The more Pap tests, the worse

The reason why this website is called Cancer Screening reflects the issue that intrigues me the most in the cervical cancer debate. As I said before, in many countries, including Portugal where I come from, screening for cervical cancer usually starts as early as women become sexually active. In England it doesn’t start until the age of 25.

Different factors should be considered when judging the quality of a screening programme, regardless the type of cancer it applies to. Budget, culture and private health services are just some of them, which partly explains why there isn’t a common cancer screening programme, for example, on a European level.

Portuguese GP
Dr Armando Brito de Sá

I spoke to one expert who is particularly concerned about such discrepancies. Dr. Armando Brito de Sá is Professor of General Practice and Family Medicine at the Medical School of Lisbon University.

He agrees with the screening programme adopted by the NHS. Both the age to start screening and the frequency (every three to five years) are recommended for the Portuguese primary care services, following the British model.

Some important bodies, such as the U.S Preventive Studies Task Force (USPSTF), still recommend screening once a woman becomes sexually active. But the Portuguese expert highlights the position taken two years ago by the American College of Obstetricians and Gynecologists (ACOG):

Screening before age 21 should be avoided because women less than 21 years old are at very low risk of cancer. Screening these women may lead to unnecessary and harmful evaluation and treatment.

According to Dr. Brito de Sá, “this is a surprising statement given that it comes from an organisation of specialists [and not of a wider range of health professionals], which is very good news”. In his opinion, such organisations tend to be more aggressive.

ACOG also states cytology should be made every two years – a frequency that “prevents cervical cancer just as well, has decreased costs, and avoids unnecessary interventions that could be harmful.”

There is no scientific evidence that supports doing a Papanicolaou test every year, the GP adds.

The more medical exams, the healthier: a wrong message

One of my questions was that although the Portuguese health service takes the NHS as an example, both systems can never be totally similar since the private sector plays an important role in the country.

According to Portuguese database Pordata, 1,485 gynaecologists/obstetricians and 5,160 GPs were active in the country in 2009.

"Pap" test

Dr. Armando Brito de Sá points out that, although most people are consumers of the national health service (SNS in Portuguese), there is an overuse of medical exams in the private sector – not only in Portugal but worldwide. “This happens because of this general and wrong idea that the more exams we do, the better health we have.”

In line with this, I know many people who ask their private gynaecologist to be screened every year – sometimes even twice a year. So I asked Dr. Brito de Sá whether patients understand that paying for an exam could be more harmful than attending a national programme that recommends less frequent smear tests.

“Patients are not idiots,” he answers. “When you tell them the facts, they understand and are capable of making their own decision”.

Overscreening is a direct breach of “Primum non nocere”, an ethic principle taught in medical schools which means “First, do no harm”

And the facts are clear in his words: “The problem caused by early, frequent screening is not only the very small number of lives it would save but mainly the thousands of young women that are unnecessarily overwhelmed with additional exams whenever they have an abnormal test.”


Making medical students aware of different evidence-based policies

While lecturing the future generation of doctors, one role of Dr. Armando Brito e Sá is to make them understand that governments do not always follow the latest, best scientific advice.

He points out the dangers of overprevention and overmedication – an idea that was highlighted in 2001 when the American Family Physician journal published these Screening Guidelines.

Numerous medical organizations have developed cancer screening guidelines. Faced with the broad, and sometimes conflicting, range of recommendations for cancer screening, family physicians must determine the most reasonable and up-to-date method of screening.

Finally, the Portuguese expert shows conviction in saying that government’s policies are just partly determined by scientific evidence. The implementation of the HPV vaccines in different national programmes was “inevitably political, because of the excessively heavy disease-awareness produced in the media by the vaccine manufacturers.”


UK: Cervarix is cost-effective

Yesterday, The Guardian Science Blog has helped me launch the debate on HPV vaccination. There you can read a blog post on my first findinds and thoughts.

In the past weeks I’ve come across very interesting studies about the two vaccines that can prevent cervical cancer.

First of all, in this Cancer Research UK’s page you can read very clear information about the human papillomavirus.

Secondly, it is worth reminding the main differences between the two vaccines.

