence where this is appropriate.  I think we have become better at doing this since the MMR debacle. It’s also important that the workforce has a good knowledge of the vaccines they are using, and they can advise the patients if there are concerns. Finally, a well organised easy to access vaccination service is key. I think we do this very well in the UK and this is reflected in the high uptakes.

Twenty years ago, you studied some strains of human papillomavirus from a different part of the phylogenetic tree from the types that cause cervical cancer. Are the different types of HPV similar enough that one can translate understanding about the virus in one part of the tree so as to develop vaccines in another part?

That’s the principle upon which the recent Merck nonavalent vaccine has been built. The same technology was used to extend the vaccine beyond the most common two variants which are HPV 16 & 18, to include another seven variants which are less common but still contribute a reasonable percentage of cervical carcinoma in this country.  It is also the case the immunity to the two main HPV types 16 and 18 can cross protect against other genital cancer-causing types. The situation with non-genital HPV types is more complex as their surface proteins are more divergent and they would need separate vaccines

Do you think there is the potential to move to a one-dose vaccine programme in the UK?

There’s very good evidence that the levels of antibodies produced after one vaccine dose are extremely high. The big question is how long that antibody lasts. That’s where the subsequent doses have been important, to increase the duration of protection. However, we do now have evidence from people who received one dose inadvertently – where they were part of clinical trials, or they didn’t go back for a second dose – and those people remain very well protected for many years. So, if it is a question of using the bivalent or quadrivalent vaccine, there’s no question in my mind that one dose would be acceptable. There needs to be more research done with the nonavalent vaccine to see what happens to antibody levels over a period of time to see if this new vaccine is behaving as the previous vaccines do. All the evidence is pointing towards one dose becoming the norm, but the JCVI has elected to wait for more data before recommending one dose.

As a career researcher who has been involved with HPV, what advice would you give young people starting out in research?

I did my HPV research some time ago now! I don’t take any credit for the development of the vaccine. Having been in virology since the point in which HPV was first associated with cervical cancer, I feel very privileged to have seen the whole story. The development of the vaccine and the results of this paper prove the original observation that HPV causes cervical cancer. That’s very gratifying, and that’s what science is about. So it’s very important that people remember, we don’t know what the results will be, but we make predictions based on the data we have, and then we test those predictions.

Your Wikipedia entry says that you were inspired by Vera Brittan and Simone de Beauvoir. How did these two great women influence your career, and do you think it is any easier for women to succeed in research today than it was when you started out?

They were answers to a question about who my ideal guest at a dinner party would be! I think I’ve always been inspired by strong and charismatic women. In my scientific career it’s difficult to think of women who have inspired me. There were so few I had contact with while training and in my career. I was fortunate that while at medical school I was taught by some excellent women lecturers, including Sally Davies, who taught me haematology and later became chief medical officer. I hadn’t intended to work in research.   Originally, I was going to go into hospital practice. I went to do some research before applying for consultant jobs, and I enjoyed it so much I decided I wanted to do more of it. I think mentoring is better now. When I was training it was a little bit more hit and miss; not so many people got mentored. I’ve been extraordinarily lucky to get the funding I needed to address research questions, and to have good colleagues with me. I always say to young women, don’t sacrifice your family or your personal life, it’s just not worth it. There’s never a right time to have children, they will always interfere with career plans – so do it when it feels right for you. Don’t give up, if you need to take a sideways step for a few years then do, for both men and women, but don’t give up.

The views expressed are those of the author. Posting of the blog does not signify that the Cancer Prevention Group endorse those views or opinions.

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