18 June 2018

Study Examines First Birth Cohort to Receive HPV Vaccine: The Vaccine Works

HPV Vaccine

Girls in the first birth cohort to be offered and receive the HPV vaccine showed a lower degree of dysplasia which may eventually lead to cervical cancer than a birth cohort from 1983. This is the conclusion of a new study conducted by researchers at the University of Copenhagen, who have been the first to study the vaccine’s effect on the general population.

The effects of the HPV vaccine, which in 2009 became part of the Danish childhood vaccination programme, have been examined by researchers from the Faculty of Health and Medical Sciences at the University of Copenhagen. And the conclusion is unmistakable: The HPV vaccine works.

The new study, recently published in the scientific International Journal of Cancer, is the first to examine the effect of the vaccine in the population at large, say Professor Elsebeth Lynge and PhD student Lise Thamsborg from the Department of Public Health, University of Copenhagen.

‘It is the first study in the world to test the Gardasil-4 vaccine on a population level. The childhood vaccination programme, which includes the HPV vaccine, is targeted at the entire population. Therefore, it is important to look at the entire population and the effect of the vaccine after the first screening of women aged 23 years,’ says Professor Elsebeth Lynge, last author of the study.

Reduction in Severe Dysplasia
The researchers have looked at the 1993 birth cohort, which was the first birth cohort to be offered the vaccine. They have then compared it to a 1983 birth cohort, who have not been offered HPV-vaccination. The two birth cohorts of women are comparable and resemble each other as regards level of education and average age of sexual debut, among other things.

The researchers have then examined the results of the women’s first cervical screening test. The 1993 birth cohort was invited to a screening test in 2016, while women born in 1983 had their first screening test in 2006, before the vaccine was marketed. The researchers discovered a significantly reduced risk of severe dysplasia in the 1993 birth cohort compared to the 1983 birth cohort. To be precise, the risk was reduced by 40 percent.

‘This means that fewer women have to be referred to a gynaecologist for further examination and have a tissue sample taken. Eventually we also expect fewer to fall ill’, says Lise Thamsborg, first author of the study.

The girls from the 1993 birth cohort were 15 years old when they received the vaccine. And the researchers expect the effect to be even more pronounced today, where girls are offered the vaccine already at the age of 12.

‘It is better. We expect the effect to be greater among those vaccinated at the age of 12, because very few have been sexually active at this age’, says Lise Thamsborg.

A tissue sample from a cervix with severe dysplasia (HSIL).

New Technology Since 2006
However, the study did not only find a reduction in severe dysplasia. Contrary to expectation – and from what randomised trials have shown – the women born in 1993 showed a higher level of mild dysplasia than the women born in 1983.

In 2006, though, new technology was introduced for examining the cell samples that reveal cases of dysplasia. This may be the cause of the increase in cases of mild dysplasia, the researchers believe.

‘The new technology has led to fewer inadequate samples, and the samples are of a higher quality today. So the samples are more sensitive. This may be the cause’, says Lise Thamsborg.

The next step for the researchers is to examine the tissue samples taken from women with dysplasia. The aim is to learn whether and, if so, how cases of mild and severe dysplasia, respectively, have developed.

If a woman suffers from severe dysplasia, a tissue sample is taken. It can reveal precursor lesions to cervical cancer. There are different levels of these precursor lesions. If a woman shows mild dysplasia, she is invited to a control typically six months later to see whether the changes have stopped or developed further.

HPV, Vaccination and Screening:
*There are more than 100 different types of Human Papilloma Virus, also called HPV. 15 of these are known to be carcinogenic. 70 percent of all cases of cervical cancer are caused by the two HPV types HPV 16 and HPV 18.

*HPV vaccination is included in the Danish childhood vaccination programme and is recommended for girls aged 12 years. The vaccine was introduced after its effect had been proven in a randomised trial.

*Last fall a new HPV vaccine was introduced, Gardasil-9, which protects against nine types of HPV of which the seven are responsible for up to 90 percent of all cases of cervical cancer.

*The first vaccine, Gardasil-4, was used from 2009 to 2016 and is the vaccine given to the first birth cohort of girls born in 1993. From 2016 to the fall of 2017 the vaccine used was Cervarix. All three vaccines protect against HPV 16 and HPV 18.

*All women in Denmark aged 23-49 years are invited to a cervical screening test every three years. Women aged 50-59 years are offered a screening test every five years, and between the age of 60 and 64 an HPV test is conducted.

*Each year around 370 new cases of cervical cancer are discovered and around 100 women die as a result of the disease. Each year around 6,000 women are treated for precurser lesions with a so-called conization.

Source: Statens Serum Institut, the Danish Cancer Society.

The study has been published in the scientific International Journal of Cancer. It is funded by Kirsten and Freddy Johansen’s Foundation.

Scientific article:
‘Impact of HPV‐vaccination on outcome of cervical cytology screening in Denmark – a register based cohort study’.

Professor Elsebeth Lynge
Phone: +45 20421863
Email: elsebeth@sund.ku.dk

PhD Lise Thamsborg
Phone: +45 28919504
Email: lith@sund.ku.dk

Press officer Cecilie Krabbe
Phone: +45 93565911
Email: cecilie.krabbe@sund.ku.dk