Content uploaded by Elisabete Weiderpass
All content in this area was uploaded by Elisabete Weiderpass on Jul 22, 2015
Content may be subject to copyright.
Perineal use of talc and risk of ovarian cancer
S E Hankinson,
The Cancer Registry of
Norway, Institute of population-
based Cancer Research, Oslo,
Department of Medicine,
Brigham and Women’s Hospital
and Harvard Medical School,
Boston, MA, USA;
of Social and Preventive
Medicine, University of
Montreal, Montreal, Canada;
Department of Medical
Epidemiology and Biostatistics,
Karolinska Institutet, Stockholm,
Folkha¨lsan, Helsinki, Finland
E Weiderpass, The Cancer
Registry of Norway, 0310 Oslo,
Accepted 15 October 2007
Ovarian cancer is one of the most common gynaecological
neoplasms, especially in industrialised countries. The
aetiology of the disease is not well understood, except
that inherited mutations in the breast cancer genes BRCA-
1 and BRCA-2 account for up to 10% of all cases,
child-bearing, oral contraceptive use and breast-feeding
reduce the risk.
Some environmental exposures, notably
talc and asbestos, have been suspected as ovarian
Talc refers to both mineral talc and industrial
products that contain mineral talc. Mineral talc
occurs naturally in many regions of the world and
is valued for its softness, platyness, and ability to
absorb organic matter. Mineral talc occurs natu-
rally in a platy (flat) form, but may also occur as
asbestiform fibres, which describes its physical
form and does not imply the presence of asbestos.
The purer forms (approximately 90% mineral talc)
are used for cosmetic and hygiene products
including baby powders and feminine hygiene
products. Perineal use of cosmetic talc is a common
practice in the United Kingdom, North America,
Australia and some other countries. To our knowl-
edge accurate estimates of prevalence of use of
cosmetic talc are not available. However, the use
for female hygiene of body powders, baby pow-
ders, talcum powders and deodorising powder,
most of which contain cosmetic talc in varying
amounts, has been reported to be as high as 50% in
From pathological studies it is known that
particles and fibres that enter the body can migrate
to distant organs. For instance, asbestos fibres have
been found in ovaries from women exposed to
Analogously, following perineal appli-
cation, talc particles can migrate from the vagina to
the peritoneal cavity and ovaries.
A majority of
women experience retrograde menstruation
suggests a mechanism by which talc particles can
travel through the female reproductive tract to the
ovaries. Furthermore, epidemiological studies have
shown decreased risks of ovarian cancer after tubal
ligation and/or hysterectomy, suggesting that
removing a pathway by which carcinogenic sub-
stances can reach the ovaries reduces the risk.
The association between talc use in the perineal
region and ovarian cancer was investigated in one
and 20 case-control studies.
the cohort study, arguably the strongest study
because of its partly prospective ascertainment of
exposure, there was no association between
cosmetic talc use and risk of all subtypes of ovarian
cancer combined. The various case-control studies
provided indications of either a significant excess
risk (10 studies) or non-significant excess risk or
null (10 studies), with odds ratios (ORs) ranging
from 1.0 to 3.9. None of the studies reported
relative risks below 1.0. The population-based case-
11 15–17 20–26 28–30
included studies with
112–824 ovarian cancer cases, and had odds ratios
ranging from 1.1 to 3.9 (fig 1). The hospital-based
case control studies
12–14 18 19 27
included studies with
77–462 cases, and reported odds ratios between 1.0
and 2.5. Pooled odds ratios were calculated by fixed
effects model. As shown in figure 1 pooled ORs
were 1.40, 1.12 and 1.35 for population-based,
hospital-based and all case control studies com-
bined, respectively. Some studies
13 14 22 23 26 28
to assess exposure-response associations, in terms
of frequency of use or length of use in years but
found no clear trend.
