Expert opinion: “Now we need to plan for first-line HPV testing”

• Cancer Research UK-funded screening expert, Professor Peter Sasieni, gives us his thoughts on an important development in cervical cancer research

“Plans should be made for the roll out of HPV testing nationally”

New research from the US, published last night in the Journal of Clinical Oncology, has significant implications for the NHS cervical screening programme.

The headline finding, as Cancer Research UK reports on its newsfeed  is that testing a woman’s smear samples for the human papillomavirus (HPV) predicts who is likely to go on develop early signs of cervical cancer up to 18 years later.

And the study, which involved 4,000 women, showed the power of testing samples for the virus was much greater than the existing test – cytology – which looks down a microscope for abnormal cells.

This is not surprising. But it is new, and extremely important, as we’ll see below.

HPV and cervical cancer

We’ve known for some time that women without an HPV infection will not get cervical cancer – this research won Harald zur Hausen the Nobel Prize in 2008. We’ve also known that HPV infections are extremely common, and that the vast majority disappear naturally without any ill effects.

On top of this, HPV infections tend to occur in teenagers and young adults, but cervical cancer develops mainly in middle and old age. So this tells us that it takes between 10 to 60 years for an HPV infection to result in cervical cancer.

Cervical cancer prevention in the UK

Currently, women in the UK are offered a cervical screening test every 3-5 years from their mid-20s until their mid-60s, and their samples are sent off for cytology testing. This has dramatically reduced the number of cases of, and deaths from, cervical cancer.

In women who have borderline or ‘mildy abnormal’ smear test results, samples can be re-tested for HPV and this is now happening in much of England. But the evidence has been building for some time that the HPV test could be at least as good as cytology as a first-line test.

It’s worth stressing that, from a woman’s point of view, there’s no difference in what they experience – the its just the way the subsequent tests in the laboratory are carried out that differs

As well as screening, girls in year 8 (aged of 12 and 13) are now offered a vaccine that protects them against the two most potent cancer-causing strains of HPV. Since the programme began in 2008, more than 8 out of ten of girls in this age group have received all three doses of the vaccine.  This level of uptake is better than anywhere else in the world.

What does the new research mean?

Until now, we had only known that the presence or absence of HPV could predict whether women might develop cervical cancer (or the early signs of the disease – cervical intraepithelial neoplasia, or CIN) over the next ten years.

But these new observations show, as many had assumed, that women without an HPV infection are at low risk of cervical cancer or CIN even 10 to 18 years after testing. (The same is not true for cytology: women with a negative cytology test are no less likely to develop CIN or cancer 10-18 years later than are women with a positive cytology test). This has two important public health consequences.

Firstly, and excitingly, they point to the very long-term benefit of HPV vaccination. By preventing HPV infection in young women, vaccination is likely to prevent cancers at least until the age of 40 and could even give life-long protection. Much of this protection will occur even if the potency of the vaccines against new infections wanes.

(We have no evidence that the protection against infection does wane, but since many vaccines become less effective after 10 years, it is good to know that vaccination will still protect against cancer, even if they stop protecting against infection).

Secondly, using HPV testing, the time between cervical screenings could safely be increased to 6 or even 10 years in those who test negative for HPV aged 30. This would have huge consequences for women and also – in economic terms – for the health service.  Women would be offered perhaps five screens (instead of the current eleven) between the ages of 30 and 64.

What are the issues with HPV testing?

Unfortunately, we still don’t know how best to look after women who test positive for HPV, but who don’t have early signs of disease. Cytology is good at identifying those who may benefit from treatment straight away, but what about women who have an HPV infection and normal cytology? These women are not at immediate risk of cervical cancer, but remain at increased risk of developing cervical disease as long as their HPV infection persists.

Studies have shown that more than 1 in 4 women aged 25-29 coming for cervical screening in the UK test positive for HPV. It would be a real challenge not to cause more harm (in terms of anxiety and over-treatment) than good by HPV testing in such young women.

So we need to determine the optimum age to begin testing for HPV, and how to screen younger women.

What should happen next?

The evidence that we should begin planning for a switch to HPV-only testing from aged 30 is now becoming overwhelming. Some think we need to ‘dual test’ – i.e. run both cytology and HPV testing in parallel on all samples. I disagree. As this study shows, the risk of developing significant disease in the next 10 years in women who have an abnormal cytology result in the absence of HPV infection is so low as to be negligible.

The NHS has announced plans to pilot its introduction in a few small centres in England. These are to be welcomed, but plans should be made for the roll out of HPV testing nationally within the next five to six years, so that all women can benefit from these advances.

Peter Sasieni is Professor of Biostatistics & Cancer Epidemiology at the Wolfson Institute of Preventative Medicine in London. He is funded by Cancer Research UK.

Reference

Castle, P.E., Glass, A.G., Rush, B.B., Scott, D.R., Wentzensen, N., Gage, J.C., Buckland, J., Rydzak, G., Lorincz, A.T. & Wacholder, S. Clinical Human Papillomavirus Detection Forecasts Cervical Cancer Risk in Women Over 18 Years of Follow-Up, Journal of Clinical Oncology, DOI: 10.1200/JCO.2011.38.8389