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Success of HPV vaccine could lead to end of cervical cancer

Thursday 27 June 2019

"HPV vaccine programme in schools 'could wipe out cervical cancer for good'," reports the Mail Online.

Researchers in Canada summarised 65 studies from 14 countries that have introduced HPV vaccination since it became available a decade ago. The vaccine targets several strains of human papilloma virus (HPV), including strains 16 and 18 which cause most cervical cancers. HPV can also cause genital warts and some other types of cancer.

Researchers compared infection rates before and after introduction of the vaccine for both teens (13 to 19 years) and young adults (20 to 24 years). HPV 16 or 18 infections fell by 83% for teenage girls and 66% for young women 5 to 8 years after vaccine introduction.

Genital wart diagnoses fell for both teenage girls and boys and young men and women. The numbers of teenage girls and young women with pre-cancerous cells found in the cervix also fell 5 to 9 years after the vaccine was introduced – a good sign, as this suggests the vaccine really will reduce the number of women getting cervical cancer.

In the UK, girls aged 12 to 13 are offered the first dose of the vaccine at school, with a second dose 6 to 12 months later. Boys aged 12 to 13 will be offered the vaccine from September this year.

The researchers found that the greatest benefits of vaccination were seen in countries where more than 50% of the targeted population was vaccinated, and where girls were offered vaccination at multiple ages, to catch up on the older girls who had missed the introduction of the vaccine.

If vaccination programmes can lead to the eradication of HPV, in the same way that they did for smallpox, then this should result in a subsequent eradication of cervical cancer.

Find out more about HPV vaccination.

Where did the story come from?

The researchers who carried out the study were from the Université Laval in Canada. The study was funded by the World Health Organization, Fonds de recherche du Québec – Santé and the Canadian Institutes of Health Research. It was published in the peer-reviewed Lancet medical journal.

The study was widely and enthusiastically covered in the UK media. Most reports included comments from the researchers that cervical cancer could be eliminated within decades.

However, while the signs are hopeful, we cannot tell that at this stage.

What kind of research was this?

This was a systematic review and meta-analysis of population-level studies assessing the impact of introducing the HPV vaccine.

Systematic reviews are the best way to get an overview of the state of research looking at a topic, and a meta-analysis allows researchers to pool data to get an overall indication of the potential size of the effect from the evidence available. However, these reviews are only as good as the studies that are available to include.

What did the research involve?

The researchers updated a previous systematic review and meta-analysis they published in 2015. They searched for studies published since their last review, between 2014 and 2018, which had information about the introduction of routine HPV vaccination of girls. Studies needed to report on at least 1 of 3 results:

  • levels of HPV infection before and after the vaccination programme was introduced among girls and women
  • levels of diagnoses of anal and genital warts before and after the vaccination programme, among girls, boys, women and men
  • levels of girls or women found to have abnormal, pre-cancerous cervical cells (called cervical intraepithelial neoplasia, CIN) when screened, before, and after the vaccination programme

CIN is graded from 1 to 3 depending on how deep the abnormal cells go and how likely they are to develop into cancer. The researchers specifically looked at CIN grade 2 or higher.

The researchers looked at the possible impact of vaccination in 2 time frames: 1 to 4 years after vaccination and 5 to 8 years after vaccination (5 to 9 years for abnormal cervical cells).

They compared countries with high (50% or over) levels of vaccine coverage, or coverage of multiple ages, with those who had lower levels of vaccine coverage or who introduced the vaccine for 1 age group only.

What were the basic results?

HPV infections

Researchers found 23 studies looking at HPV infection.

HPV infections fell among girls and young women after the introduction of vaccination, compared with before.

  • among girls aged 13 to 19, infections with HPV 16 and 18 (types targeted by the vaccine most likely to cause cervical cancer) were down 70% 1 to 4 years after vaccine introduction (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.21 to 0.43) and down 83% at 5 to 8 years (RR 0.17, 95% CI 0.11 to 0.25)
  • among women aged 20 to 24, HPV 16 and 18 infections were down 37% at 1 to 4 years (RR 0.63, 95% CI 0.53 to 0.76) and down 66% at 5 to 8 years (RR 0.34, 95% CI 0.23 to 0.49)

Falls in the number of HPV infections among women aged 25 to 29 years (who were less likely to have been vaccinated) were smaller or non-existent, as were infections with types of HPV not covered by the vaccine.

