New data from Denmark shows the HPV vaccine’s powerful long-term impact, while also revealing why cervical cancer screening is still essential.

A Danish study published in the journal Eurosurveillance reports that women who received the human papillomavirus vaccine in their adolescence are significantly less likely to develop human papillomavirus infections later in life.

Background

Prolonged infection with human papillomavirus (HPV) is associated with an increased risk of developing cervical cancer. Early screening and vaccination against HPV are effective strategies to prevent this cancer type.

Screening for precancerous lesions has been a widely considered strategy for secondary prevention of cervical cancer in Europe. Vaccines covering both high-risk and low-risk HPV types have been introduced as a primary preventive intervention at the end of the 2000s.

In Denmark, free public HPV vaccination (4-valent vaccine) was initially offered to all girls aged 13 to 15 in October 2008. It was later introduced to all girls turning 12 in January 2009. In November 2017, a 9-valent vaccine, which covers high-risk HPV types responsible for up to 90% of cervical cancers, was introduced in the country.

Cervical cancer screening is offered to women living in Denmark from the age of 23 years until the age of 64 years. One of the first groups of women who received the 4-valent HPV vaccination as teenage girls in 2008 reached the screening age of 23 years in 2017.

To carefully monitor screening outcomes in these vaccinated women, Trial23, a public health study embedded in the Danish national cervical screening program, was designed to determine the prevalence of HPV infection in cervical cell samples collected during three consecutive rounds of screening invitations.

In the current study, researchers assessed the prevalence of HPV infection in these consecutive cervical samples and the changes in HPV persistence and incidence between the first, second, and third samples.

Key findings

A total of 17,252 women with at least one cervical cell sample were registered in the Trial23 between February 2017 and February 2024. In this study, researchers analyzed 16,955 cervical samples collected from 8,659 women.

The prevalence of any high-risk HPV infection in the first, second, and third rounds of cervical samples was 32%, 28%, and 31%, respectively. The prevalence of HPV types 16 and 18 (high-risk viruses covered by the 4-valent HPV vaccine) remained low over time in all analyzed samples.

The comparison between vaccinated and unvaccinated women revealed significantly lower prevalence of HPV types 16 and 18 in vaccinated women. The prevalence of this virus type was 15 to 17% before vaccination, which reduced to less than 1% in vaccinated women by 2021.

Notably, the study found that about one-third of women still have infections with high-risk HPV that are not covered by the vaccine, and that the incidence of these infections was significantly higher in vaccinated women compared to unvaccinated women. However, the prevalence differences were not statistically significant.

Regarding HPV infection persistence and incidence, the study found a high persistence for both vaccine-covered and non-covered virus types, irrespective of vaccination status. The incidence of HPV types 16 and 18 was significantly lower in vaccinated women compared to that in unvaccinated women. However, the incidence, but not prevalence, of non-covered high-risk HPV types was significantly higher in vaccinated women compared to that in unvaccinated women, a pattern the authors suggest may be due to type replacement or unmasking.

Study significance

The study reports the prevalence of HPV infection in three sets of cervical cell samples collected consecutively from young Danish women who received the 4-valent HPV vaccination in their adolescence.

According to the findings, the prevalence of infection with HPV types 16 and 18 in vaccinated women is currently less than 1%, a significant drop from the pre-vaccination prevalence. In unvaccinated women, the prevalence is 5%, which is also much lower than the pre-vaccination prevalence. The drop in prevalence in unvaccinated women indicates population immunity.

Regarding infections with high-risk HPV types that are not covered by the vaccine, the study reports a prevalence of 30% in vaccinated women and 27% in unvaccinated women, which is a non-significant difference. A persistently high prevalence of non-vaccine high-risk HPV types in both vaccinated and unvaccinated women highlights the need for continuous screening of these generations until women vaccinated as girls with the 9-valent vaccine covering all major HPV types reach the screening age. At this point, the screening model might be reconsidered, with the study suggesting that less intensive but continued screening could be appropriate.

The study finds no significant differences in the persistence of HPV 16 and 18 infections between vaccinated and unvaccinated women, which indicates that the 4-valent vaccine, which covers high-risk HPV types 16 and 18 and low-risk types 6 and 11, is a prophylactic (preventive) vaccine and not a therapeutic vaccine. The conclusion supports the finding that persistence rates were similar regardless of vaccination status.

Overall, the study findings highlight the long-term protective efficacy of the HPV vaccine and advise close monitoring of factors associated with vaccine hesitancy and low vaccine coverage, such as perceived side effects of the vaccine.Journal reference:

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