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Can a single injection prevent cervical cancer?

Tuesday 11 February 2020

"Cervical cancer could be prevented with a single injection," reports The Independent. This is based on a study that looked at the impact of different numbers of doses of human papillomavirus (HPV) vaccination in more than 130,000 women in the US.

At present, young people in the UK are offered 2 doses of the HPV vaccine to help protect against cancers caused by HPV, including cervical cancer. The first dose is given in school Year 8 (at ages 12-13 years), and the second dose 6 to 12 months later.

This large US study found that women who had 1, 2, or 3 or more doses of the HPV vaccine between the ages of 15 and 19 years old had similar reductions in their risk of developing pre-cancerous changes in the cervix over the next 5 years, compared with women who were not vaccinated.

However, this study had several limitations. It did not randomly allocate women to different doses of the vaccine. It relied on existing data, which means factors other than the number of vaccination doses received could have influenced the results.

Because of these limitations we cannot conclude from this study that a single dose would be as effective as 2 doses for reducing cervical cancer risk in the UK population. For now the advice remains that 2 doses of the vaccine offers the best protection.

Find out more about the HPV vaccine in the UK.

Where did the story come from?

The study was carried out by researchers from the University of Texas Medical Branch, Yale School of Medicine, and Baylor College of Medicine, all in the US.

It was funded by the Institute for Translational Sciences at the University of Texas Medical Branch, which receives funding from the US National Institutes of Health. Some of the researchers also received funding from the Cancer Prevention Research Institute of Texas.

The study was published in the peer-reviewed medical journal Cancer.

Both the Daily Express and The Independent report the basic results of the study accurately but interpret these differently.

The Independent reports that the results show "a single [dose] of the vaccine is as effective as multiple doses". The Daily Express reports "a single [dose] has been shown to be more effective than having two or three injections".

The interpretation by the Daily Express is not correct. The study did not statistically compare these different doses, so we cannot rule out the small differences between the groups occurring by chance.

What kind of research was this?

This was a retrospective cohort study. The researchers used routinely collected data to look at whether the number of doses of HPV vaccine a woman had was linked to her risk of developing pre-cancerous changes to her cervix.

This type of study takes advantage of existing data to look for links between different events. While this is a quick way to ask this question, it has limitations.

The main limitation is that women who received different numbers of doses of the HPV vaccine may also differ in other ways. These differences may also affect the women's risk of developing pre-cancerous changes to her cervix. While the researchers did take steps to minimise the effect of these differences, factors other than the number of doses of HPV vaccine may still have had an impact on their findings.

What did the research involve?

The researchers used a large US health insurance database to identify women aged 9 to 26 years old, who had received at least 1 dose of the HPV vaccine and had a smear test at least 1 year after their final dose.

They matched each of these women with a similar woman who had not had the vaccine but did have a smear. They then compared the results to see whether women who had different numbers of doses of the vaccination were less likely to have developed pre-cancerous changes to their cervix.

The researchers identified records for 66,541 eligible women in the database who had been vaccinated with the vaccine that protects against 4 different strains of HPV between 2006 and 2015 (the type of vaccine used in the UK).

They matched each woman to a "control" – a woman in the database who had not been vaccinated but lived in the same region of the US, was of a similar age, had a similar number of pregnancies and a similar history of sexually transmitted infections before the date of first vaccination.

Only women who had a smear test at least a year after their final HPV vaccination were included. Women who had smears, HPV tests, and abnormal or cancerous cervical cells less than 12 months after their final dose of HPV vaccine were excluded from the study. This aimed to remove women who may have already had HPV infection before their vaccination.

On the smear test results, the researchers were looking for changes to the cells of the cervix that can be early signs of cancer. There are different levels of severity of these changes, the main one that researchers were looking for was "pre-invasive cervical disease". This means that the cells are abnormal and could become early stage cancer, but have not started to invade beneath the outer surface of the cervix.

The researchers looked at results of smear tests taken up to 5 years after the women had their vaccination. They compared women who had 1, 2, or 3 or more doses of the HPV vaccine with their unvaccinated counterparts. They also looked at whether results differed depending on the age at which the women had their first dose of the vaccine. They adjusted results for region where the women lived, and history of pregnancy and sexually transmitted infection.

What were the basic results?

More than half of the women who were vaccinated had 3 or more doses (58%), and almost all had their first dose at age 15 or older (91%).

Among women who had their first dose of vaccine between the ages of 15 and 19, having any dose (1, 2, or 3 or more doses) of the HPV vaccine was linked with a reduced risk of having pre-invasive cervical disease, compared to not having the vaccination.

Women who were not vaccinated had a 2.65% chance of having pre-invasive cervical disease over 5 years of follow-up. This compared with a 1.62% chance for those who had 1 dose of HPV vaccine, 1.99% for those who had 2 doses, and 1.86% for those who had 3 doses. This represented:

  • a 36% reduction in risk in those who had 1 dose (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.47 to 0.88)
  • a 28% reduction in risk in those who had 2 doses (HR 0.72, 95% CI 0.54 to 0.95)
  • a 34% reduction in risk in those who had 3 doses (HR 0.66, 95% CI 0.55 to 0.80)

Among women who had their first dose of vaccine aged 20 or older there was not a significant link between vaccination and pre-invasive cervical disease risk. This may be because these women were already sexually active before having the vaccination, and may have already contracted HPV.

There was a trend among women who had their first vaccination before the age of 15 for reduced risk of pre-invasive cervical disease, compared to women who were not vaccinated. However, as relatively few women in this study had their first vaccination at this age, and pre-invasive cervical disease is uncommon in younger women, this analysis was not conclusive.

How did the researchers interpret the results?

The researchers concluded that receiving 1, 2, or 3 doses of HPV vaccine in women aged 15 to 19 is linked with a reduced risk of pre-invasive cervical disease compared to not being vaccinated. They say that the results showed a "similar degree of association between varying doses of [the HPV] vaccines and pre-invasive cervical lesions" in this age group.


While this study is useful in giving a picture of the likely impact of HPV vaccination in the US, it is limited in what it can tell us about the ideal number of doses of HPV vaccine.

The main concern is that the observational nature of the study means that other factors could be contributing to the outcomes of the different groups. A randomised controlled trial would ideally be needed to determine the effect of different numbers of doses of the vaccine.

As with all studies that rely on previously collected data, there are other limitations. This includes the potential for details to be misrecorded in the database, the fact that information the researchers would like to have may not be recorded, and that information may not be complete.

For example, the study relied on women deciding to go for smear tests (less than a third of women did so) and also claiming on their health insurance for the test. We do not know what happened to the women who did not choose to go, or women who may not have claimed for smear tests.

The results from this private health insurance database may also not be representative of all women in the US. Poorer women and those from some ethnic minorities are likely to be under-represented. Unfortunately the database did not include information on women's socioeconomic status or race, so this could not be checked.

The women in this study were relatively young (average age about 18-19 years at first vaccination) and follow-up was only for 5 years after last vaccination. As cervical cancer can take years to develop, rates of the illness were likely to be very low in this group, which is why the study only looked at pre-cancerous changes. Longer-term follow-up would be needed to look at cervical cancer rates.

This US sample also may not be similar enough to the population that is vaccinated against HPV in the UK for the findings to be extended to the UK. In the UK, both boys and girls are currently offered vaccination against HPV, starting before age 15.

Overall, the findings are interesting, but by themselves are not enough to suggest that a change is needed in how many doses of HPV vaccinations are given in the UK.

Find out more about the HPV vaccine.

Analysis by Bazian
Edited by NHS Website