By Grant Jacobs • 11/05/2018 • 22

When the author and the core claims of the paper aren’t real, you’re faking HPV vaccine claims in more ways than one.

A new paper in the Indian Journal of Medical Ethics (IJME) claims that the HPV vaccine causes an increase in cancers in some patients. It’s first problem is that the author is fake.

A fake author

Yes, you read right. (There’s irony, too, seeing this in a journal about ethics.)

Several sources—including the Skeptical Raptor and Retraction Watch—highlight that the author faked their name. The author claimed to be a Lars Andersson hailing from the Department of Physiology and Pharmacology of the distinguished Karolina Institute in Sweden. The department says that they have no Lars Andersson.[3]

Amazingly, the journal acknowledges the author faked his name, but has decided it is OK for him to continue with it.

This is bizarre. Scientists write under their own names. In 30+ years of reading science I don’t know of a single paper written under a fake name.[4] I doubt many journals would accept it. But this journal seemingly casually accepts this as if were normal practice. Strange stuff indeed.

Also it’s a precious argument. As the Skeptical Raptor said, “What a snowflake!”

Take our resident vaccinologist, or any scientist working on topics a few people rail against. They don’t publish under false names, and some of the abuse they receive is awful.

It matters other ways, too. We’re usually able to see the author’s previous work, their skills, and so on.

It’s a fairly easy guess that the actual author has little genuine experience in the field as the paper has huge bloopers.

Also easy to easy to guess is the author’s sympathies: at least one of the references is from an anti-vaccine website.[5]

More papers under the fake author

Checks online reveal several other papers using this name from the same department. Since there is no Lars Andersson at this department, these too must be publications under a fake name.

Three are at the lowly Journal of Internal Medicine, one at the reputable Vaccine.

Micheal Head says the editor of Vaccine is investigating. I can’t read the paper in Vaccine: it is pay-walled. There is a reply to his letter to Vaccine. Part of this has been tweeted; his plate was politely handed back to him,

The use of ‘crude rates’ strikes a chord. The same is true in the IJME paper we’re looking at here. Those in science will recognise it as a gentle poke at the naïvety of the ‘analysis’.

The Karolina Institute is also investigating. (Original.)

Peer review-free opinion piece?

The article is a ‘Comment’ piece. It may be that these are not peer-reviewed. If so, it’d be free-form opinion. If it was peer-reviewed, you’ve got to worry about the state of the peer-review as it’s full of holes. Either way, you might worry about the state of editorial decisions. You’re left wondering if the journal is just in for the money.

The main claims over-reach and miss the simple answer

The paper’s main claim is that there is an increase in cervical cancer starting from the around time the vaccine was introduced. It’s based on overly simplistic presentation of previously published statistics, one that misses (or hides) that it’s mostly looking at unvaccinated people. There’s no new data, just an interpretation with obvious flaws.

This paper tries to play a speculative idea. It fields the notion that the vaccine ‘promotes’ cancer in women who already have an HPV infection. (They write “disease enhancement”). The author argues that this might be from the vaccine re-activating viruses already present. That’s an hypothesis, an idea, and not a new one. It’s not a finding, a conclusion. It tries to argue that it might happen by pointing at an increase in reports of cancer or pre-cancerous cells.

When we look closer, there’s a much simpler explanation: most of these women are not vaccinated. This means it can’t be the vaccine causing this claimed increase in cancer: they’re not vaccinated. It may also be partly that better screening misses fewer cases. (No increase in cancer, just more cases ‘caught’ earlier.)

This paper is looking for a complex answer where a simple one does better. (Which is a very polite way of saying the paper is making an ass of itself.)

Let’s first refresh what the vaccine does before looking at what the paper gets wrong. (Time permitting I’ll show the details in a follow-on piece; here I want to keep it simple.)

What the vaccine does

Human papillomavirus (HPV) infections are mostly passed on by sexual contact.

Infection with the virus can create pre-cancerous cells, some of which will later go on to form cancers.

The vaccine aims to prevent HPV infection from ever happening. This ultimately prevents the cancers from happening too.

Vaccinating women already infected with HPV doesn’t change the likelihood of cancer from the HPV strains the vaccine covers much. It shifts the odds the a little, but doesn’t eliminate the odds or reduce it much.

By contrast vaccinating before infection nearly completely eliminates infection and pre-cancerous cells. It’s important to get vaccinated before catching an HPV infection.

Hence the vaccination programs focus on vaccinating before people are sexually active. It’s also a reason that there is little effort to vaccinate past their youth.[6] HPV infections are very common; most older people are already infected.

In fact, the vaccine is so effective that potentially we could eliminate the cancers HPV causes entirely. More on that towards the end, in the section A better paper.

Measuring progress towards cancer

There’s catch to cervical cancers studying younger women: they generally don’t have the cancer yet as it takes years to develop.

Science comes to rescue. You can measure if a patient has the pre-cancerous that might later go on to form cancers. Measuring these pre-cancerous cells can substitute for measuring the cancers in younger people.

