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BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT
CASE NOTES
Programme No.5 - Cervical Cancer
RADIO 4
TUESDAY 12/06/07 2100-2130
PRESENTER:
MARK PORTER
REPORTER: LESLEY HILTON
CONTRIBUTORS:
ANNE SZAREWSKI
ALBERT SINGER
LOUISE CADMAN
RAJ NIIK
PRODUCER:
HELEN SELBY
NOT CHECKED AS BROADCAST
PORTER
Hello. Today's programme is all about cancer of cervix. Government advisors are meeting later this month to decide if a vaccine against cervical cancer should be included in our routine immunisation programme - as it already is in many other countries.
Cervarix and Gardasil are the world's first vaccines against any form of cancer. As such, their introduction is unlikely to be met with the same degree of scepticism that has greeted some other recent additions to the burgeoning list of routine jabs.
CLIP
I can understand parents fears of vaccines, we've all got fears of everything but if they saw how my daughter struggled to live, she so wanted to live for her children, they wouldn't think twice.
PORTER
But how does the vaccine work? How effective is it? And who is likely to be offered it, and when?
And if we have a vaccine that can prevent cancer of the cervix what are the implications for the NHS screening programme? Will women still need to come forward for regular smear tests?
CLIP
I'm in my mid-20s and I've never actually been for a smear test, I'm ashamed to say it. I do get the letters, I do think I really should go but I know I'm kind of embarrassed and I'm scared about what it's going to be and if it might hurt and yeah it's just - oh I don't know it just gives me the shivers thinking about it.
It isn't the most pleasant thing in the world, I have to be honest, but it is quite short and over fairly quickly. But I think the worst thing possibly is just the cold metal and the actual sight of it, the first time you actually go for one of these smears and you see one of those things right.
PORTER
My guest today is Dr Anne Szarewski from the Wolfson Institute of Preventative Medicine. Anne, what is it about the entrance to the neck of the womb - the cervix - that makes it so prone to cancer?
SZAREWSKI
Well it's actually a place where two types of cells meet and one type changes into the other. And when cells are in the process of changing or transforming they're actually vulnerable to attack then by things like a virus which of course we now know is the main cause of cervical cancer.
PORTER
This is the sort of soft, if you like, fluffy lining of the womb coming out into the hard world of the vagina - the different type of tissue?
SZAREWSKI
Yes.
PORTER
And you mentioned the virus there, we now know that cancer of the cervix is essentially a sexually transmitted infection, it's caused by this Human Papilloma virus. That's quite a recent discovery?
SZAREWSKI
We've now known about it I should think for about 15 years but at first I think it was treated with quite a lot of scepticism because people said viruses don't really cause cancer etc. etc. But in the last I'd say - in the last 10 years it's become unequivocal really that definitely it is the cause.
PORTER
Are there any reliable telltale signs to look out for, that might suggest the woman has cancer of the cervix?
SZAREWSKI
The big thing about cervical cancer is that you can pick up changes in the cells long before you ever actually get symptoms, so yes there are symptoms of sort of already cancer that's developed, you know like bleeding and so on, but you would hope that actually you could pick up abnormal cells long before the woman ever, ever has anything wrong with her, before she ever notices anything.
PORTER
And that's the basic explanation behind the smear test. Can you just explain: It's doing what?
SZAREWSKI
The idea of the smear is that you basically scrape off some cells from that transformation zone in the cervix and you can tell then if some of them are changing abnormally and that gives you a sort of 10 year period really in many cases where you can actually treat that woman if she needs it investigated and so on because from nothing, from normal, to actual cancer tends to take about 10 years.
PORTER
Well we'll come back to smears a little later. First another preventative measure - the vaccine we were mentioning.
Cervical cancer, as we have heard, is caused by infection with the Human Papilloma virus - HPV. A virus carried, in one form or another, by as many as 12% of sexually active women in the UK at any one time.
So, in theory, if you develop a vaccine to stop the virus getting a foothold, you should be able to prevent the cancer. And that is exactly how it is has turned out. Professor Albert Singer is Consultant Gynaecologist at the Whittington Hospital in North London.
