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24th November 2023
Vaccination against human papillomavirus (HPV) appears to have changed the mix of HPV strains in circulation, say researchers who have spotted the ‘strain replacement’ for the first time.
An analysis of data from 60,000 young women in Finland who took part in a trial of the HPV vaccine where different cities adopted different approaches also found a decrease in more strains of the virus where girls and boys were both vaccinated.
Four years after vaccination, they found that the vaccine had markedly depleted targeted cancer-causing HPV types in the girls-only vaccine groups as well as the communities where boys and girls had been immunised.
Where boys and girls were vaccinated, there was also an increase of HPV types with lower cancer risks filling the gap left by the cancer-causing vaccine targeted strains around four to eight years after the vaccine was given.
The findings raise questions over potential changes to cervical cancer screening programmes in the future but UK experts said it was too soon to come to any conclusion.
Writing in the journal Cell Host and Microbe, the team said the diversity of strains found were similar to communities where no vaccination had been done, only without the cancer-causing strains targeted by the vaccine.
Study leader Dr Ville Pimenoff, an evolutionary biologist from the Karolinska Institute, Sweden, and University of Oulu, Finland said: ‘HPV vaccine is effective to clear most cancer-causing HPVs, and what we have observed here is the subsequent new equilibrium of untargeted HPV types interacting with the host communities.’
He added: ‘Importantly, the increase of vaccine-untargeted low-cancer-risk HPVs do not increase the risk of cancer.’
The researchers suggested that the findings could lead to the redesign of HPV screening approaches for cervical cancer prevention, which include testing for HPVs with lower cancer risks.
With the increase of low-cancer-risk HPV types in the vaccinated population, ‘current screening is likely to result in over-diagnosing individuals who are not at risk, he added. ‘That would be a huge burden for the healthcare system.’
Professor Anne Mackie, director of the UK National Screening Committee said the study was very welcome but more research was needed and the committee has commissioned a modelling study to help understand the likely impact of potential alternative screening strategies on the vaccinated cohort in the future.
She said: ‘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.’
Professor Stephen Duffy, professor of cancer screening at Queen Mary University of London said a major finding from the research was that immunising both boys and girls is the best policy.
‘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.’
This comes as NHS England announced plans to eliminate cervical cancer by 2040 through increasing uptake of the HPV vaccine and cervical screening.
As part of a new vaccination drive, NHS England will support health and care professionals to identify patients in most need of the HPV vaccine via ‘targeted outreach’ and offering jabs in convenient local places such as libraries and community centres.
The NHS App will undergo expansion so that people can view their full vaccine record and book appointments in a ‘new dedicated space’ – currently only Covid and flu vaccination status is visible, but this will be increased to all 15 routine vaccine-preventable diseases, including HPV.
The NHS will also look to boost cervical screening by trialling ‘self-sampling’ to see if it could become part of national screening.
Last year, over five million people aged 25 to 64 were invited for screening, which NHS England said is ‘more…than ever before’.
NHSE’s national director for vaccinations and screening Steve Russell said vaccination and screening are ‘some of the most powerful tools’ for preventing disease.
‘We have learnt invaluable lessons from the pandemic, with our hugely successful Covid-19 vaccine programme saving thousands of lives, and our vision for the future of vaccination draws on those learnings, with plans to educate millions more people on the importance of vaccination, while making it easier than ever before to access vaccines online,’ he added.
NHS Providers’ director of policy and strategy Miriam Deakin said they ‘welcome’ the pledge and ‘innovative strategies’ that demonstrate a ‘forward-thinking approach to healthcare’.
She said: ‘These measures not only aim to improve accessibility but also ensure that health services are more responsive to the needs of diverse communities.
‘Ensuring healthcare staff have the resources and training needed to effectively implement these plans is crucial for success.
‘A focus on education and increasing public awareness about the importance of HPV vaccination and regular cervical screening is also vital.’
According to the World Health Organization, cervical cancer is considered to be eliminated when its incidence rate is lower than four per 100,000 women.
Versions of this story were originally published by our sister publication Pulse.
25th September 2023
Cancer screening is designed to detect the presence of disease at an early stage, but whether it actually has the desired effect of reducing mortality is up for debate. Clinical writer Rod Tucker investigates.
In medicine, screening is designed to identify the presence of a disease in healthy individuals who are not displaying any of the typical clinical signs or symptoms of a particular condition. Cancer screening, for instance, can therefore be considered to serve a dual purpose: on the one hand it is preventative, but it can also enable the early identification of cancer or precursor lesions and thus having the potential to improve prognosis.
Cancer screening is already well established for breast, prostate, lung, cervical and colorectal cancers, and many of the current tests are very accurate. For example, one novel prostate cancer screening test has an accuracy of 94%.
The fact that cancer screening has the potential to reduce cancer-related mortality and ultimately improve lifespan, has been the main focus in public health messaging. In the past, such messaging has been emotive, employing powerful and persuasive tools such as fear and guilt, engendering a sense of personal responsibility and convincing individuals to be screened.
And this approach has clearly worked. For instance, in a survey of 500 individuals that included women over 40 years of age and men over 50 years, without a history of cancer, the majority (87%) believed that routine cancer screening was almost always a good idea. In addition, 74% felt that finding a cancer early, through methods such as screening, saved lives most or all the time.
But does cancer screening actually extend lifetime? Five-year survival is often presented to the public as evidence of the value of early detection, but one analysis concluded that changes in five-year survival over time bear little relationship to changes in cancer mortality.