Genital warts

Researchers found 29 studies about genital warts. Rates of genital wart diagnoses fell among girls, boys, young women and men after vaccination programmes were introduced. Boys may have been protected because of the reduced HPV infections among girls. Researchers found, 5 to 8 years after programmes began:

  • rates among girls aged 15 to 19 fell by 67% (RR 0.33, 95% CI 0.24 to 0.46)
  • rates among women aged 20 to 24 fell by 54% (RR 0.46, 95% CI 0.36 to 0.60)
  • rates among boys aged 15 to 19 fell by 48% (RR 0.52, 95% CI 0.37 to 0.75)
  • rates among men aged 20 to 24 fell by 32% (RR 0.68, 95% CI 0.47 to 0.98)

There was also a 31% reduction for women aged 25 to 29, but no effect for men of this age, or for women and men in their 30s who were unlikely to have been vaccinated.

Pre-cancerous cells

Researchers found 13 studies looking at rates of girls or women found to have abnormal cells that could lead to cervical cancer (CIN grade 2+) during cervical screening. They only looked at rates among screened girls or women. They found, 5 to 9 years after HPV vaccination began:

  • rates of CIN2+ among girls aged 15 to 19 fell by 51% (RR 0.49, 95% CI 0.42 to 0.58)
  • rates of CIN2+ among women aged 20 to 24 fell by 31% (RR 0.69, 95% CI 0.57 to 0.84)

However, rates rose among older women aged 25 to 29, who were unlikely to have been vaccinated.

Different vaccination regimes

When researchers looked at subgroups, they found those countries that had low vaccination coverage, or which began by vaccinating a single age group, had smaller reductions in all 3 HPV-related results.

How did the researchers interpret the results?

The researchers say their results show "a significant and substantial impact of HPV vaccination" on HPV infection, genital warts and CIN2+ rates "in the first 9 years after the start of HPV vaccination".

They said the study was "the first to show the real-world additional benefit of multi-cohort HPV vaccination and high routine vaccination coverage" and that these findings reinforced the WHO guidance to vaccinate girls at multiple ages from 9 to 14, when vaccination is first introduced into a country.

Conclusion

These are encouraging results that show the importance of girls having the HPV vaccination when it is offered. The reduction in rates of HPV 16 and 18 infection among girls and women, and the rates of abnormal pre-cancerous cells on cervical screening show that the vaccine is likely to be effective in its primary aim of reducing the numbers of cervical cancers.

The review has a few limitations. This type of before-and-after study does not automatically prove that the introduction of screening is the reason for the fall in HPV infections, genital warts and abnormal cells. For example, it could also reflect society changes, such as improved awareness and safer sex practices. The review was not able to take account of all of these possible contributing factors. However, the strength of the results across all outcomes, the lack of change for non-vaccinated HPV strains, combined with the increasingly strong effects over time and in countries with higher levels of vaccination coverage strongly suggest that vaccination is the main cause.

Does the vaccine spell the end of cervical cancer? The results suggest it might be possible, but of course it would depend on a high level of vaccine coverage. While it may be possible in high-income countries like those included in the study, it may be more of a challenge for lower income countries.

The vaccine being used for HPV in the UK protects against 4 types of HPV: 6, 11, 16 and 18. Between them, they account for the viruses that cause 70% of cervical cancers in the UK and 90% of genital warts. Girls and boys who have these vaccines should therefore have a much lower risk of cervical cancer and genital warts, as well as other types of cancer (including of the vulva, vagina, penis and anus) in future. Most women older than 25 years will not have been vaccinated against HPV and it's too late to vaccinate someone once they've already been exposed to the virus.

However, regardless of whether or not you've been vaccinated, taking part in cervical screening programmes is still very important for all women aged 25 to 64 to protect themselves against cervical cancer. The earlier abnormal cells are detected, the more likely they are to be successfully treated.

Find out more about ways to protect yourself against cervical cancer.

Analysis by Bazian
Edited by NHS Website