Sunday, November 15, 2009

Cervical Cancer: A Personal Journey


By Jennifer O'Connell


It is a gloomy afternoon in December 2005, and I am sitting in a small, strip lit room in an office in south Dublin. This is the kind of place in which every woman hopes never to wind up. It is sparsely furnished: two chairs, a desk and a surgical bed with stirrups at an implausible distance apart.


Sitting opposite me is a sympathetic gynaecologist.


‘‘Whatever you do," she tells me, ‘‘don’t get pregnant before your next appointment."


In this setting, with my recent medical history, the prospect seems so implausible that we both laugh.


More than ten years of abnormal results in my smear tests have led me here. Now, after yet another result indicating precancerous changes around the neck of my womb, my GP has referred me on for further treatment - a colposcopy, or an internal examination under a microscope, and - depending on what this throws up - possibly a LLETZ procedure, in which the area of abnormal tissue is removed completely, or a cone biopsy, which does the same thing, only more invasively.


Fast-forward two weeks. I am back, stripped down to a hospital gown and preparing to navigate the impossible distance between those stirrups.


Despite my assurances that I’m definitely not pregnant, my gynaecologist thinks she’d better ‘‘have a quick peek’’ before she performs the colposcopy.


And there, floating around on the screen, is the 8mm long, seven-week and five-day old blob that will become my daughter.


Throughout the following months, while I was busy growing a baby, I was only occasionally aware of the other, less welcome lodger in my womb: the minuscule precancerous cells that might, I knew, be growing and multiplying alongside my future child, fuelled by all those extra hormones.


By the time I finally got around to that colposcopy, leaving my three-month-old baby with her father in the waiting room outside, it did indeed seem that she wasn’t the only one who’d had a growth spurt.


Whereas I initially had what was described as ‘mild-moderate changes’, I now had a high-grade lesion, technically known as CIN stage 2/3. As the gynaecologist explained with her hand resting kindly on my prone knee, this meant my condition was just a step away from being cancerous.


Thankfully, I was one of the lucky ones. During the colposcopy, my gynaecologist performed a cone biopsy, which removed the troublesome cells.


My next two smear tests showed up normal.


I was finally free of the spectre of cervical cancer that had been hanging over me for most of a decade.


During the 14 years since I had first been diagnosed with a low-grade human papillomavirus (HPV) infection following an abnormal smear, our understanding of what causes cervical cancer has improved beyond all measure.


Back then, as a nervous 20-year-old,my only source of information was an ancient copy of Our Bodies, Ourselves in the college library. Unsurprisingly, the book didn’t mention HPV, the virus that we now know causes all cervical cancers. The section on smear tests outlined only that they were the best possible way to detect the cellular changes that can lead to cervical cancer. The internet was a mere neonate,Amazon.com just a business plan, and I had nowhere else to go for information. So I took the antibiotics the doctor prescribed, and tried to forget about it.


The year was 1995.At exactly the same time as I was furtively consulting the original feminist bible in the back of the Lecky Library in Trinity College, scientists were making the first incontrovertible link between HPV and cancer.


What has been achieved in the years since is unprecedented in the history of cancer research.


In the time it took me to leave college, get a job, get married and have babies, scientists managed to pinpoint the cause of the second most prevalent cancer among women; pioneer large-scale education programmes around the world; create not one, but two vaccines against the primary cause of this cancer; and implement immunisation programmes which will potentially spare future generations of millions of women from what remains, despite the medical advances, a truly horrendous way to die.


Even more remarkable is the fact that every single step towards the creation of these vaccines represented, as the New York Times put it in 2006, ‘‘a triumph of hard science over the pseudoscientific myths that for centuries surrounded the disease’’.


The story behind any major medical breakthrough is almost always an interesting one in its own right. But the journey that had led scientists to this point is particularly colourful, featuring many blind alleys, cutthroat professional competition, rabbit horns, a soup made of caterpillar ovaries, a group of helpful nuns, and one man’s enduring fascination with cows’ warts. Cervical cancer has always been one of the least understood, and most stigmatised, of cancers. A clue to why lies in the observation, as far back as 1842, by a doctor in Florence who noticed that, while prostitutes and married women got cervical cancer, nuns almost never did.


