Women who have received HPV vaccine may require fewer cervical screening tests

“HPV vaccinated women 'will only need three smear tests',” BBC News reports. This follows a new UK study that aimed to determine how often women who had been vaccinated against the human papillomavirus (HPV) should have cervical screening.

In 2008 the NHS introduced the HPV vaccination programme for girls aged 12-13 to vaccinate against the "16th" and "18th" strains of the virus. These strains account for most cases of cervical cancer. The first girls to be vaccinated are now approaching 25, the age at which cervical screening starts in England.

Researchers wanted to see if current guidelines regarding screening should be amended in the future to take account of the benefits of the vaccine and recent advances in screening methods. Currently cervical screening is recommended every three years for women aged 25-49 and every five years for those aged 50-64.

Using a simulated model, researchers predicted that new cervical screening test methods (which directly check for HPV rather than just for abnormal cells) could mean women vaccinated against HPV 16/18 only need three cervical screening tests in their lifetime, and women vaccinated against wider HPV strains only need two.

They also predicted that using the new test methods, women who haven’t been vaccinated may only need to have seven screening tests in their lifetime. This is about half as many they are currently offered.

It’s important to remember that these findings are estimates based on simulated data. While the data is certainly useful, and may feed into the development of amended guidelines, it doesn’t change current cervical screening advice .

Where did the story come from?

The study was carried out by a team of researchers from the Centre for Cancer Prevention at Barts and The London School of Medicine and was funded by grants from Cancer Research UK and the Engineering and Physical Sciences Research Council.

The study was published in the peer-reviewed International Journal of Cancer on an open access basis and can be read for free online.

Generally, the UK media’s coverage on this study was balanced and accurate.

What kind of research was this?

This was a modelling study which used published data to determine the appropriate frequency of screening for cervical cancer in women who had been vaccinated against HPV.

They simulated different scenarios according to vaccine efficacy and the HPV strains covered by the vaccine.

They also wanted to see whether new cervical screening methods could make a difference. Samples are normally examined to see whether any cells look abnormal and show potentially cancerous changes. A trial in 2014 found a new method may be better, which instead tests the samples for HPV (called primary HPV testing).

Modelling studies such as this are increasingly being used to inform health policy decisions. Especially in situations when real-world data could take several years, or even decades, to emerge.

Although they can be incredibly useful for giving an idea of potential future scenarios, it’s important to bear in mind that these are not real life and may not be fully accurate.

What did the research involve?

The researchers created a model based on the concept that there was no HPV vaccine. The results of this first model were then used as a benchmark for the model described below.

Using HPV prevalence data from the ARTISTIC trial in England, they looked at the likelihood of transitions between health or disease states at six-month intervals from the ages of 12 to 80. The probabilities were age-dependent.

The following assumptions were made:

• everyone was HPV negative at the start
• cervical cancer cannot occur without HPV infection
• no new HPV infections occurred after the age of 65
• no one died before the age of 80

The disease states included progressing from having persistent HPV, to different severities of abnormal cell change, to asymptomatic cancers (that would only be diagnosed as a result of screening) to symptomatic cancer that would be diagnosed without screening.

The researchers then looked at the effect of five vaccine scenarios. One assumed 100% efficacy against HPV 16/18, others assumed different levels of cross-protection against other strains, and one assumed 100% protection against 16/18 and five additional HPV strains.

They looked at the effect of 100% screening programme attendance, then looked at screening attendance rates in England to gain a more realistic scenario. They also looked at the effect of switching to primary HPV testing (where a cervical cell sample is directly tested for the presence of HPV, rather than a more general analysis to check for abnormal cells).

The researchers compared the number of cancers that would be diagnosed using the vaccination/screening scenarios with the number of symptomatic cancers that would be found in the absence of screening or vaccination.

Using these numbers, they calculated the proportion of cancers prevented by the combination of vaccination and screening.

What were the basic results?

Overall with no screening and no vaccination, a woman’s overall lifetime risk of cervical cancer was set at 2%.

The model found the following:

• The HPV 16/17 vaccine prevented 70.3% of cancers (95% cumulative risk [CR]: 65.1-75.5) even if women attended no subsequent screening. As expected, vaccines with assumed cross protection or covering more strains gave greater protection.
• Comparatively, screening alone – without vaccination – prevented 64.3% of cancers (95% confidence interval (CI): 61.3-66.8). This was assuming realistic compliance to the UK screening programme.
• If switching to HPV primary testing of cell samples, the screening interval could be doubled for unvaccinated women, with no loss in cancer protection. These unvaccinated women would then require seven lifetime screens.
• If vaccinated women attended screening they gained greater cancer protection. There was additional protection if women vaccinated against HPV 16/18 attended three lifetime screens. There was no meaningful benefit from adding a fourth screen (1.3% increased cancer protection, 95% CR: -0.3% to +2.8%).
• Women who have been vaccinated against HPV 16/18 plus five additional strains (this type of HPV vaccine is currently not available on the NHS) would require two lifetime screens according to the model.

How did the researchers interpret the results?

The researchers concluded: “Our analyses clearly demonstrate that many fewer lifetime screens are necessary for vaccinated women to have the same level of protection against cervical cancer as is currently provided by 3- and 5-yearly cytology screening in unvaccinated women.”

Conclusion

This informative modelling study used published data to estimate the appropriate frequency of cervical screening for women who have been vaccinated against HPV.

The research suggests that if newer HPV testing is more effective than the standard cervical screening test that looks for abnormal cells, this could also benefit women who haven’t been vaccinated against HPV. With the new type of test, these women may only need half as many cervical screening tests as they are currently offered in their lifetime.

Women vaccinated against the 16/18 strains of HPV could gain maximum cancer protection with only three cervical screening tests in their lifetime, while women vaccinated against strains 31/33/45/52/58 in addition to HPV 16/18 could gain maximum protection with just two screening tests in their lifetime.

The researchers suggest the cervical screening programme should be tailored for vaccinated and unvaccinated women. This would mean recording vaccination status and then linking this with the screening programme database.

However, while this study presents valuable estimates, this is only simulated data. This will need to be considered alongside further research and ongoing data collection from the screening programme.

For now, the cervical screening programme in the UK remains unchanged. All women who are registered with a GP are invited for cervical screening:

• aged 25 to 49 – every 3 years
• aged 50 to 64 – every 5 years
• over 65 – only women who haven't been screened since age 50 or those who have recently had abnormal tests

All girls can get the HPV (human papillomavirus) Gardasil type of vaccine free (which protects against the 16/18 strains, as well as two other strains that can cause genital warts) from the NHS from the age of 12 up to their 18th birthday.