November 8, 2023

expert reaction to study suggesting re-evaluation of HPV screening strategies due to cancer-causing HPVs depleted by vaccination

A study published in Cell Host & Microbe looks at the re-evaluation of HPV screening strategies.

Prof Anne Mackie, Director of Screening for the UK National Screening Committee (UK NSC), said:

“The UK National Screening Committee (UK NSC) welcomes this new paper.

“However, more research is needed and the UK NSC has commissioned a modelling study to help understand the likely impact of potential alternative screening strategies on the vaccinated cohort in the future.

“The routine offer of HPV vaccination for girls started in 2008 and has successfully reduced the risk of infection in younger age groups.

“However, most women in the eligible age range for screening (25 to 64) have not received the vaccine and may have been exposed to infection previously.

“A high quality cervical screening programme will continue to prevent cases of cervical cancer in this non-vaccinated population over the coming decades.”

Prof Stephen Duffy, Professor of Cancer Screening, Wolfson Institute of Population Health, Queen Mary University of London (QMUL), said:

“This is an interesting and well conducted study of the community-level effects of HPV vaccination, with two major findings. First, that immunising both girls and boys against oncogenic human papillomavirus is the best policy. Second, that there is evidence of other HPV types ‘filling the gap’ left by those oncogenic types targeted by the vaccine. While we should not rush to change screening policy as a result of one study, it would be prudent to check if these results are replicated elsewhere, and to consider the implications for which populations we screen and how we screen them.”

Dr Tim Fenton, Associate Professor in Cancer Biology, University of Southampton, said:

“The HPV types the investigators found in vaccinated populations confer considerably less risk of cervical cancer than the major cancer-causing HPV types, 16 and 18, against which the vaccine was designed to protect. The significance of detecting one of these types in cancer screening is less clear cut, and the benefits of screening to prevent cancer need to be weighed carefully against the prospect of putting people through unnecessary anxiety and follow-up procedures when the risk of an HPV infection with one of these HPV types eventually resulting in cancer is much lower.

“One point to note is that this study was based on individuals that received the bivalent HPV vaccine (Cervarix), which was designed based on HPV16 and HPV18. The vaccine now being given through the UK vaccination programme (Gardasil 9) was designed to protect against 7 cancer-causing HPV types, plus two types (6 and 11) that cause genital warts. Since Gardasil 9 should protect us from several of the HPV types whose prevalence increased among vaccinated populations in this study, this may become less of an issue in future. It will remain important to monitor the prevalence of all carcinogenic HPV types in the population.”

Prof Margaret Stanley, Emeritus Professor of Epithelial Biology and Research Visitor in the Department of Pathology, University of Cambridge, said:

Does the press release accurately reflect the science?       

“Oversimplifies a very complex study, that combined analysis of changes to the virome, the viral ecosystem responding to removal of the dominant species as a consequence of vaccination in a complex trial but then speculates about crucial public health interventions.”

Is this good quality research?

“Yes, but very reliant on modelling and statistical analysis.” 

Are the conclusions backed up by solid data? 

“The analyses are done to a very high standard but the vaccine coverage in the trial in some cohorts is sub-optimal.”

How does this work fit with the existing evidence? 

“There have been recent reports of an increase in HPV52 in vaccinated cohorts so there is a body of evidence developing to support this.” 

Have the authors accounted for confounders? 

“Yes rigorously.”

Are there important limitations to be aware of? 

“Yes, the vaccine coverage in the trials in different communities varies and in some is very low, the authors have used very sophisticated statistical test to account for this but it does lead to a concern about bias.”

What are the implications in the real world? 

“The vaccination of boys is important particularly where girls’ uptake is low. Vaccinating boys as well as girls reduces the amount of virus circulating faster and more effectively than immunizing girls only – the herd effect.  Herd immunity or herd protection occurs when enough people in the population are immune then transmission of virus from one person to another becomes a rare event and non-immune people are protected.  Girls-only vaccination for HPV herd immunity requires 90% of girls to be vaccinated year on year since only half of the population is being protected but immunizing boys starts to protect the other half of the population and the virus has nowhere to go.

Is there any overspeculation? 

“The suggestions about re-evaluation of screening are premature. Screening by HPV testing albeit with fewer screens for a woman during her lifetime must continue until the evidence shows that the elimination target for cervical cancer of an ASR (age standardized rate) of <4/100,000 will be reached.  An important take-home message from this study is that rigorous surveillance of HPV infection and disease in the post-vaccination era is imperative to monitor potential changes in the HPV ecosystem in the cervix and any impact on disease – we shouldn’t take our eye off the ball.”

Does this study provide enough/robust evidence to suggest we should reevaluate/stop the current HPV screening programme in the UK?

“No, the findings are very interesting but evidence from national immunisation programmes with high coverage and good surveillance of HPV infection and disease pre- and post-vaccination is needed before re-evaluation of screening programmes and strategies.” 

‘Ecological diversity profiles of non-vaccine-targeted HPVs after gender-based community vaccination efforts’ by Ville N. Pimenoff et al. was published in Cell Host & Microbe at 16:00 UK Time Wednesday 8 November 2023. 

DOI: 10.1016/j.chom.2023.10.001

Declared interests

Prof Margaret Stanley: My potential conflict of interest is that I was a member of the Scientific Advisory Board for this PHASE IV trial.

Prof Stephen Duffy: I have no conflict of interest.

Dr Tim Fenton: I have no competing interests concerning this topic.

Prof Anne Mackie: No conflicts.