1 – Cervarix:

2 – Gardasil:


Just a few days ago, the Department of Health has responded to my Freedom of Information (FOI) request. My main questions were related to the scientific evidence that led the UK Government to choose Cervarix over Gardasil. They clearly admitted that the Joint Committee on Vaccination and Immunisation (JCVI) recommended the use of Gardasil as it protects against not only cervical cancer but also genital warts, so the decision was ultimately determined by matters of cost-effectiveness. We all would like to know how much the UK has paid for the vaccine, neverhteless the FOI response stated that:

The information in question has been identified at all stages as being commercially sensitive and we have considered your request very carefully, taking account of all the circumstances.  In short, as explained below, we have reached the conclusion that the information you have requested should be withheld as exempt under FOIA section 43(2) which is available to protect commercial interests.

Now with the help of Dr Peter English, who is editor of Vaccines in Practice magazine and has been a consultant on vaccine boards for various vaccine manufacturers, I found out that the scientific evidence is not yet enough to permit any manufacturer to make claims of duration of efficacy beyond that which has been proved. One should not forget that such HPV vaccination programmes have been implemented a few years ago only, so we need to wait and remain monitoring the effectiveness of the programmes in order to draw conclusions.

One other thing I found out is that scientific evidence released after the UK Government went for Cervarix is that this GSK vaccine may offer cross-protection to other cancer-causing HPV strains that Gardasil doesn’t. Check out this study:

Human Papillomavirus (HPV) Vaccines: Limited Cross-Protection against Additional HPV Types, published in The Journal of Infectious Diseases

Gardasil and Cervarix
As you can see from this table, Cervarix offers cross-protection to HPV 45, which according to this study should be given priority in cancer prevention.

In addition, there are other worth mentioning aspects raised by Dr Peter English. Please note that these are his own opinions and not those of his employer.

Cervarix and immunity

Cervarix, which only contains the two oncogenic types, also contains an “adjuvant” – a chemical which makes the vaccine stimulate a higher level of immunity. GSK, who make Cervarix, claim that this means that the vaccine generates a stronger immune response, with more antibodies produced (a higher concentration of antibodies to the vacine in the blood stream – “higher serum levels”). As serum levels fall gradually over time, they suggest that this means that people given Cervarix will have immunity that will last for longer.

Gardasil, by contrast, while it protects against genital warts, is unadjuvanted. The antibody levels it generates are not as high as following Cervarix. Sanofi Pasteur Merieux, who make (or market) Gardasil in Europe claim that the levels are sufficient to give good immunity that is likely to last as long as it’s needed.

Are three doses necessary?

If antibody levels continue to fall as the graphs – and experience with other vaccines etc. – suggest, both vaccines are likely to provide protection for 10-25 years – but it’s hard to know for how much longer than Gardasil Cervarix will actually protect women. A single booster dose years after the original course could be expected to push antibody levels back up to the levels they were at after initial course of vaccine; and with the quantity of vaccine that is being produced for world-wide use, it’s likely that the cost will be considerably lower in 15 years time.

Have you found this interesting? Have you got any information that may be relevant to the investigation? I am particularly interested in knowing which countries use which vaccine in their (perhaps non existing) vaccination programmes. We know that both vaccines have been approved in most countries, but which one do their governments pay for – and which one does private care tend to go for?

I’ve received many emails and tweets so far. They all have been very useful in my research. Please contribute as well by commenting this blog post!

satellite picture

Cervical cancer, an African disease

Cancer is usually referred to as a disease of the Western World, but the truth is cancer affects people in poor countries more than anyone else.

Cervical cancer is particularly prevalent in developing countries, which count 80% of the cases. In Sub-Saharan Africa, where sexual risk behaviour also counts for high rates of sexually transmitted diseases (STD), cervical cancer is the most common cancer in women.

I interviewed Professor David Kerr, who is the President of the European Society of Medical Oncology and established the Africa Oxford Cancer Foundation (AfrOx). The charity aims to improve the delivery of cancer care in Sub-Saharan Africa. He told me how cervical screening programmes are being implemented in African nations.

Débora Miranda – How much is cervical cancer a priority in the Afrox work?

Professor David Kerr

David Kerr – It’s a key priority. We know that cervical cancer is the commonest cancer in Sub-Saharan Africa and indeed the whole of the developing world. Therefore it’s desperately important that we develop strategies for prevention, screening, early detection and treatment. It affects women at an important stage in life, it leaves families devastated and therefore it’s a top health priority. If we started vaccinating all girls in Africa today that would have an impact of 20 to 25 years, so we need to develop strategies which are not solely dependant on vaccination, but allow us to take care of women who are at risk over the next two decades – and of course women who are presented with a disease for treatment. In a way you’ve got to be able to deal with the whole pathway of the disease.