Methodological factors such as recall bias should
always be considered in case-control studies. It
could have been a problem had there been wide-
spread publicity about the possible association
between use of body powder and cancer. The
International Agency for Research on Cancer
(IARC) working group considers that there has
not been widespread public concern about this
issue and therefore considers it unlikely that such a
bias could explain the consistent findings. Another
source of recall bias could result from the fact that
women with the cancer tend to remember or over-
report their use of body powder. The influence of
this type of recall bias cannot be ruled out.
Eight of the population-based case-control stu-
11 16 22–24 26 28 29
were identified, by the IARC
working group as being most informative in terms
of size of the studies, whether the studies were
population-based, participation rates and adjust-
ments of confounding variables. The selected studies
included at least 188 cases and had participation
rates ranging from 60% to 75%. Among these eight
studies, the prevalence of perineal use of talc-based
body powder among controls ranged from 16% to
52%. The relative risks of ovarian cancer among
body powder users were homogeneous across this
set of eight studies, each of which indicated a 30–
60% increase in risk. Among the other 12 case-
control studies, most also reported relative risks of
this magnitude or higher.
Information on talc use in infancy is generally
insufficient in the case-control studies. However, in
one study the exposure to baby powder was
reported by 42.2% of the cases and 40.5% of the
In several of the other studies patients
were asked about age at first use of perineal talc, as
an indicator for use in infancy or other periods of life.
Only four case-control studies
16 23 29 30
provided results by histological type.
In four of these studies, in particular the cohort
study, there were hints of higher risks of serous
tumours related to talc exposure.
358 J Epidemiol Community Health 2008;62:358–360. doi:10.1136/jech.2006.047894
Before 1976, talc was to some extent contaminated with
asbestos, so that the early studies relating talc to ovarian cancer
may have been confounded by the asbestos.
association between talc exposure and ovarian cancer is as
strong in recent studies,
as in earlier ones, diminishing the
likelihood that all these results are influenced by contamination
of talc by asbestos.
To summarise the evidence in favour of an association, a very
large number of studies have found that women who used talc
experienced excess risks of ovarian cancer; some results were
statistically significant and some were not. There was some
indication in the cohort study of an increase in serous tumours.
The evidence of talc migrating to the ovaries lends credibility to
such a possible association. The main epidemiological evidence
against the association is the absence of clear exposure-response
associations in most studies, as well as the absence of an overall
excess risk in the cohort study.
On balance, the epidemiological evidence suggests that use of
cosmetic talc in the perineal area may be associated with
ovarian cancer risk. The mechanism of carcinogenicity may be
related to inflammation.
The carcinogenicity of non-asbestiform talc was assessed by a
monograph working group at IARC in 2006.
biases and possible confounding factors, the IARC working
group concluded that the epidemiological studies provided
limited evidence for the carcinogenicity of perineal use of talc-
based body powder, and classified this use as possibly
carcinogenic to human beings (that is, group 2B).
PROPOSAL: TO RESEARCH COMMUNITY
The current body of experimental and epidemiological evidence
is insufficient to establish a causal association between perineal
use of talc and ovarian cancer risk. Experimental research is
needed to better characterise deposition, retention and clearance
of talc to evaluate the ovarian carcinogenicity of talc.
The majority of the epidemiological studies carried out so far
have been among American women. It would be instructive to
seek evidence in other countries where perineal use of talc has
While there has been some efforts to measure the degree of
use, these have mainly been measured simply as the reported
years of use. It is possible that the ostensible lack of exposure
response trends is the result of crudeness of the exposure metric
used. Therefore, it is important that future studies, irrespective
of study design, devote some effort to better assessment of
exposure. The use of body powders should be assessed both in
terms of calendar time and age of the subject. Subjects should be
asked about lifetime use, including age at initial use (infancy,
childhood, teenager years, adulthood), age at which they
stopped using such powders, gaps in the lifetime period of use
Figure 1 Results from case-control studies contributing data on perineal talc use and ovarian cancer. Results are presented as odds ratios (ORs) and
their corresponding confidence intervals (95% CIs) and represented by squares and lines, respectively. Results are separated in 14 population-based
and six hospital-based case-control studies. Pooled ORs for all population-based studies combined and all hospital-based studies combined are given.