SINGER
The virus is very common - 80% of sexually active women at some time in their life will come across this virus. The good news is even though it's as common its serious consequences are extremely rare. It's an infection - there are over a hundred types of the HPV virus, there are about 15 or 16 that are associated with the cancer of the cervix and what we call the lower genital tract - the vagina, the vulva and the anus.
PORTER
So of those 10-12% of women who might have it at any one time how many of them are likely to know that they've got it through some form of outward symptom?
SINGER
Probably about 1% of the population at one time will have outward signs in the form of actual genital warts. And the rest of them it will be silent. Now the types that cause genital warts are what we call Type 6 and 11 and they are different to the ones that I've mentioned that cause the cancer. Men also have it, it's sexually transmitted, they get it on their genitals and a lot of the time unless they have an actual wart it's not recognisable.
PORTER
When the HPV cancer of the cervix story first came out my understanding was certainly that HPV accounted for the lion's share of cases of cancer of the cervix but not all, is that still our understanding?
SINGER
Our understanding is that as we find more types associated virtually every single cancer of the cervix has some form of HPV present associated with it.
PORTER
And what do we know about the small minority of women who have the HPV virus and go on to have problems with their cervix, are there some characteristics that will make it more likely for the HPV to be cancer causing, rather than just an infection that they eventually get rid of ...?
SINGER
Well what happens when you're young, under say the age of 30, you may get up to 25% of young women carrying it. But they will get rid of it - 90-95% of young women will get rid of it in the space of about 12, 16, 18 months. There are a very small number, maybe there's 5%, who persist with the infection. Now either they're getting reinfected again with multiple partners or a genetic reason why they can't clear it. Now as I said it is a very common infection, it is a very rare disease. We find in this country, if we're screening for cervix cancer, and the way we do it is with a smear test, we find up to 7% of women who go to have a smear test will have an abnormality but a very small number of those will have the types that will go on if left to cancer because cancer of the cervix is a preventable disease if you find it in its pre-cancerous stages and that's why we do these smear tests.
PORTER
When did the idea of producing a vaccine first come to light?
SINGER
It developed in the early 1990s, Professor Ian Fraser, originally from Glasgow, now working in Brisbane, tried to develop an inert case. So what he's come up with is a concept of what's called the virus like particle, it is a particle that looks to the body as though it is a virus and the body then produces a massive amount of antibody, it fools the body into believing that there is a virus present, there is no live virus, it's virtually a dead shell. So the safety of this is paramount and that's what it's dependent on.
PORTER
You've mentioned that there are many, many different types of HPV, what types do the vaccines contain and how were they selected?
SINGER
As I mentioned before the benign lesions - say the warts - are associated with type 6 and 11, the malignant and pre-malignant stages are associated with type 16, 18 and there are a few other ones as well, probably about another 10. But 70% of all cancers and pre-cancers have type 16 and 18. There are two vaccines presently being manufactured, one is already released in this country, the other one will be here soon. One of them is what we call a quadrivalent, which has type 6 and 11, so it's excellent against warts and type 16 and 18 which will fulfil the role of pre-cancer and cancer. The other vaccine has just type 16 and 18 present.
PORTER
And how effective have these vaccines been shown to be in the early trials?
SINGER
Extremely - extremely effective. If you vaccinate young women say at 11 and 12 and you can up to at any age vaccinate but the best age is 11-12 and if they have not been exposed to type 16 and 18 then there is virtually 100% protection.
PORTER
And how long is it likely to last?
SINGER
There are studies that show that certainly at five years it's still highly effective. The experts in this field on their modelling experiments believe it's probably 15-20 years. The answer is we don't know as yet, I suspect that there may be a booster needed maybe at 10 years but again that's speculation. But certainly from some evidence at 5 years the immune response is still going strong.
PORTER
Professor Albert Singer talking to me earlier.
You are listening to Case Notes. I'm Dr Mark Porter and I am discussing cancer of the cervix with my guest Dr Anne Szarewski.
