world cancer report - iarc

Infection
Subclinical
Mutagenic factors
and estrogen
derivatives
Upregulation of viral
gene activity
and amplification
of viral DNA
Viral DNA
persistence
Low grade squamous
intraepithelial
lesion
Fig. 2.43 Proposed pathogenetic mechanism by which human papillomavirus infection causes cervical
cancer. Adapted from H zur Hausen, Virology 184, 9-13 (1991).
Human herpes virus 8
Human herpesvirus 8 (HHV-8) infection
appears to be common in Africa and in
some Mediterranean countries but rare
elsewhere. HHV-8 DNA has been detected
in over 90% of Kaposi sarcomas and rarely
in control patients. Seropositivity rates
are also higher in cases than controls,
with relative risks over 10 in most studies.
Accordingly, the evidence linking HHV-8
to Kaposi sarcoma is strong [9]. Certain
lymphoproliferative diseases such as primary
effusion lymphoma and Castleman
disease have also been linked to HHV-8,
but the evidence is very limited [7].
Helicobacter pylori
Infection with Helicobacter pylori is one of
the most common bacterial infections
worldwide. In developing countries, the
prevalence of H. pylori among adults
ranges from 80 to 90% whilst in developed
areas it is around 50%. H. pylori is the
main cause of gastritis and peptic ulcer;
infection may be lifelong if not treated
with antibiotics [12]. The relationship
between gastric cancer and H. pylori has
been difficult to determine due to the very
high prevalence of H. pylori in most populations
where the cancer is endemic and
the very low bacterial load usually found in
gastric cancer patients. It is clear that H.
58 The causes of cancer
Modification of
host cell genes
modulating viral
gene expression
High grade squamous
intraepithelial
lesion
Genomic instability
induced by increased
viral gene expression
Integration and/ or
viral intragenomic
modificatons
Invasive cancer
Mutations of
additional host
cell genes affecting
differentiation
and angiogenesis
Enhanced invasive
growth, metastases
pylori plays a role in gastric cancer, but
other cofactors (e.g. diet) are also contributory
(Stomach cancer, p194).
Parasites
Two liver flukes, Opisthorchis viverrini and
Clonorchis sinenesis, have been associated
with cholangiocarcinoma in parts of Asia
(Liver cancer, p203). Infection by these
flukes is acquired by eating raw or undercooked
freshwater fish containing the
infective stage of the fluke; the fluke
matures and produces eggs in the small
intrahepatic ducts [4]. The evidence for
cancer causation by O. viverrini, a parasite
mainly prevalent in Thailand, is stronger
than for C. sinensis. The incidence of
cholangiocarcinoma in areas where these
liver flukes are non-endemic is very low.
Schistosomes are trematode worms. The
cercarial stage infects humans by skin penetration.
The worms mature and lay eggs in
the bladder or intestine of the host, provoking
symptoms of a disease known as
bilharzia. Schistosoma haematobium infection
is prevalent in Africa and the Middle
East and has been identified as a cause of
bladder cancer. Schistosoma japonicum
infection is prevalent in Japan and China
and has been associated with cancers of
the liver, stomach and colorectum, but the
evidence is weak and inconsistent [4].
Fig. 2.44 Processing samples for HPV testing as
part of a study of HPV prevalence in Thailand.
Fig. 2.45 The Helicobacter pylori bacterium structure
as revealed by scanning electron microscopy.
Fig. 2.46 Chronic infection of the bladder with
Schistosoma haematobium causes an inflammatory
reaction with dense eosinophilic infiltrates
which may cause the development of a squamous
cell carcinoma.
Mechanisms of carcinogenicity
Two main pathogenic mechanisms have
been invoked for infectious agents associated
with cancer [13]. The first is a direct
effect, when agents act directly on the
cells which are ultimately transformed.
HPV-induced cancer of the cervix is the
best understood example of a “direct”
effect in humans. The E5 oncoprotein
expressed by high-risk HPV types may play
a role in the early growth stimulation of