OR pooling by fixed effect models (Mantel-Haenszel method).
J Epidemiol Community Health 2008;62:358–360. doi:10.1136/jech.2006.047894 359
and frequency and nature of use (daily, during certain seasons of
the year, only while menstruating). Another important ques-
tion is whether the use of body powder was before or after tubal
ligation or hysterectomy.
Individuals’ answers to questions about use of brand names
over time may be unreliable, and therefore, in future studies,
investigators should try to ascertain, either from government or
industry sources, the composition of the powders used in
different time periods by different brand names and, in
particular, to ascertain whether the exposure may have included
some contamination by asbestos and also whether the exposure
was to talc or a non-talc product. Statistical analyses should
attempt to assess risk separately for the categories of powders:
talc containing asbestos, talc not containing asbestos, non-talc
product. Further, exposure metrics should take into account the
age, duration and intensity of exposure. As well as analyses for
all ovarian tumours combined, there should, if possible, be
analyses by histological subtype and by invasiveness of the
While it would not be reasonable to envisage establishing a
costly long-term prospective cohort study just to study this
association, any long-term cohort study that is being set up to
study cancer among women should collect information about
talc use if the study is being conducted in a country where such
use has been widespread.
In summary, future studies should focus on seeking evidence
in talc-exposed female populations worldwide, collecting reli-
able information on age at initial use of body powder, exposure
assessments and dose response associations.
Acknowledgements: The work reported in this paper was initiated while SH, JS and
EW were part of an IARC Monographs Working Group of the International Agency for
Research on Cancer, Lyon, France.
Funding: This study was financed by the Cancer Registry of Norway.
Competing interests: None.
1. Lux MP, Fasching PA, Beckmann MW. Hereditary breast and ovarian cancer: review
and future perspectives. J Mol Med 2006;84:16–28.
2. Persson I. Estrogens in the causation of breast, endometrial and ovarian cancers—
evidence and hypotheses from epidemiological findings. J Steroid Biochem Mol Biol
3. International Agency for Research on Cancer. IARC monographs on the
evaluation of carcinogenic risks to human, Vol 93, Carbon black, titanium dioxide, and
non-asbestiform talc. Geneva: WHO (in press).
4. Heller DS, Gordon RE, Westhoff C, et al. Asbestos exposure and ovarian fiber
burden. Am J Ind Med 1996;29:435–9.
5. Langseth H, Johansen BV, Nesland JM, et al. Asbestos fibers in ovarian tissue from
Norwegian pulp and paper workers. Int J Gynecol Cancer 2007;17:44–9.
6. Venter PF. Ovarian epithelial cancer and chemical carcinogenesis. Gynecol Oncol
7. Olive DL, Schwartz LB. Endometriosis. N Engl J Med 1993;328:1759–69.
8. Rosenblatt KA, Thomas DB. Reduced risk of ovarian cancer in women with a tubal
ligation or hysterectomy. the World Health Organization Collaborative Study of
Neoplasia and Steroid Contraceptives. Cancer Epidemiol Biomarkers Prev
9. Tortolero-Luna G, Mitchell MF. The epidemiology of ovarian cancer. J Cell Biochem
10. Gertig DM, Hunter DJ, Cramer DW, et al. Prospective study of talc use and ovarian
cancer. J Natl Cancer Inst 2000;92:249–52.
11. Cramer DW, Welch WR, Scully RE, et al. Ovarian cancer and talc: a case-control
study. Cancer 1982;50:372–6.
12. Hartge P, Hoover R, Lesher LP, et al. Talc and ovarian cancer. JAMA
13. Whittemore AS, Wu ML, Paffenbarger RS Jr, et al. Personal and environmental
characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder,
tobacco, alcohol, and coffee. Am J Epidemiol 1988;128:1228–40.
14. Booth M, Beral V, Smith P. Risk factors for ovarian cancer: a case-control study.
Br J Cancer 1989;60:592–8.