Anne, first of all why do we need the vaccine, how common is cervical cancer in the UK?
SZAREWSKI
Well in fact we're now very fortunate in that only - one should never say this - but only about 3,000 women a year get cervical cancer in the UK. And that's because we've got such a good screening programme now. But of course we do have hundreds of thousands of women who have abnormal smears and although most of them will not go on to get cancer they do suffer all the anxiety and everything actually that the women who get cancer suffer from as well.
PORTER
Listening to the professor there talking about the vaccine it raises a number of issues. Firstly, do you think it's likely to become part of our routine programme - we've said already that the advisors are at a meeting, almost as we speak?
SZAREWSKI
I think it's very likely that there'll be a vaccination programme for 12 year old girls. The interesting question will be whether in fact they do what's called a catch up programme for older women, say up to 16 or 20.
PORTER
There's been some criticism about giving it to 12, 13 year old girls from some angles saying that you know it encourages promiscuity, what's your view on that?
SZAREWSKI
Well there are two aspects of this: One is that in actual fact if you look at the immune response that's generated by the vaccines it's actually best in the younger girls, so it's actually best given to the teenage girls. But secondly, this whole business of it'll encourage promiscuity, you know did car accidents increase when safety belt wearing was mandatory, you know I don't think that's true. And I think also because the vaccines don't protect against things like chlamydia and gonorrhoea and so on, so why should anyone think that they can be promiscuous just because they've had this vaccine?
PORTER
What about older women, what's your position on women who are sexually active and out there and who are going to miss out on this routine jab?
SZAREWSKI
Yes, I think that in an absolutely ideal world where money was no object I think it would be wonderful if everyone could be vaccinated. I think obviously in a very expensive vaccination programme we're going to have to make decisions. And so certainly I think that it's unlikely that anyone over the age of 20 will be given a free vaccine. But I think that they would still benefit from it if they're willing to pay for it. They probably won't get, perhaps, as much benefit as someone who definitely has never been exposed to the HPV types in the vaccines but the studies show that only around 20% of women actually have been exposed, the older women have been exposed to the - to type HPV 16 and 18. So in actual fact the majority of women would get at least some benefit.
PORTER
And you aim - would this be aimed at women who are shall we say single and out on the dating scene again rather than someone who's in a stable relationship - married, for instance, and has been with the same partner for 10 years, because if they've not met the virus they're unlikely to meet it again aren't they?
SZAREWSKI
Well I think that's a mistake many people make you know because we now have a divorce rate that's getting towards one in two, so you may think you're very happily married at the moment but what's going to be the case in 10 years time? And so I think it's a foolish person actually who thinks they're going to be definitely happily married forever and of course who thinks that their husband will never have an affair.
PORTER
I don't want you to pick one vaccine over another but we've already said that one contains - offers protection against cancer, the other offers protection against cancer and warts. I mean why would a woman not want to go for the one that offers protection against both?
SZAREWSKI
Yeah I think on the face of it that seems obvious. I think there are however cultures in which it will be acceptable to vaccinate perhaps against cervical cancer but they wouldn't find it acceptable to be offering vaccination against sexually transmitted disease, even though I've said I don't think that's a good argument but I think there are cultures where that'll happen. And also I think there is also a potential advantage which still has to be proven to the vaccine that only contains type 16 and 18, which is that because of slight differences between the vaccines they're hoping their vaccine will give stronger, a longer lasting immunity and perhaps slightly better cross protection against other HPV types that actually aren't included in the vaccine.
PORTER
So these are the types that cause that other 30% of number of cases of cancer?
SZAREWSKI
Yeah.
PORTER
And briefly, cervical cancer's not the only cancer caused by HPV?
SZAREWSKI
No that's right, in fact HPV 16 and 18, the two types in the vaccines, they also cause cancers of the vulva, the vagina, they cause anal cancer, they actually cause about 20% it appears of head and neck cancer, some bladder cancer. There was a paper just in the last week suggesting that some breast cancers even may be associated with these HPV types. So actually there's potential benefits, of course and none of them proven at the moment, except vulva and vagina actually have already been shown, but you know potential benefits all over the place.