I assume you have to develop strategies not on an African level but in each country individually. How does that exactly work?

Indeed. We are focused predominantly in Ghana. We have very good relationships with the Ghanaian cancer society, excellent relationships with the Ghanaian health ministry, and very good relationships with the doctors and nurses that work with the health service there. What we hope is that the model and the experience that we develop in Ghana will help the rollout in other African countries.

Why Ghana?

Three years ago Afrox held a meeting in London with 32 health ministers there. All of them wanted to work with us but the Ghanaian were the ones who wanted to work with us first. Ghana is important because they’ve got some important existing cancer infrastructure – many African countries do get nothing whatsoever, there isn’t a single pathologist for example – but in Ghana there were some kinds of specialists, there were two centres, so there was a platform to build from and we thought that was the place to start.

Is there any vaccination programme running there?

At the moment there’s not, but we Afrox have just put together a pilot vaccination programme which will take us across three of the large districts of Ghana. We’ve just agreed this with the Ghanaian health authority. We believe that we’ll be able to get free vaccines from the manufacturers to roll this out and we’re seeking funding from international donours to provide the infrastructure, the healthcare workers, distribution and awareness raising so we can actually deliver the vaccine. We’re seeking funding just now and we plan to start rolling this out in the final quarter of this year.

Which one of the vaccines is it?

At the moment we haven’t decided. Both the vaccine manufacturers have open access programmes and they are keen to support African health ministers and NGO’s in getting the vaccines. But that’s a discussion that we’ve yet to conclude with the Ghanaian health ministry.

Vaccination programmes work better if they are school-based. Isn’t this hard to achieve in African nations?

Again, you’re making an important point and you are correct. But in Ghana we’re in a very strong position because 90% of Ghanaian children attend school. So again it’s an ideal place to pilot school-based model.

Which African countries are best in tackling cervical cancer?

There are open access programmes for vaccines working on Nigeria, Uganda and Rwanda, allowing countries which otherwise wouldn’t be able to afford the vaccine. There are good examples of what’s starting to take place. But of course none of the African nations has a comprehensive  national programme because there’s no funding available to be able to roll it out at that level.

Even if the manufacturers agree to help these countries it probably won’t last forever; at one point governments might have to invest themselves. And a vaccination programme only works effectively in a long-term basis.

Yes, sustainability is key and clearly the pilot programme we’re putting together for three years will cover 20% of the Ghanaian population. What we hope is that by doing this work, by understanding how to deliver the vaccine and how to raise awareness and reach schoolgirls, learning from that will allow us to roll it out. We hope that the price of the vaccine will come down. We hope that the international aid community will support GAVI, the Global Alliance for Vaccines and Immunisation, to help provide the vaccine to those nations that require it. In the next few years we’re hoping and guessing there will be an international aid programme to make the vaccine more widely available.

What are the biggest challenges to tackle cervical cancer in Africa?

We know that cervical cancer is caused by the human papillomavirus and is very prevalent in African women. The main problem is, when patients present the disease it’s at a very advanced stage. This is a problem with cancer generally in Africa. By the time patients (if ever) present in a conventional health system, like hospitals or GP’s, the cancer is usually reaching a very advanced stage which is much less likely to respond to treatment. So I think not only must we do work in terms of vaccination and prevention, but awareness raising and thinking how we can bring in a screening programme even if it’s just once in a lifetime screening. That’s been shown to save lives and reduce the death rates. We’re working up a plan for that to see if we can get the disease at an earlier stage when it might be treatable, but at the moment the vast majority of women come with a massive burden of cancer that is often impossible to treat other than pine it with painkillers.

Does it also depend on the type of screening that you adopt? Prof Peter Sasieni from Cancer Research UK told me HPV testing will be much more efficient in the developing world because it is realistic in almost any laboratory. It won’t require the same skills that liquid based cytology does.

I would agree with that. There’s a company called Qiagen who have got a point of care who does the DNA test for HPV. There are trials that have been performed in India showing that doing a just one in a lifetime screen, not asking women repeatedly (because you can’t afford that) does definitely reduce the death rate from cervical cancer. I think there’s two innovations, one is the DNA test and one that says let’s just start with a once in a lifetime test.