A recent meta-analysis attempted to shed further light on the relationship between cancer screening and all-cause mortality, which offered some surprising results.
Most randomised controlled trials of cancer screening focus on disease-specific mortality as the outcome of interest. However, the validity of this outcome is highly dependant on an accurate ascertainment of death, which is not always clear.
This was highlighted in an analysis of 12 published randomised trials of cancer screening for which disease-specific and all-cause mortality data were available. The researchers identified major inconsistencies in both disease-specific and all-cause mortality but concluded that since all-cause mortality is not affected by bias in classifying the cause of death, it should be used as the main outcome of interest for randomised trials looking at cancer screening.
The most recent study to examine of the impact of cancer screening on all-cause mortality was conducted by a team based at the Institute of Health and Society, which is part of the University of Oslo in Sweden. The researchers performed a systematic review and meta-analysis of randomised clinical trials that reported on all-cause mortality to estimate the potential lifetime gained for six commonly used cancer screening tests when compared to no screening.
They focused on mammography screening for breast cancer; colonoscopy, sigmoidoscopy or faecal occult blood testing (FOBT) for colorectal cancer; computed tomography screening for lung cancer in smokers and former smokers; and prostate-specific antigen (PSA) testing for prostate cancer.
The team included trials with 10 to 15 years of follow-up and set the primary outcome of interest as lifetime in the screened group compared to the non-screening group based on all-cause mortality. Using these differences, the researchers calculated the absolute lifetime gained in days.
With the inclusion of just over 2.1 million individuals in the analysis for the six different cancer screening trials, the only screening test with a significant lifetime gain of 110 days (95% CI 0 – 274) was sigmoidoscopy. However, the lower 95% confidence interval extended to zero, so the effect was just significant.
Although there were gains in lifetime accrued for prostate (37 days) and lung (107 days) cancer screening, these increases were not significant.
Despite these largely negative findings, the researchers were quick to point out that they did not actually favour abandoning screening, merely that the current evidence did not substantiate the claim that common cancer screening tests saved lives by extending lifetime.
Although all-cause mortality has been suggested as a better study endpoint, a problem with using this metric is that the impact of screening on all-cause mortality, depends largely on the level of underlying risk of death from different causes, such as heart disease, within the population being screened.
Consequently, while there are clearly some limitations from focusing solely on cancer-related deaths as an outcome, this may be preferable with the caveat that deaths from other causes are carefully reviewed to identify potential cases of harm.
Nonetheless, a 2015 analysis concluded that currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon and either very rare or non-existent for all-cause mortality.
The use of all-cause mortality as a primary outcome may be more relevant for the multi-cancer early detection test, especially if deaths from the cancers targeted constitute a high proportion of expected deaths in the population recruited.
Perhaps the most important message from the recent cancer screening analysis is that in their discussions with patients, clinicians should no longer predicate the rationale for screening on the claim that it will both save lives and increase life expectancy. This may not always be the case.
11th July 2022
Cancer screening for breast, colorectal and cervical cancers was significantly reduced during the period of the pandemic compared to pre-pandemic levels according to the results of a systematic review by a group of Italian and US researchers.
According to GLOBOCAN in 2020 there were an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths and that cancer screening has contributed to a decrease in both cancer morbidity and mortality. As a result, any reduction in screening could potentially lead to a surge in cases. In fact, modelling studies have already indicated a possibly large increase in cases due to the pandemic.
Moreover, in a UK-based modelling study, the authors estimated that as a consequence of the pandemic, there would be a 7·9-9·6% increase in the number of deaths due to breast cancer up to year 5 after diagnosis and for colorectal cancer a 15·3 – 16·6% increase in additional deaths.
However, because of differences in the start date and duration of lockdown measures across the world, for the present study, the researchers wanted to examine how this variation impacted on screening. They focused on breast, colorectal and cervical cancer screening since the beginning of the pandemic and made a comparison with pre-pandemic levels.
The team searched all the major databases for observational studies and articles that reported data from cancer registries and which compared the level of screening tests performed before and during the pandemic and in different areas of the world.
Cancer screening reductions during the pandemic
A total of 39 articles were identified and included in the analysis with 21 related to breast, 22 colorectal and 11 for cervical cancers.
For the period between January and October 2020, there was an overall 46.7% (95% CI -55.5% to -37.8%) decrease in breast cancer screening in comparison the pre-pandemic level.
For colorectal cancer, the overall reduction was 44.9% (95% CI -53.8% to -36.1%) and this included a 52.5% reduction in colonoscopy, a 37.8% decrease in faecal occult blood testing and a 37.8% decrease in immuno-chemical testing.
With cervical cancer, the overall reduction was -51.8% (95% CI -64.7% to -38.9%).
Commenting on their findings, the authors noted that these reductions in screening occurred across the world but that there were some obvious differences. For example, Europe saw the largest reduction in mammography compared to North America. although the decrease for both colorectal and cervical cancer screening was similar in both areas.
The authors suggested that the most likely explanation for the reduced screening was the ‘stay at home’ order introduced during the early stages of the pandemic.
They concluded that there was a large reduction in cancer screening as a consequence of the COVID-19 pandemic and which could be associated with an increased number of deaths and called for further work to investigate the relationship between cancer diagnosis and treatment during the pandemic.
Citation
Teglia F et al. Global Association of COVID-19 Pandemic Measures With Cancer Screening: A Systematic Review and Meta-analysis JAMA Oncol 2022
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