PORTER
Well, pending approval from the Joint Committee on Vaccination and Immunisation, our best defence against cervical cancer remains the NHS screening programme based on the smear test.
The programme is the most effective of its type in the world and is estimated to save up to 5000 lives a year. Smears are offered routinely to all women between the ages of 25 and 64 - three yearly up until the age of 50 and five yearly thereafter. And recent advances have made testing more accurate than ever.
Louise Cadman is a research nurse consultant for Cancer Research UK.
CADMAN
There are two types of speculum that we currently use, although they're both pretty much the same. You may be in a practice where they use a disposable speculum, we don't use disposable speculum here, we use the ones that everyone may be familiar with, which is the old ratchety metal ones. So you hear a lot of clanking and crackling.
PORTER
And this is the instrument that basically opens the walls of the vagina so that you can see the cervix.
CADMAN
Yes. And sometimes people refer to it as having a bit of a duckbill. What we do is we tend to open it to the width of the cervix, which is about one and half to two centimetres at the end.
PORTER
It's a cold metal instrument, is it uncomfortable?
CADMAN
Some people will say it's uncomfortable, I think you're perfectly within your rights to ask your doctor or nurse to warm it up before they use it because that makes a big difference because it can be a shock to the system. It's uncomfortable primarily because very often people's reflex is to push against it - they feel tense, they feel nervous and therefore their vaginal muscles press in the opposite direction from the person just trying to open the speculum a couple of centimetres. And that's what causes the discomfort.
PORTER
Okay so the speculum's in, we can see the cervix, we've got a good view of the cervix, which of course doesn't always happen, it can be a bit tricky in some women but let's assume we've got a good view of it. Now what happens?
CADMAN
What happens now is we actually need to take the sample from the cervix, so we need some kind of sampling device. In the past what we would have used is this, which is a spatula, it's got a slightly pointed tip which we insert into the hole and we literally rotate the spatula around the hole in the middle whilst making contact with the cervix.
PORTER
And then you did what with the sample?
CADMAN
We then - unfortunately sometimes you may feel that you've been left while the smear taker is much more attentive to what they're doing with their sample, the reason for that is we then would have had to fix it on to a slide immediately, if we don't fix it on to a slide immediately the cells dry out, they become slightly desiccated and the lab can't read them properly.
PORTER
And this is where the word smear comes from, you literally smear it on to a glass slide and then put some fixing solution over the top.
CADMAN
Yes, yeah.
PORTER
But that has changed and we now have the newer [indistinct word], talk us through this.
CADMAN
What we're using now is a technology called liquid based cytology. The main difference is we now don't fix it on to a slide but we put it into a liquid preservative. Now you may find that different places use different sampling devices. What's most commonly used now is a plastic brush, it's about a centimetre and a half wide and that literally will ...
PORTER
And v shaped at the end.
CADMAN
V shaped, yes, yes, almost like a chevron, I guess, is the closest you can get. There are several real selling points from liquid based cytology. The main selling point is the unsatisfactory smear rate, so that's a smear that doesn't give a result, it's not an abnormal result but it just means that the lab can't read it, maybe because there are blood cells blocking the view, it may be there are mucus cells or bacteria or simply that there aren't enough cells on the slide or that the slide is a bit thick and they can't read it.
PORTER
So for whatever reason it's a poor quality sample.
CADMAN
Exactly. The difference with the liquid based cytology is instead of giving 1 in 10 smears as an unsatisfactory smear it should be only producing 1 in 100 smears as unsatisfactory.
PORTER
Because of course the women who have unsatisfactory smears have to come back and have another one.
CADMAN
Yes exactly. So the slide is better. So in theory if the slides are clearer and uniform and easier to read it may well be that we can get our smear reporting turn around time to come back much more quickly so that you receive your result more quickly. And there's also another benefit in that not necessarily all the liquid will be used for the smear so you may have the liquid available for chlamydia testing, gonorrhoea testing, HPV testing also from the same sample, so it may well be that more than one test can be done from that one uncomfortable or upsetting or embarrassing examination and that would be certainly a positive thing.