He might have made the obvious - and correct - assumption that cervical cancer is sexually transmitted, but he was thrown off by something else. Nuns often got breast cancer, which tended to kill them first. So he concluded instead that nuns’ corsets were dangerously tight, and failed to pursue the origins of cervical cancer any further.


Almost 60 years later, doctors at Leeds General Infirmary noticed, as the subsequent article in the Lancet put it, that cancer of the cervix ‘‘was seldom or never met with among the numerous Jewesses’’.


Later, this would give rise to one of the many, many myths about cervical cancer:


that circumcision of the male partner offers protection from it.


At the time, though, the writer didn’t even get that far: he thought salt caused cancer, and concluded that avoiding bacon was what protected the Jewish women in his study.


It was the 1970s before American researchers again came tantalisingly close to the discovery that cervical cancer was essentially a sexually transmitted disease. They noted that women who suffered from it often had a history of genital herpes. But instead of drawing the conclusion that both conditions occurred in women who were sexually active, they concluded that it was the herpes virus which caused cervical cancer. And off they skipped down what would prove to be yet another blind alley.


Meanwhile, a German researcher was nudging closer to the truth, using work done in the 1930s by Dr Richard Shope, the then head of Rockefeller University in New York, on - of all things - rabbit horns.


Shope was on a hunting trip with friends when he got wind of rumoured sightings of rabbits with horns. Fascinated, he asked his friends to send him some of the horns, which he proceeded to grind up and filter through porcelain. He injected this filtrate made of virus-sized particles into other rabbits, which grew horns in turn.


The ‘horns’, it seemed, weren’t horns at all, but very large warts. He believed they were spread by a virus.


Shopes’s work on the ‘rabbit horns’ spurred a German scientist, Dr Harald zur Hausen, to explore the virus hypothesis. As early as 1976, he published the hypothesis that human papillomavirus played a part in the development of cervical cancer. However, it wasn’t until the advent of DNA magnification in the 1980s that he was able to pursue this avenue in earnest - work that would eventually win him the Nobel Prize for Physiology or medicine in 2008.


Papillomas (warts) affect many animal breeds, from whales to birds. More than 150 strains, and possibly up to 200, exist of the human papillomavirus. Many of them are apparently completely harmless; others cause warts on the hands or face; others cause genital warts.


But one annoying little fact continued to prove a stumbling block throughout the frantic decade of research that took place in the 1980s.Humanwarts actually contain very little papillomavirus - not nearly enough to make large-scale studies feasible.


An American scientist at the University of Rochester, Dr William Bonnez, hit upon a cunning solution. Dairy cows, he knew, grow warts the size of grapefruits. He pestered veterinary surgeons to donate their cow warts to his research, and eventually stocked up several freezers’ worth.


Next, he needed a group of humans who had never had sex to participate in his study - which is where the nuns come in. The Sisters of St Joseph of Rochester were ‘‘really very supportive’’, Bonnez would later tell the New York Times, agreeing to answer questionnaires about their sexual histories and to give blood samples.


Once the link between the human papillomavirus and cervical cancer had been established beyond all doubt, creating a vaccine for it was only a matter of time.


Compared to the haphazard and occasionally medieval-sounding research that had led to this point, the vaccines are manufactured using processes which might have been dreamed up by the makers of Alien.


Merck’s vaccine, Gardasil, is made from a yeast that grows the proteins which form the outer shell of the virus. The proteins grow in batches of 360; each batch magically assembles itself into a ball, precisely the shape of the shell.


Cervarix, GlaxoSmithKline’s rival vaccine, is produced in a insect virus concocted in a broth made of caterpillar ovary cells.


If they were implemented worldwide, these vaccines would have the potential to virtually wipe out strains 16 and 18 of the HPV virus, which are responsible for 70 per cent of cervical cancers. The other 30 per cent are caused by other, less common variants of HPV.


Gardasil’s more expensive shot also offers protection from the two strains that cause genital warts.