15. Harlow BL, Weiss NS. A case-control study of borderline ovarian tumors: the
influence of perineal exposure to talc. Am J Epidemiol 1989;130:390–4.
16. Harlow BL, Cramer DW, Bell DA, et al. Perineal exposure to talc and ovarian cancer
risk. Obstet Gynecol 1992;80:19–26.
17. Chen Y, Wu PC, Lang JH, et al. Risk factors for epithelial ovarian cancer in Beijing,
China. Int J Epidemiol 1992;21:23–9.
18. Rosenblatt KA, Szklo M, Rosenshein NB. Mineral fiber exposure and the
development of ovarian cancer. Gynecol Oncol 1992;45:20–5.
19. Tzonou A, Polychronopoulou A, Hsieh CC, et al. Hair dyes, analgesics, tranquilizers
and perineal talc application as risk factors for ovarian cancer. Int J Cancer
20. Cramer DW, Xu H. Epidemiologic evidence for uterine growth factors in the
pathogenesis of ovarian cancer. Ann Epidemiol 1995;5:310–4.
21. Purdie D, Green A, Bain C, et al. Reproductive and other factors and risk of epithelial
ovarian cancer: an Australian case-control study. Survey of Women’s Health Study
Group. Int J Cancer 1995;62:678–84.
22. Chang S, Risch HA. Perineal talc exposure and risk of ovarian carcinoma. Cancer
23. Cook LS, Kamb ML, Weiss NS. Perineal powder exposure and the risk of ovarian
cancer. Am J Epidemiol 1997;145:459–65.
24. Green A, Purdie D, Bain C, et al. Tubal sterilisation, hysterectomy and decreased risk
of ovarian cancer. Survey of Women’s Health Study Group. Int J Cancer
25. Godard B, Foulkes WD, Provencher D, et al. Risk factors for familial and sporadic
ovarian cancer among French Canadians: a case-control study. Am J Obstet Gynecol
26. Cramer DW. Perineal talc exposure and subsequent epithelial ovarian cancer: a
case-control study. Obstet Gynecol 1999;94:160–1.
27. Wong C, Hempling RE, Piver MS, et al. Perineal talc exposure and subsequent
epithelial ovarian cancer: a case-control study. Obstet Gynecol 1999;93:372–6.
28. Ness RB, Grisso JA, Cottreau C, et al. Factors related to inflammation of the ovarian
epithelium and risk of ovarian cancer. Epidemiology 2000;11:111–7.
29. Mills PK, Riordan DG, Cress RD, et al. Perineal talc exposure and epithelial ovarian
cancer risk in the Central Valley of California. Int J Cancer 2004;112:458–64.
30. Jordan SJ, Green AC, Whiteman DC, et al. Risk factors for benign serous and
mucinous epithelial ovarian tumors. Obstet Gynecol 2007;109:647–54.
31. Harlow BL, Hartge PA. A review of perineal talc exposure and risk of ovarian cancer.
Regul Toxicol Pharmacol 1995;21:254–60.
32. Ness RB, Cottreau C. Possible role of ovarian epithelial inflammation in ovarian
cancer. J Natl Cancer Inst 1999;91:1459–67.
33. International Agency for Research on Cancer. Preamble to the IARC
monographs on the evaluation of carcinogenic risks to humans. 93. Lyon: IARC
34. Baan R, Straif K, Grosse Y, et al. Carcinogenicity of carbon black, titanium dioxide,
and talc. Lancet Oncol 2006;7:295–6.
What this study adds
c Epidemiological evidence suggests that use of cosmetic talc in
the perineal area may be associated with ovarian cancer risk.
The IARC has classified this use of talc as possibly
carcinogenic to human beings (group 2B).
c The mechanism of carcinogenicity may be related to
inflammation. This paper focus on the high degree of
consistency in the studies accomplished so far, and what
should be the focus in future studies.
360 J Epidemiol Community Health 2008;62:358–360. doi:10.1136/jech.2006.047894