PORTER
Louise Cadman talking to me during a busy clinic at the Margaret Pyke Centre.
Anne, what happens if a woman's not sexually active, she's a virgin?
SZAREWSKI
If a woman is actually a virgin she doesn't need to have smears. But I think some women think that if they haven't had sex for a long time or some people think lesbians don't need to have smears because they're not having sex with men but in fact many lesbians have had sex with a man at some point and then for the rest of their lives they will be at risk of cervical cancer. And again even if - the last time you had sex was years ago you're still at risk.
PORTER
But to be clear if you're not sexually active and you're a virgin then you won't - the idea is that you will not have encountered the HPV virus and therefore you're not at risk, you do not need a smear.
One of the criticisms of the screening programme historically is that it is not very specific - that an awful lot of women are worried unnecessarily when in fact they haven't got anything serious wrong?
SZAREWSKI
I think that is true and it is a legitimate criticism and I think again it's one area where the vaccines could make such a difference because of course not only will they reduce cervical cancer rates but they'll also reduce the number of abnormal smears, so women are less likely then to have an abnormal smear.
PORTER
And how many abnormal smears might there be in a typical year - I think we do something like 3.5 million smears a year or 4 million smears a year?
SZAREWSKI
It's about 10%, so it's about 300,000 women each year are getting a result saying you have an abnormal smear.
PORTER
Talk me through - I mean there's obviously no such thing as an average woman - but talk me through a typical case that might warrant further investigation. A woman has an initial report for an abnormal smear and needs to go back say at six months for a repeat one, that doesn't look quite right as well, then what's the next stage?
SZAREWSKI
Well at the point, by which time she's usually phenomenally anxious, she usually will get referred for colposcopy, which is basically a sort of further examination, a closer look at your cervix through a magnifying glass if you like.
PORTER
Because the smear test is a fairly crude test - looking at cells that have been scraped off - it's the colposcopy that tells us more.
SZAREWSKI
Exactly.
PORTER
Well we sent Lesley Hilton to a busy colposcopy clinic at Queen Elizabeth Hospital in Gateshead to find out what's involved.
ACTUALITY Nurse with patient
Right if I can just lay you back, alright, alright? And I'll just put this sheet over you. And if I can just pop your feet up on to these stirrups.
HILTON
Having an abnormal smear test does not necessarily mean a diagnosis of cervical cancer. But obviously for the women concerned that is their big fear and most of them are very anxious about having to go for further tests. In Gateshead Raj Niik, consultant gynaecological oncologist, is performing a colposcopy.
ACTUALITY
Okay this bit doesn't take more than a few minutes and it's simply going to feel like when you're having a normal smear taken okay?
HILTON
Colposcopy is a procedure which allows a more detailed look at the cervix. A high powered light source is combined with a magnifying glass. A solution of weak acetic acid is often used to allow the cells to undergo visual changes, which make it easier for the doctor to see what's going on.
ACTUALITY
What I'm going to do is just take one or two very small biopsies from those areas. Okay, just cough.
HILTON
A punch biopsy gives more information. This involves taking a sample of tissues from the cervix which is then sent for analysis. The results can show either nothing to be concerned about or a label of CIN1 where one third of the thickness of the lining of the cervix shows abnormal cells, CIN2 where two thirds are abnormal, or CIN3 where the cervix is completely covered with abnormal cells. But not all women will need immediate treatment, as Raj Niik explains.
NIIK
Some of the very early changes don't require any treatment at all. CIN1 for instance, many practitioners would not treat early changes because we know that the great majority will revert back to normal simply through conservative measures. For high grade pre-cancer, because of the concerns that the great majority will go on to develop cancer at some point in the future and for many women that can be many, many years, there are various ways of treating the lesions but the commonest method that's used in the UK is what's LETTZ procedures or loop treatment.