Let’s now look at the main problems in this paper.

They’re not vaccinated

The first, and main one, is that the increase in cancer noted in the paper are in women who are not vaccinated.

It can’t claim the vaccine increases cancer rates if the data it uses are people who ar not vaccinated.

The paper notes rates of cancer in women aged 20-49 in Sweden.

Trouble is, all but those aged 20-23 are not vaccinated.

Others have pointed out women older than 26 in Sweden were not vaccinated. The first comment at Retraction Watch quotes Joakim Dillner of the Karolina Institute, a specialist in tumour virology:

But data up to 2015 are very clear, as stated in the NKCX Annual Report for 2016. Vaccination is recommended up to 18 years. In Stockholm and Skåne they had an offer of vaccination up to 26 years. But above 26 years, there is basically no one who vaccinates.

Even the paper itself says the oldest vaccinated women in the study were aged 23. So of the aged 20-29 group, ages 24-29 are not vaccinated, and none of the women aged 30-39 or 40-49 were vaccinated.

Almost the entirety of the increase in cancer reported are from women who have not been vaccinated. If not the entirety. It’s entirely possible that the cases in ages 20-23 are from those who didn’t get the vaccine too.

The rates of cancer are in younger women are very rare

That graph uses data about rate of invasive cancer in different regions of Sweden. Note that’s cancer, not detecting pre-cancerous cells. These cancers take many years to develop. They are very rare in younger women.

By presenting paper the rates of invasive cancer the paper hides that the actual number of cases are tiny. The argument offered ultimately rests on just 2 or 3 cancer cases. You can’t conclude anything from that.

On top of that, all but a couple of the regional increases in cancer are statistically too weak to use.

Better screening ‘catches’ more cases sooner

Another problem is slightly more subtle. One way you see get an increase in reported cases is if a better effort is made to find them. Basically: no actual increase in the incidence of cervical cancer (or the pre-cancerous cells), just that you’re missing fewer of them.

Skeptical Raptor has covered this, and I’ll encourage you to read his take on this,

… cervical cancer incidence increased as a result of more screening, which is an independent variable that has nothing to do with vaccines.

It’s relevant point, but I think it’s less important here. The paper is already a wash for the reasons I’ve outlined above.

Citing an anti-vaccine source

You’d think it couldn’t get worse, but, amazingly, reading further it does! A key reference the paper cites looks to be a draft of a FDA report, hosted on a German anti-vaccine website. If true, that’s the sort of thing we’d expect on suspicious websites, not in a scientific journal paper.

The final published report is available for anyone to use. It’s not hidden. More on this in follow-on posts.

What about editorial standards?

Aside from these issues that make the paper at very kindest dubious, all this raises questions about selection of papers at this journal and their standards.

The journal is a medical ethics journal, not a medicine journal. Despite this we see several papers on HPV that don’t look (to me) like ethics papers. Why are they publishing these? Most journals reject papers outside of the scope they cover, and quite firmly. One reason is to match papers to their peer review and editor’s expertise. If it was reviewed it’d be interesting to know who reviewed this paper,[7] and what their expertise was.

Either way, the call falls on editors. This paper has major, major bloopers. Bloopers so large I find it difficult to call it a ‘paper’ with a straight face. And that’s not mentioning that it fails to put the arguments present properly in context of other studies.

Conclusion, and where next

You’d want to say that this paper is on the way to retraction. Trouble is, they could have done it when they learnt the author faked their name. It’d have been an obvious prompt to check that the paper is sound. Goodness knows why they didn’t do it.

The IJME is going to receive a lot of mail pointing out terrible this paper is. There’s very little reason to keep it, it’s got just too many serious, basic flaws.

Authors of better efforts at the journal will no doubt express concern. The journal looking bad will cast doubt on their work, too.

You’d think these things are best dealt with promptly. Let’s hope for better, even if I’m not going to put money on that.

A better paper

A major study just out reports on the safety and effectiveness of the HPV vaccine. This one is sound. (Cochrane report page here.)

A systematic survey of 73,428 women pooling 26 studies looked at protection against pre-cancer in studies that compared the HPV vaccine against a dummy vaccine (a placebo). Most of the women were younger than 26.

Effectiveness

For younger women with no high risk HPV infection (ages 15-25), the vaccine strongly reduced the risk of cervical pre-cancer associated from 164 in 10,000 women to 2 in 10,000 women, with high statistical certainty. The vaccine also reduced any precancer from 287 per 10,000 women to 106 per 10,000 women, again with high statistical certainty.

For women free of the main two HPV strains (what the vaccine mainly targets, strains HPV16/18), the effect of the vaccine differs in different age groups,

In younger women, HPV vaccines reduce the risk of precancer associated with HPV16/18 from 113 to 6/10,000 women (high certainty). HPV vaccines lower the number of women with any precancer from 231 to 95/10,000 (high certainty). In women older than 25, the vaccines reduce the number with precancer associated with HPV16/18 from 45 to 14/10,000 (moderate certainty).

