HPV testing could be more accurate than smear tests for initial screening of cervical cancer

Wednesday July 4 2018

"Hundreds of women will be spared from cervical cancer every year when a new test replaces conventional screening," reports the Mail Online.

A study from Canada found that an initial test for human papilloma virus (HPV), which causes almost all cases of cervical cancer, led to the discovery of more pre-cancerous lesions than were found with conventional smear tests.

Smear tests look for changes to cells of the cervix, while HPV testing looks for the presence of the virus.

At present, the NHS screening programme for cervical cancer starts with a smear test. Women whose smear test results show possible low-grade or borderline changes to cells will have the sample tested for HPV. Those who have low-grade changes and HPV will then be referred for further tests (a colposcopy).

However, some areas of the NHS are testing a system where HPV tests are used first. If this is successful, the NHS may switch to initial HPV testing.

This study suggests this change would lead to more cases of pre-cancerous lesions being found than under the current system.

Where did the story come from?

The research came from doctors and scientists working on Canada's cervical screening programme, including researchers from the University of British Columbia, British Columbia Centre for Disease Control, Lower Mainland Laboratories, British Columbia Cancer and McGill University.

It was funded by the Canadian Institutes of Health Research and published in the peer-reviewed Journal of the American Medical Association on an open-access basis, so it is free to read online.

The coverage in the Mail Online was accurate but failed to explain that one possible risk of changing to the new system would be an increase in "false positive" results, where women with HPV but no cancerous changes are referred for further investigations.

What kind of research was this?

This was a randomised controlled trial looking at the results of the 2 systems of testing over the course of 48 months. This is usually the best way to compare tests and see which works best.

What did the research involve?

Researchers recruited 19,009 women to have initial screening either by HPV test or smear test, with around half randomly assigned to each group.

Women who tested negative for HPV were recalled after 48 months for both HPV and smear tests, while those who had a negative smear test were recalled after 24 months for a repeat smear test, then again at 48 months for both tests.

Women with positive HPV or smear tests had their samples immediately analysed using the other test and then had a colposcopy if results showed both HPV and changes to cells.

The smear tests were carried out using liquid-based cytology (the standard method used in the NHS). HPV testing was carried out by checking DNA samples. Women also filled out questionnaires about lifestyle and sexual health history to ensure differences in results were not down to imbalances between the test groups.

The women who took part in the study were aged between 25 and 65, had not had a smear test in the past 12 months, were not pregnant, and had no history of cervical cancer or pre-cancerous changes in the past 5 years.

Researchers compared results for the first round of testing with results at the end of the 48 months. They focused mainly on moderate or severe changes to cervical cells (pre-cancerous changes) that could lead to cervical cancer. The medical term for these types of changes is "cervical intraepithelial neoplasia grade 3 or above" (CIN3+).

What were the basic results?

In the first round of screening at the start of the study, more cases of CIN3+ were found in women who had HPV tests (7 per 1,000 women) than women who had smear tests (4.4 per 1,000 women).

However, 48 months after the start of the study, there were fewer cases of CIN3+ among women who had HPV tests than among smear tests, presumably because they had been found and treated in the first round of screening.

At the final 48-month screening there were:

  • 2.3 cases of CIN3+ per 1,000 women who initially had HPV tests (95% confidence interval [CI] 1.5 to 3.5)
  • 5.5 cases of CIN3+ per 1,000 women who initially had smear tests (95% CI 4.2 to 7.2)

Women who had a negative HPV test at the start of the study were much less likely to develop CIN3+ within 48 months than women who had a negative smear test at the start of the study.

The results showed:

  • 1.4 cases of CIN3+ per 1,000 women who had tested negative for HPV (95% CI 0.8 to 2.4)
  • 5.4 cases of CIN3+ per 1,000 women who had negative smear tests (95% CI 4.1 to 7.1)

More women were referred for colposcopy after HPV tests at the start of the study: 57 per 1,000 women compared with 30.8 per 1,000 women after smear tests – but the reverse was true at 48 months.

Total referrals for colposcopy were similar between the groups – 106.2 per 1,000 women for HPV testing and 101.5 per 1,000 women for smear testing.

How did the researchers interpret the results?

The researchers said their results show that "primary HPV testing detects cervical neoplasia earlier and more accurately than cytology", adding that it "detected significantly more CIN3+ and CIN2+ cases in the first round and significantly reduced CIN3+ and CIN2+ rates 48 months later".

They also cautioned that more work needs to be done to assess the economic consequences of changing the screening model.

Conclusion

While the results of the study are encouraging and suggest that HPV testing could work well as a primary test in place of cervical smears, we do not have longer-term results to show whether it actually makes a difference to how many women get invasive cervical cancer or die of the disease.

We therefore don't know whether the Mail Online's claim that "hundreds of women would be spared cancer" is necessarily true.

However, we do know that detecting cervical cancer earlier makes it easier to treat, so a test that can do that is likely to be welcome. What is unclear at the moment is whether it might result in more women needing further investigations, such as a colposcopy.

Girls and young women are now offered vaccination against HPV, but it will be some time before this prevents the majority of cases of cervical cancer. Women should continue to take part in cervical cancer screening, whether they have been vaccinated or not.

Find out more about the current NHS cervical cancer screening programme.

Analysis by Bazian
Edited by NHS Choices