But if you need to start a screening programme from scratch, isn’t HPV testing the best choice?

I think there needs to be a transition. If you’re working in Africa we need to convince our colleagues of the utility of the test, that we can deliver in a rural, village setting in Sub-Saharan Africa, that we can keep the tests safe (especially if it’s a warm climate), etc. So there will be a phase of transition because for those countries which have got cytology services I think we need to move from one to the other. But I agree that the future is likely to be the DNA test.

Call and recall system is important. In countries where transport system is not the best, isn’t this a challenge?

We’ve been working with a Professor of Gynaecology in Cardiff, Alison Fiander, and her colleagues in Ghana. They develop a one slot shot because a call and recall thing doesn’t work. If we bring women to have the DNA test and if we spot that someone has an early cervical lesion or an early cancer we think it’d be possible to treat those in the field – using devices that would allow to burn the cancer out, painlessly in a rural setting. This seems a much better way to go for us.

What partners does Afrox work with?

We work with the two major professional cancer societies: the European Society of Medical Oncology – I happen to be the president of that – and the American Society of Clinical Oncology. This gives us access to tens of thousands of cancer professionals around the world who are keen to work with us and to support these programmes. We work with the pharmaceutical industry, which does want to make a difference and see what they can do to support cancer improvement generally in Africa. We’re working with the civil society because perhaps the most important message of all is awareness of cancer. Working with the Ghanaian cancer society allows us to make deep routes towards citizens. In developing countries the health ministries are really important and they need to feel ownership of these programmes and they need to be part of this early on.

Does the developed world still have to realise that cancer is a big reality in developing countries?

We know that in Africa there are more than 200 dialects spoken and the vast majority for them have no word for the disease cancer. Most Africans still live in a rural setting which delays treatment – there’s very little that can be done for those women with cancer. This increases the degree of stigmatisation that cancer is not a word but rather a death sentence. There’s a lot of work to be done there.

To think about, even if not infected

“Until I had an abnormal smear test I never thought much about the screening programme.”

So far I have received many emails from readers of this project. Experts have shared their knowledge and research, whilst patients have shared their experience.

All patients who have contacted me have had some kind of personal experience related to cervical cancer, most being women with a history of abnormal smear tests. This shows, just like with other diseases, that unless it affects us or our beloved ones we are rather unlikely to engage in the debate. However, most of what these patients have told me should be of interest to the general public, especially young women. Here are some of those thoughts.

(Note: In order to protect the identity of the sources, I was asked to keep them anonymous.)

“Associating infection with sexual behaviour is unhelpful and stigmatising”, a woman told me. She had treatment for high grade cervical pre-cancer at the age of 33 and claims to have had two sexual partners with whom she has always used condoms. Her abnormal smear test came when she had been married for many years.

Do condoms protect against HPV? Credit: Wikicommons

Indeed, I wrote about the links between HPV infections and sexual behaviour, but it should be emphasised there is not one single way to prevent cervical cancer. Vaccines, smear tests, few sexual partners or use of condoms do not necessarily prevent the disease. To what extent would better health education and communication help tackle this problem?

In fact, “safe sex” is not enough, as many factors are associated with an HPV infection. Sexual intercourse is not the only way to transmit the virus; some of its strains can be transmitted through kissing. Most people will be infected in their lives, but in many cases our body’s immune system will be able to clear the virus without it causing problems.

Ironically, when it comes to vaccination this infection seems to be persistent, as most experts claim that a HPV vaccine doesn’t clear the virus if it has already been contracted. Again, HPV may not be as alarming as HIV, but shouldn’t there be more information about this virus?

Concerning HPV related cancers other than the cervix, let me share with you what a 31-year old Mexican man wrote me: “If I had taken the vaccine, I might have had my complete tongue by now”. He was 27 when diagnosed with tongue cancer. “In the biopsy we found HPV. The doctor asked me if I had had any homosexual intercourse, and the answer is no. I just have had one sexual partner, and that is my wife.”

His words reflect the need to clarify how HPV affects men. The fact that his doctor asked him about his sexuality may show that gay men are at increased risk of HPV-related cancers, however heterosexual men can develop these too. The number of sexual partners one has also does not necessarily determine how likely he or she will be infected with the virus. Many people become infected having had only one sexual partner – this partner might have had others though. But is it fair, or even useful, to let the rule of probabilities ruin the confidence between a married couple?