But all this applies only if enough young women have access to them. And that’s the other thing that makes the story of cervical cancer, HPV and the vaccine unique.


The development of a vaccine for any cancer is unprecedented. With the exception of the Hepatitis B vaccine which can prevent the development of liver cancer, there is no other immunisation against cancer.


But also unprecedented is the speed at which it has made the leap from much vaunted medical innovation to must-have shot to political football.


As with all vaccines, immunisation against HPV will only work when a large enough proportion of the population has access to it. And as with all newly-minted vaccines, it is expensive - to have it done privately costs between €390 and €600.This is why health campaigners push so hard for state-sponsored schemes.


Already, it is in available in nine European countries free of charge. Two more - Belgium and France - offer it on a subsidised basis. In each of these countries, especially those offering schools-based programmes, the take-up has been good.


But there have also - perhaps inevitably - been road bumps along the way.


In Britain, one of the countries which offers a schools-based programme, the sudden death of an apparently healthy young woman, Natalie Morton, within hours of getting her vaccination last month sparked a rash of negative and ill-considered publicity about the so-called ‘cancer jab’.


Parents suddenly questioned the wisdom of allowing their perfectly healthy young teenagers to avail of a vaccination for a condition that might or might not strike them at some indeterminate point in the future.


Within days, it was clear that Morton’s tragic death had nothing whatsoever to do with the immunisation - the postmortem revealed she was suffering from a previously undiagnosed tumour in her thoracic cavity.


As the Irish Cancer Society (ICS) puts it, ‘‘it was purely a very unfortunate coincidence’’.


But the tabloids which had splashed news of her death ‘‘following the cancer jab’’ across their front pages were markedly slower to report that it was, in fact, entirely unconnected.


In Ireland, the controversy about the jab, which has been simmering away for exactly a year, is nothing to do with the non-issue of vaccine safety: at one death for every one million vaccinations, the HPV jab ranks as very safe indeed.


In September 2008,Minister for Health Mary Harney announced that she would be following the advice of a Health Information and Quality Authority (Hiqa) report and implementing a free vaccination programme for girls aged 12,with a catch-up programme to follow.


Two months later - a year ago last week - she announced that the programme, which would have cost around €10 million, was cancelled due to the economic crisis. The money would be spent instead on the screening programme which, she argued, was 100 per cent effective, compared to the vaccine’s 70 per cent efficacy.


‘‘It doesn’t make sense," says Meghan Doherty of the Irish Family Planning Association (IFPA). ‘‘Not from a health point of view, and not even from a financial point of view. The vaccine is expensive, but so is treating people in all stages of pre-cancer and those invasive cancers.


‘‘If we only take the 12-year-old girls, it would cost a little less than €10 million for a schools-based programme. But in the long term, over a 70-year period, that would save the government about €2.74 million in avoiding treatment for people who would otherwise go on to develop Cin 1, Cin 2 and Cin 3 abnormalities, and invasive cervical cancer.


‘‘That’s according to the government’s own figures, taken from the Hiqa report of February 2008. It would also save around 52 lives a year. Yes, screening is extremely effective in picking up pre-cancer at an early stage, but the vaccine could prevent 70 per cent of those pre-cancers from developing. It shouldn’t be an either/or." The other consideration is the emotional cost.


‘‘That’s not a side of the debate that gets much airing, but there’s huge stress and inconvenience involved to women who go through the process of having one or more abnormal pap smears," says Philip Davies of the European Cervical Cancer Association.


‘‘Then you have to take into account all the time these women are not going to be in their job, the emotional cost on her partner or family. These are all things that the €10 million doesn’t capture."


But if there’s anything good to be gleaned from this virtual overnight volte face, it is that there can now be few people in the country who haven’t at least heard the term ‘cervical cancer’.


‘‘From a public awareness point of view, it has been helpful," Doherty says. ‘‘Last September, the national cervical cancer screening programme started up. A couple of months later, the controversy kicked off here about the vaccine, and then a few months later, Jade Goody’s awful death from cervical cancer was getting all that coverage in Britain and here. All of that combined to bring about a huge increase in the number of people taking up appointments to have a smear. It has been helpful in raising awareness." But we still have a long way to go. Despite the dizzying pace of the medical advances, the ‘pseudoscientific myths’ the New York Times was writing about three years ago have been hard to shake.


