NCRI conference: How could the HPV vaccine change cervical screening?

The cervical cancer screening programme has been around since 1988. In that time, it has saved as many as one hundred thousand lives from cervical cancer. Now, in 2010, the programme is as effective as ever and it’s still vital that women take up the invitation to go for screening when they receive it.

But some things have moved on. We know more about cervical cancer and the virus that causes it: human papillomavirus, or HPV. Testing for HPV itself, could be an attractive alternative to the current “smear test”, which looks for abnormal cells in the cervix.

We also have a vaccine against two of the most common strains of HPV – 16 and 18 – the ones that are most likely to cause cervical cancer. The vaccine, known as Cervarix, has passed a number of rigorous clinical trials and it’s both safe and effective. It doesn’t cover every strain of HPV, but it has the potential to prevent at least seven out of ten cervical cancers and probably more.

In the UK, the vaccine is now being offered to girls aged 12 to 13, who are given three injections over six months. There has also been a two-year catch-up programme to vaccinate girls aged between 13 and 18. The early results are very encouraging – around 80 per cent of girls aged 12 to 13 have been vaccinated with all three jabs.

According to Professor Peter Sasieni, one of our scientists at Queen Mary, University of London, these two advances – HPV testing and the vaccine – have big implications for the UK’s cervical screening programme.

Speaking at the NCRI Cancer Conference in Liverpool, Sasieni said that HPV testing should, in his opinion, replace the current smear test as the main method of cervical screening. This would mean that screening could be offered less frequently while still saving as many lives, or even more. And women should be invited for screening at different ages depending on whether (and when) they received the HPV vaccine.

Why HPV testing?

Compared to the standard smear test, an HPV test is better at finding ‘pre-cancerous’ changes in the cervix that could eventually develop into full-blown cancer. For every 100 women with such changes, the smear test will identify anywhere from 50 to 80 (depending on the country), but the HPV test will find more than 96. In technical terms, it’s a more “sensitive” test.

But this comes at a cost: the HPV test is also more likely to come up with false alarms, indicating pre-cancers when there aren’t any. For every 100 women without abnormal cells in their cervix, the smear test will incorrectly identify four of them as having pre-cancers, but the HPV will identify nine. Technically, it’s a less “specific” test, and this means that more women might face extra anxiety and further rounds of testing.

There is also a risk that among younger women, HPV testing would pick up some pre-cancers that would regress on their own and never go on to cause women any problems. This is known as overdiagnosis.

So if the UK switched from the smear test to an HPV test, we would detect cancers (and the changes that lead to cancer) earlier on, at the cost of more false alarms. Sasieni thinks that the way around this is to test women for HPV less frequently than they currently are.

At the moment, women are invited for screening every three to five years, depending on their age. If the UK switched to HPV testing, even if that gap was lengthened, you would still pick up or prevent the same number of cancers because the test is more sensitive. And even though you might get more false alarms in each round of screening, you’d have fewer in the long run because there would be fewer rounds.

An HPV test also tells you a lot about a woman’s future chance of developing changes that could lead to cervical cancer. Women who test positive for HPV16 – the most dangerous strain – have an almost one in four chance of developing such changes within 10 years. Those odds fall to one in eight for women who test positive for other common cancer-causing strains of HPV (such as 18, 35 or 41) and just one in 40 for women who test negative for HPV altogether.

This means that if women test negative for HPV, we can confidently predict that they won’t need any follow-up tests. If they test positive for HPV, and strain 16 in particular, they should be referred for a colposcopy, another examination of the cervix.

What about the vaccine?

The HPV vaccine changes things even further. Women who are vaccinated before they start having sex should be fully protected against the two major strains of HPV –16 and 18 – and the cancers that they cause. However, they could still be infected with other rarer strains of HPV that can also cause cancer, which is why it is still important to screen women who have been vaccinated.

However, Sasieni thinks that the programme can afford to screen vaccinated women less frequently using HPV testing, maybe even just twice in their entire lives. This is because it generally takes a minimum of eight years for a cancer to develop after infection with HPV, and even longer after infection with the strains that the vaccine doesn’t cover.

He proposed that:

• women who are vaccinated between ages 11 and 14 could be screened just twice at the ages of 30 and 45.

• women who are vaccinated between ages 15 and 23 could be screened once at the age of 25, and then twice more at 35 and 50. The vaccine isn’t as effective in women who have already been infected with HPV, which can happen soon after they start having sex. So the first screen at 25 is meant to find out which women have been protected by the vaccine and which ones haven’t.

• women who haven’t been vaccinated (or who haven’t completed all three doses) should be screened more regularly at the ages of 25, 30, 35, 45 and 55. As mentioned earlier, the use of HPV testing allows screening to happen less regularly.

Moving ahead

Sasieni’s proposals would represent a big change to the cervical screening programme, which is already working well and saving thousands of lives. It is not a change that should be entered into lightly.

He suggests that if the changes are put into place, they should be rolled out gradually, so that we can learn as we go about what works and what doesn’t. He estimates that it would take five years to convert the current programme into this suggested version.

It’s particularly important to tread carefully, because, as a rule, it’s very hard to undo changes to screening programmes. These changes would probably be irreversible. This is because interpreting the results of smear tests is very difficult, and relies on the experience of ‘cytologists’, doctors who are familiar with cells under the microscope.

The UK has some of the best cytologists, who are excellent at working out which cells show potential signs of cervical cancer and which don’t. This is why UK trials have found much better results for the smear test than those in many other countries. If we move from smear tests to HPV testing, we would lose that experience and it would be almost impossible to recover it.

So before implementing any big changes to the screening programme, it’s important to be sure about the impact of those changes. The scenarios that Sasieni has suggested are based on sound logic. Now, they will need to be tested in mathematical models to see how many more lives will be saved, how many false alarms will result, and how much this will all cost to a cash-strapped NHS.

This is all good news. It just shows how far we have come in beating cervical cancer and while there is still a long road to travel, the combination of screening and vaccination should eventually make this a very rare disease indeed.

In the meantime, the message is still a very simple one: take up the invitations for cervical screening and HPV vaccination, as appropriate. They could save your life.

Ed