HILTON
Basically all the treatments on offer do the same thing which is remove or destroy the abnormal cells. Laser ablation, cold coagulation and cryotherapy treat just the abnormal cells - allowing the normal ones to grow back again. LETTZ, or large loop excision of the transformation zone, removes the whole area of abnormal cells completely. The area is cut away using a loop of wire and an electric current and is done under local anaesthetic.
HILTON
Kim has had two abnormal smears in a row and has come to the clinic today for a colposcopy. It wasn't an experience she enjoyed.
KIM
I was told it was going to be like a smear and it was a bit more invasive I found. The nurse and the doctor was absolutely brilliant, I couldn't fault them, they were brilliant, they put me at ease, talked me through it, held my hand even because I was so nervous. Told me everything they were doing but it was uncomfortable at times and you could feel everything that was going on and I was glad when it was over to be honest.
HILTON
At the Queen Elizabeth Hospital they run their colposcopy clinic as a one-stop-shop, this was designed to minimise the anxiety felt by the women attending which has been shown by research to be as severe as if facing a major operation.
Tito Lopez is the consultant gynaecological oncologist at the hospital.
LOPEZ
We've improved the situation for women who are referred with mild abnormalities, that's borderline or mild discarrioses by running what we call a one stop clinic. Those women are seen in the morning, colposcopy is performed, punch biopsies are taken from many of those areas and those biopsies are processed over about a two hour period and those women return at lunchtime and we will have the result and will be able to tell the women that their histology was mild and we don't need to do any treatment or we should do treatment. And we'll offer treatment at the same time. With women referred with high grade smears, that's moderate to severe discarrioses, we tend to offer, what we call, a see and treat, or a select and treat, policy. We will do a colposcopy and if the features are in keeping with CIN2 or CIN3 we will offer treatment at the same visit by a loop biopsy.
HILTON
Kim has had her results back and all is well. She doesn't need further investigation or treatment.
KAREN
The fact of getting it all done on one day that's brilliant, it is great 'cos you couldn't go away and then just wait for results in the post 'cos it would drive you round the bend! [Laughter]
PORTER
Anne, the NHS cervical cancer programme may have saved thousands of lives, but, given that future generations of women are hopefully going to be vaccinated against HPV, has it had its day?
SZAREWSKI
Not yet because of course for the whole generation of women who are already sexually active they won't get necessarily as much benefit from the vaccine, even if they have it as the girls who are still virgins. So that whole generation will still need to have smears, so we're going to need them for at least another 20, 30 years.
PORTER
And what about that generation - say we start vaccinating next year, 13 year olds, 12-13 year olds in this country, we're not going to protect them against every single case though because we're only giving them protection against the strains that cause 7 out of 10 cases?
SZAREWSKI
That's absolutely true and of course I think it is a dream, you know I think it's such a lovely idea that the girls who are vaccinated who are sort of 11, 12 years old maybe they won't ever need to have smears.
PORTER
But they won't be fully protected but it'll be such an unusual thing that they probably won't benefit from screening.
SZAREWSKI
That's the problem but I think by the time you've actually got rid of 70 or maybe 75% of cancers it'll actually be such a rare disease it won't really warrant a screening programme anymore and I think that's where it's going to start to be problematic. But I hope that by then we'll actually have newer vaccines which will have more virus types in them and so in actual fact the level of protection will get higher and higher.
PORTER
Briefly and we must end on men, we haven't mentioned them at all in the programme, do you think there's any benefit in vaccinating them?
SZAREWSKI
I think two reasons why we should be vaccinating men. One is that not all women will get vaccinated, so we need to vaccinate men to kind of protect everybody. And we mustn't forget about gay men who are actually at greater risk of HPV 16 and 18 related anal cancers and also warts and I think they don't - we shouldn't ignore them, they should be included as well.
PORTER
Dr Anne Szarewski, thank you very much.
Next week's programme is on lung cancer - 9 out of 10 cases are smoking related. And I'll be pre-empting the nationwide ban on smoking in public places with a look at the latest methods for helping smokers quit. And I'll be finding out if CT scans are a useful way to screen for lung cancers and catch them at a stage when they might still be treatable. If so who should consider having one and when.
ENDS
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