Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c712 (Published 02 March 2010) Cite this as: BMJ 2010;340:c712
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Jo Waller appears outraged that people might be misled by the
apparently misleading title of a research paper on the potential risks
associated with the HPV vaccine.
Given the recent retraction of a simple case series report [1] that
warned of a possible link between the MMR and an autism-bowel syndrome, I
now understand how the public – and medical professionals - can be swayed
by academic misinterpretation of such an early warning.
Professor Trisha Greenhalgh wrote an acclaimed book on the science of
trashing papers. [2] Jo Waller and Professor Jane Wardle may be aware that
in April 2004 their academic colleague at UCL scientifically trashed the
paper by Wakefield et al. [3]
The paper did not state a research hypothesis so Professor Greenhalgh
invented one. She then went on to state that the study design – a
descriptive report on only 12 children – was incapable of proving the
hypothesis that had never been stated. Knowing that the case report lies
at the bottom of the traditional hierarchy of evidence was why Wakefield
et al stated,
“We did not prove an association between measles, mumps, and rubella
vaccine and the syndrome described.” [4]
I write merely to express my concern that people may have been
misled.
[1] Lancet retracts Wakefield’s MMR paper. Clare Dyer BMJ
2010;340:c696, doi: 10.1136/bmj.c696
http://www.bmj.com/cgi/content/full/340/feb02_4/c696
[2] Trisha Greenhalgh. How to Read a Paper: the basics of evidence-
based medicine. BMJ Publications, Third edition 2006.
[3] Professor Trisha Greenhalgh. Analysis of Wakefield MMR study asks
why flaws weren't spotted by Lancet editors. April 2004.
http://briandeer.com/mmr/lancet-greenhalgh.htm
[4] Early report. Ileal-lymphoid-nodular hyperplasia, non-specific
colitis, and pervasive developmental disorder in children. A J Wakefield,
et al. THE LANCET • Vol 351 • February 28, 1998 637.
http://www.theoneclickgroup.co.uk/documents/ME-
CFS_docs/The%20Wakefield%20Paper,%20THE%20LANCET,%20Vol%20351,%20February%2028,%201998.pdf
Competing interests:
None declared
Competing interests: No competing interests
We are writing to express concern about the title of this research
paper: ‘Risk of miscarriage with bivalent vaccine against human
papillomavirus (HPV) types 16 and 18’. The way the title is phrased could
be interpreted to mean that there is a risk of miscarriage associated with
the vaccine, when in fact the findings are the opposite. We note that the
paper is already in the top ten ‘most shared’ articles on the BMJ website,
and we feel very strongly that in an era where scientific research is so
easily accessible to the public, every attempt should be made to ensure
that the findings are not misinterpreted by people who may not read much
more than the title.
Given the recent history of attitudes to vaccination, particularly
the MMR vaccine, we know that public opinion can easily be swayed by
misinterpretation of research findings. While it is vital that adverse
events associated with vaccination are clearly communicated, it is equally
important that when data are reassuring, these findings are communicated
as clearly as possible. A Google search for ‘HPV vaccination and
miscarriage’ yields over 31,000 results, many of which suggest that the
vaccine may increase miscarriage risk. The search result heading for
Wacholder et al’s paper reads ‘Risk of miscarriage with bivalent vaccine
against human…’ and underneath: ‘In secondary descriptive analyses,
miscarriage rates were 14.7% in the HPV vaccine arm and 9.1% in the
control arm in pregnancies that began within three ...’. On a quick look,
this could easily lead to the belief that miscarriage was more common in
the HPV vaccine group.
Perhaps it is time to reconsider the way in which the titles of BMJ
articles are constructed to ensure that they accurately reflect their
findings.
Competing interests:
We have, in the past, received funding and honoraria from Sanofi Pasteur MSD and GSK, both of whom manufacture HPV vaccines
Competing interests: No competing interests
Re: Misleading title II?
I suspect the semantic concern over the title of the paper by
Wacholder et al reflects considerable anxiety about the safety of the HPV
vaccine. Jo Waller and colleague will therefore be relieved to know that a
prominent result in a Google search for “HPV vaccination and miscarriage”
now puts a very positive spin on the results of this study.
Jim Glare, writing for the National electronic Library for Medicines
(NELM) news service, has positively summarised the paper under the Google
title, “Bivalent HPV vaccine does not significantly increase risk of ...”
[1] He notes that the paper, prepared largely independently of the
manufacturer (whatever that means), examines data on miscarriage rates in
two large trials of the bivalent HPV vaccine (Cervarix, GSK).
At the start of the last paragraph of the summary he writes, “the
authors conclude that overall, there was no evidence for any association
between the bivalent HPV vaccine and miscarriage.” But Jim Glare then
noted, as did Jo Waller and her colleague, that miscarriage rates were
higher in the HPV vaccine arm (containing the new AS04 adjuvant) than in
the control arm, “in pregnancies that began within three ….” …. indeed
suggesting (albeit according to the entirely arbitrary standard of
scientific practice, not statistically significantly) that miscarriage was
more common in the HPV vaccine group. However, what Wacholder et al did
write was,
“A small increase seen in risk of miscarriage in the subgroup of
pregnancies conceived within three months of vaccination is compatible
with chance, but does raise concern for a vaccine that is likely to be
administered to millions of women of reproductive age.” [2]
I don’t think this study lets Cervarix out of the scientific woods
and I don’t think Jo Waller and her colleague should be entirely reassured
about the vaccine’s statistical safety.
[1] Bivalent HPV vaccine does not significantly increase risk of
miscarriage. Jim Glare, NELM.
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---March/03/Bivalent-HPV-
vaccine-does-not-significantly-increase-risk-of-miscarriage/
[2] Risk of miscarriage with bivalent vaccine against human
papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised
controlled trials. Sholom Wacholder et al, BMJ 2010;340:c712
Competing interests:
None declared
Competing interests: No competing interests