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