Prevention of cervical cancer in private healthcare can reach high costs. Credit: Grant Cochrane

A young woman from Portugal mentioned the financial costs associated with a HPV infection. In this project I’ve tried to discuss policies from different countries, therefore we should balance the weight of private healthcare services and insurance companies in other nations.

Upon being diagnosed with a HPV infection in her cervix, this 27-year-old Portuguese patient has paid more than €600 in the private sector for HPV testing, smear tests, other exams and dermatological treatment to her genital warts. She wonders whether the SNS (Portugal’s public healthcare system) would have prescribed her the same exams, how much of these costs would have been taken by the state, and how quickly she would have been treated otherwise. What is the situation like in your country?

When seeing these realities, one shouldn’t forget the UK has a National Health Service and an effective, public cancer screening programme. A British woman wrote me about her disappointment towards this programme, but she admitted not having had contact with health services of any other country.

The progress of science has allowed us to prevent and treat many diseases that people would have easily died of some years ago. It seems that the more we have, the more we expect; should we, journalists, make citizens wonder whether they are in the right to complain?

From The Guardian: Should boys be vaccinated against the human papilloma virus?

Deciding which HPV vaccine – if any – to use in a specific country requires financial, social and cultural considerations. My most recent blog post on The Guardian Science Blog discusses the question whether men should also be vaccinated against the virus.

A recent study has shown that most British doctors would give Gardasil to their own daughters – but the same question was not asked regarding their sons.

I provided information about cancers other than the cervix, which are also linked to the human papillomavirus – and which often occur in men, such as anal cancer.

Another question to consider is what can be done to protect homosexual men, given that they don’t benefit from the herd immunity acquired by vaccinated women.

Finally, I write about the effect that sexual behaviour has on HPV infections.

You can find the story here. Have you done any research on this topic? Please add your knowledge to this discussion.

From The Guardian: How do you choose the best vaccination against cervical cancer?

My thoughts on the balance between both HPV vaccines have been published on The Guardian Science Blog.

I wrote about the relevance of genital warts in young people and how the choice of a vaccine could have a cultural dimension.

I also clarified why the UK Government didn’t follow the recommendations made by the Joint Committee on Vaccination and Immunisation (JCVI) to adopt the Gardasil vaccine, going for Cervarix instead.

Once you read it here, I challenge you to come back and share a comment!

Men at “increased risk” of HPV

When I interviewed Dr Anne Szarewski, a clinical consultant at Cancer Research UK, she raised interesting points with regards to the effect that HPV has on men. Ideally, she would vaccinate all the boys with Gardasil and all the girls with Cervarix. Listen to this bit of our interview to find out how and why.

Audio transcript
Anne Szarewski – I’ve always been extremely in favour of vaccinating men for so many reasons. First of all I think on a public health equality basis I think it’s almost outrageous that we actually put all the burden as though it’s only women who transmit a sexually transmitted virus. On a public health message that is just wrong. Secondly, if we don’t vaccinate men then of course the men who have sex with men get nothing because they cannot benefit from the immunity from women, that’s impossible. So we just ignore them. Of course they are at increased risk: anal cancer, penile cancer, genital warts (obviously for them you would use Gardasil I’ve never suggested using anything other than Gardasil for men). I really do believe we should be vaccinating both. And of course now that the evidence is getting stronger for head and neck cancers, all these non-genital cancers associated with HPV, then again the message gets stronger to vaccinate men.

Débora Miranda – But as it is now your position is that the priority should be vaccinating women with Cervarix.

AS – I would not be averse – and I think it could be done – that we could actually vaccinate all the girls with Cervarix and all the boys with Gardasil. I don’t think this is impossible. What would I think then need to be done is they would need to come to an agreement that probably you would stretch the Cervarix schedule to make that 0, 2 and 6 months. I suspect that the Cervarix schedule (it would have to be done in agreement with the companies and everything), but I suspect that the Cervarix schedule could be stretched to become 0, 2 and 6 months so that it would be in line with the Gardasil schedule – and then you would not have a problem of the girls being vaccinated at a different time to the boys. So you would have to make a change, but I think that would be a change that was worth doing. And you wouldn’t mess up the follow-up of the girls because they would still be getting Cervarix.