How should screening for a disease be adapted for people with a considerably lower risk of developing the disease? Women in Denmark who were vaccinated as girls against human papillomavirus (HPV) are now eligible for their first cervical cancer screening. Since 2017, a research project has investigated how to adapt screening to ensure the early detection of precancerous lesions without leading to overdiagnosis or unnecessary treatment. The project also investigated whether other types of HPV, which the vaccine does not protect against, may present a future risk.
The women in Denmark who were HPV vaccinated as girls are now being invited to their first cervical cancer screening. But how should these women with a much lower risk of cancer because of the vaccination be screened? This question is central to a research project investigating how to optimally adapt screening to ensure the early detection of precancerous lesions and avoid overdiagnosis or unnecessary examinations.
“The study is part of a larger project that has been ongoing since 2017 investigating cervical cancer screening among HPV-vaccinated women and especially focusing on how to adapt screening methods to reflect the lower risk of cancer without resulting in overdiagnosis. We are also investigating whether other types of HPV that the vaccine does not cover could become a future risk. Our goal is to ensure a balance between early detection and minimising the burden on participating women,” explains Mette Hartmann Nonboe, PhD Fellow, Centre for Health Research, Zealand University Hospital, Nykøbing Falster, Denmark.
Hidden threat
HPV is a group of viruses that can lead to cervical cancer, especially types 16 and 18. These two types are associated with about 70% of cases of cervical cancer. Since HPV vaccination became part of the childhood vaccination programme in Denmark in 2009, the number of infections with these types of HPV has fallen dramatically.
“This generation of women is the first to have full access to vaccination, which makes it fascinating to analyse their real-life screening data and determine how effective vaccination is in reducing precancerous lesions of the cervix,” says Mette Hartmann Nonboe.
Although vaccination has proven to be highly effective, challenges remain. The researchers are now investigating whether other types of HPV not covered by the current vaccination may present a risk as a key component of the study.
“HPV16 and HPV18 are associated with almost 70% of the cases of cervical cancer. With the vaccination being effective, we now want to investigate whether other types are becoming a risk,” Mette Hartmann Nonboe explains.
Screening but not overdiagnosis
One dilemma of modern screening for cervical cancer is how to detect precancerous lesions early without overburdening the health system and individual women with unnecessary follow-up examinations. The HPV test is more sensitive than the traditional endocervical cell sampling, but the sensitivity can also lead to many women testing positive for transient HPV infections that the body can combat on its own.
“Many studies have been conducted on the risk vaccinated women face, but they are based on limited cohorts. This study provides a broader picture and enables us to rethink our screening programme,” explains Mette Hartmann Nonboe.
The researchers found that 35% of the women tested in the study were HPV positive, but few had types 16 and 18. The result shows that the vaccination works, but it also raises the question of how to optimally treat women who test positive for other types of HPV.
“Many women younger than 30 years have positive HPV test results – up to 35% – but only a few have type 16 or 18. So the vaccination works, but we must avoid overburdening the individual women and the system with unnecessary examinations,” adds Mette Hartmann Nonboe.
Adjusting to a new normal
The great success of HPV vaccination poses the question: should vaccinated women be screened as often as unvaccinated women? Or can the number of screenings be reduced and the efforts be more targeted?
“Examining how to adapt the screening is crucial, since vaccinated women have a much lower risk. This may mean screening less often or differently,” says Mette Hartmann Nonboe.
The World Health Organization recommends HPV testing for unvaccinated women older than 30 years.
“We may need to rethink this approach for vaccinated women,” Mette Hartmann Nonboe notes.
Trailblazing success – but what next?
The HPV vaccination has profoundly affected public health in Denmark. In fact, the incidence of cervical cancer is now so low for women younger than 30 years old that Denmark is approaching the WHO definition of elimination.
“The vaccination is a great success. The incidence of cervical cancer in Denmark is now down to 3 cases per 100,000 women for women younger than 30 years, which is below the WHO threshold for elimination,” explains Mette Hartmann Nonboe.
This testifies to the effectiveness of both the vaccination programme and the changes to the screening programme over the years. However, much remains to be done.
“We still seek to understand how vaccinated women fare over time and what happens to women infected with the other types of HPV. This will enable us to adjust the screening programme further,” concludes Mette Hartmann Nonboe.
“Screening outcome of HPV-vaccinated women: data from the Danish Trial23 cohort study” has been published in PLoS One. The Novo Nordisk Foundation supported the research.