Some of the women who get the vaccine already have an HPV infection. (It’s what the shonky paper plays on). The survey also looked at all women, with or without HPV infection,

In those vaccinated between 15 to 26 years of age, HPV vaccination reduces the risk of precancer associated with HPV16/18 from 341 to 157/10,000 (high certainty) and any precancer from 559 to 391/10,000 (high certainty). In older women, vaccinated between 25 to 45 years of age, the effects of HPV vaccine on precancer are smaller, which may be due to previous exposure to HPV. The risk of precancer associated with HPV16/18 is probably reduced from 145/10,000 in unvaccinated women to 107/10,000 women following HPV vaccination (moderate certainty). The risk of any precancer is probably similar between unvaccinated and vaccinated women (343 versus 356/10,000, moderate certainty).

Adverse effects

The study checks for adverse effects, finding that,

The risk of serious adverse events is similar in HPV and control vaccines (placebo or vaccine against another infection than HPV (high certainty). The rate of death is similar overall (11/10,000 in control group, 14/10,000 in HPV vaccine group) (low certainty). The number of deaths overall is low although a higher number of deaths in older women was observed. No pattern in the cause or timing of death has been established.

Pregnant women

Pregnancy outcomes were also considered.

HPV vaccines did not increase the risk of miscarriage or termination of pregnancy. We do not have enough data to be certain about the risk of stillbirths and babies born with malformations (moderate certainty).

Lack of data is not a sign that something is wrong, just that there is no formal data scientists can present. (Put another way, there’s no data either for or against.)

There is NZ data covering some of this. The NZ work found that “prior vaccination with HPV vaccine had a significantly reduced risk of preterm birth”.

Edit: Since I wrote this post, Helen Petousis-Harris, Sciblog’s resident vaccinologist who currently sits on the World Health Organization Global Advisory Committee on Vaccine Safety (GACVS) and the International Brighton Collaboration Science Board, has written a comment (below) pointing out that,

There is actually some really good data on this. For example >92,000 pregnancies followed in the US Vaccine Safety Datalink, and a cohort study from Denmark of 540,000 pregnancies.

Overall conclusions

They conclude,

There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and women who are vaccinated between 15 and 26 years of age. The protection is lower when a part of the population is already infected with HPV. Longer-term follow-up is needed to assess the impact on cervical cancer. The vaccines do not increase the risk of serious adverse events, miscarriage or pregnancy termination. There are limited data from trials on the effect of vaccines on deaths, stillbirth and babies born with malformations.

The point about the impact on cervical cancer is that this work measures pre-cancer. It doesn’t directly measure how reducing pre-cancer translates to reduction in cervical cancer. It will be expected to, but there is no direct measurement of that yet.

Other articles on Code for life

A few vaccine resources (mostly for those wanting shorter overviews)

Sources for medical information for non-medics and non-scientists (for those wanted more detailed information)

If presenting a claim on a popular issue… “… consider testing if your idea is sound first” – some thoughts and advice on checking stuff out

Sources for medical information for non-medics and non-scientists (a resource page)

Fact or fallacy, a survey of immunisation statements in the print media (at the time I wrote that the media unfortunately get things wrong, which can be confusing if you’re new to the topic, but I have to say the NZ media is doing better of late — keep it up!)

The Panic Virus (a review of a book examining parents’ concerns about vaccines)

Thoughts on, and for, those trying to choose to vaccinate or not (Some thoughts on some aspects of parent trying to find sound information.)

Immunisation then and now (a peek at history)

Rubella, not a benign disease if experienced during early pregnancy (including rubella in New Zealand – I’m a rubella kid)

Footnotes

There are Lars Anderssons in other departments at the Karolina Institute. I don’t wish to bother these people who share a common name. I know of a scientist who included his two young daughters as authors, who he clearly loved. Rumours are, of course, rife. It’s fun in it’s own way, but I’d rather leave that alone. I’m defining youths are younger than mid-20s. Your mileage may vary! As an aside, in this online profile the editor of this paper describes herself –

Sandhya Srinivasan is a Mumbai-based journalist and researcher with master’s degrees in sociology and in public health. She has been a journalist since 1986. She was earlier executive editor and now consulting editor of the Indian Journal of Medical Ethics. In her pieces in the IJME, she describes herself as ‘Independent Journalist’. See for example in this piece by her in the IJME. Older pieces in IJME suggests hits is the description she has used for some time. (Shouldn’t she be declaring she’s a consulting editor of the journal she’s presenting herself as an ‘independent journalist’ in?)

Featured image

Electron micrograph of human papilloma virus. Public domain image, source Wikimedia. The virus particle is negatively-stained; the background is stained not the specimen. The result is an image that looks a bit like the film negatives of film era photography. (Film photography is still around, but now only practiced by enthusiasts.)