HPV testing followed by smear could improve cervical screening

British Journal of Cancer

Testing for the human papillomavirus (HPV) – a virus most women will encounter at some point in their lives – followed by a smear test if they are HPV positive, provides the most effective approach for cervical screening, new research shows today (Wednesday).

The study, published in the British Journal of Cancer*, gave around 26,000 women both smear and HPV tests to determine how best to use HPV testing for cervical screening.

Up to 8 out of 10 people in the UK will be infected with the HPV virus at some point in their lives.

Previous studies have shown that HPV testing could be more effective at picking up women with severe cervical cell changes, but there have been some outstanding questions about how an HPV based programme should be implemented. For example, it has been unclear how best to manage women with positive results from an HPV test.

Having carried out these tests, researchers looked at how likely women with different combinations of test results were to have severe cervical cell changes – known as CIN3.

They concluded that using HPV testing as the first line screening test, as well as smear testing for women who received a positive HPV result, could improve the performance of an HPV test for cervical screening.

Using this combination approach would mean that only women with the highest risks of having CIN3 were referred for further tests - reducing unnecessary examinations and picking up more serious cervical cell changes.
 
Dr Chris Meijer, study author based at the VU University Medical Centre in Amsterdam, said: “From a health-economic perspective cervical screening with a primary, stand-alone HPV test seems to be preferable based on this study.

“But a smear test is still a very useful way to estimate a woman’s risk of severe cervical changes and can help maximise the benefits of HPV testing in a cervical screening programme.”

Under the new screening process proposed by the researchers, women with a negative HPV test had an extremely low risk of CIN3, regardless of their smear test result, and so could safely return to routine screening every five years.**

Those who had a positive HPV test, and whose smear test results showed abnormal changes in the cervix, had a 42 per cent chance of having CIN3 and would be sent for a colposcopy to examine the cervix more closely.

But if smear test results in HPV positive women were normal, the researchers calculated that the woman had a five per cent risk of CIN3. This is too high a risk to safely return to normal screening, but not high enough to warrant an immediate colposcopy, and so the researchers recommended a follow-up smear in a year to monitor the cell changes.

If the result of this second test was also normal, the woman had a 1.6 per cent risk of CIN3 – which is low enough to return to routine screening.

If the second smear result was abnormal, the researchers said there was a 25 per cent risk of CIN3 and the woman would be referred for colposcopy.

Since 2008 in the UK, girls aged 12-13 have been vaccinated against two types of HPV which account for over 70 per cent of cervical cancers in the UK.
HPV testing can still be useful - even among women who have been vaccinated - to catch cervical cell changes caused by other HPV types. It can also protect women who haven’t been fully vaccinated.

More research will be needed to confirm the best strategy for cervical screening when most women have been vaccinated.

Sara Hiom, director of information at Cancer Research UK, said: “This study provides a very useful insight into how HPV testing could work if it were used as a major part of cervical screening.

“The findings help answer some of the questions that would need to be considered should the UK refine its highly effective cervical screening programme.

“The process outlined in this study would need to be fully tested to see if it is as effective as the study results suggest, and to establish some of the practicalities of using this combination of tests in the UK screening setting.

“The UK’s cervical screening programme already saves about 5,000 lives every year, but as with most tests, it is not perfect. So we welcome any new evidence which can help make cervical screening even more effective.”

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References

* Rijkaart, D., Berkhof, J., van Kemenade, F., Coupe, V., Rozendaal, L., Heideman, D., Verheijen, R., Bulk, S., Verweij, W., Snijders, P., & Meijer, C. (2012). HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications British Journal of Cancer DOI: 10.1038/bjc.2011.581

Notes to Editor

25, 871 women (aged 29 – 61) from the Utrecht province in The Netherlands, who were invited for the regular cervical screening programme between October 2003 and August 2005, were recruited for this study.

**For women with a negative HPV test, there was only a small, non-significant difference between the risk of CIN3 in women with a normal or abnormal smear result.

In the Netherlands, women are invited for cervical cancer screening every five years starting at 30 until they turn 60.

HPV infections are usually on the fingers, hands, mouth and genitals.

For most people, the infection will get better on its own and they will never know they had it. But in some people the infection will stay around for a long time and become persistent. Persistent infections are more likely to lead to cervical changes and cervical cancer.

Cervical screening is a method of preventing cancer by detecting and treating early abnormalities which, if left untreated, could lead to cancer in a woman's cervix (the neck of the womb).
The NHS Cervical Screening Programme routinely invites women aged 25 to 49 for a cervical screening test every three years, and those aged 50 – 64 every five years.

Since last year HPV triage has been rolled out in England as part of the cervical screening programme. Samples from women containing cells with low-grade abnormalities (borderline or mild dyskaryosis) are tested for high-risk HPV strains and, if positive, the women are referred to colposcopy.

These low grade cervical abnormalities only have a 15 per cent to 20 per cent chance of needing treatment and may clear up on their own but it does mean that women, whose samples are high-risk HPV-negative can be returned to routine recall as they are at negligible risk of developing cervical cancer in their current screening round and have a comparable risk to a woman with an otherwise normal cytology screening result. Consequently this means that women with low grade abnormalities can be more effectively triaged into subgroups that do and do not require colposcopy assessment.