During the ten years that elapsed between my first abnormal smear and my first colposcopy, I read everything I could find on cervical cancer and HPV, but the information was sparse, confusing and often contradictory. At different times, I read that cervical cancer was 100 per cent sexually transmitted, and so you didn’t need to worry about it unless you were promiscuous.


I read that circumcision prevented it; that Jewish people were immune from it; that mostly older women were at risk; that you were at a higher risk if your mother had it; that genital warts caused cervical cancer; that if you’d had genital warts, you couldn’t get cervical cancer.


With the exception of the fact that it is sexually transmitted, every one of these statements is wrong or dangerously misleading.


And the confusion persists. Just last week, in my research for this article, I asked one professional working in the area of women’s health about exactly what the link is to genital warts - if you’ve had warts, are you less at risk, or more at risk? She didn’t know the answer.


In fact, there’s no connection. Genital warts are caused by a strain of the HPV virus that does not cause cervical cancer. But just because you’ve had one strain doesn’t mean you can’t get another.


If confusion still exists among those working in the area, it puts some perspective on the findings of a study carried out by vaccine manufacturer GlaxoSmithKline in 2008,which showed that three out of four women still don’t know what causes cervical cancer.


All the experts I interviewed agreed on one thing. Of all the many, many misconceptions and myths that prevail about cervical cancer, the most common is also possibly the most damaging.


‘‘The biggest misconception? People do not understand that almost everybody who is sexually active will have an HPV infection at some time in their lives," says Davies.


‘‘HPV is everywhere. Thirty per cent of women will have it after their first partner; 50 per cent will have it after their second partner.


And they’re just the rates that we have detected - in reality, it’s probably much higher. It is not an indication of sexual promiscuity, not by any means.


‘‘The other thing people don’t get is that the vast majority of HPV infections will disappear on their own. If they happen to have a Pap smear at the same time as they have a HPV infection, they will get an abnormal result, but it will usually clear up by itself by the time the follow-up smear comes around."


Alison Begas, chief executive of the Well Woman Clinic, says the majority of women coming into her organisation’s clinics have little knowledge of HPV.


‘‘Every sexual encounter carries a risk of it - you don’t even have to have intercourse. Within the first 18months of our first sexual encounter, the vast majority of us will get HPV," she says.


Like Davies, she is at pains to point out that it is usually harmless, and that most of us will fight it off with it with no adverse effects - in adolescents, 90 per cent of HPV infections, along with 75 per cent of those in adults, resolve without treatment.


‘‘Cervical cancer is very slow to develop, which makes it very easy to treat in the early stages. For the most part, you’d be looking at 10-12 years before cellular changes turn into cancer, and that’s the reason that, even in people who have been vaccinated, we advocate getting regular smear tests."


Doherty points out the importance of educating women - young women especially - about the risk factors. ‘‘The earlier you have sex, the more at risk you are, as your cervix hasn’t developed. There’s a lot of confusion out there among young women - we’ve had them tell us they thought that if they washed a lot, it would go away."


Perhaps even more dismaying are the results of research conducted by the Irish Cancer Society in 2006 on public awareness and attitudes to cervical screening and cancer.


One of the most common misconceptions was the belief that ‘‘cervical cancer is hereditary and/or caused by multiple sexual partners and/or a ‘bad’ lifestyle’’.


Davies points out that we have all been on a steep learning curve when it comes to cervical cancer.


‘‘It’s not surprising there’s confusion, when you consider that the link between HPV and cervical cancer was only really well-established by 1995," he says.


‘‘We’ve only had 14 years to get the message across. The smoking campaign - and that is a much less complex message - took 30 years, so by that measure we’re probably doing okay."


For information or advice on any aspect of cervical screening, and/or cervical cancer, call the National Cancer Helpline on 1800-200700


This article first appeared in The Sunday Business Post on Sunday, November 15, 2009





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