world cancer report - iarc

CHRONIC INFECTIONS
SUMMARY
> Infectious agents are one of the main
causes of cancer, accounting for 18%
of cases worldwide, the majority
occurring in developing countries.
> The most frequently affected organ
sites are liver (hepatitis B and C, liver
flukes), cervix uteri (human papillomaviruses),
lymphoid tissues (Epstein-
Barr virus), stomach (Helicobacter
pylori) and the urinary system
(Schistosoma haematobium).
> The mechanism of carcinogenicity by
infectious agents may be direct, e.g.
mediated by oncogenic proteins produced
by the agent (e.g. human papillomavirus)
or indirect, through causating
of chronic inflammation with tisssue
necrosis and regeneration.
>Strategies for prevention include vaccination
(hepatitis B virus), early detection
(cervical cancer) and eradication of the
infectious agent (Helicobacter pylori).
Infectious agents can cause cancer
That cancer can be caused by infectious
agents has been known for more than 100
years. Early in the last century, Peyton
Rous demonstrated that sarcomas in
chickens were caused by an infectious
agent, later identified as a virus [1].
However, the identification of infectious
agents linked to human cancer has been
slow, in part because of difficulties in
detecting indicators of exposure. Progress
has accelerated since the 1980s when
advances in molecular biology made possible
the detection of a very small quantity
of infectious agent in biological specimens.
A further difficulty is the fact that
relevant infectious agents tend to persist
silently for many years, before causing
cancer in only a small proportion of chronically
infected individuals.
56 The causes of cancer
Fig. 2.41 Electron microscopy of hepatitis B virus
particles.
Today, experimental and epidemiological
evidence indicates that a variety of infectious
agents constitute one of the main
causes of cancer worldwide [2]. Viruses
are the principal ones, with at least eight
different viruses associated with particular
tumour types, with varying degrees of
certainty. Other infectious agents involved
in carcinogenesis are four parasites and
one bacterium [3-7] (Table 2.18).
Hepatitis B and C viruses
Worldwide, about 2,000 million people
have serological evidence of current or
past hepatitis B virus (HBV) infection and
about 350 million of them are chronic carriers
of the virus. Infection can be transmitted
from mother to child (vertical
transmission), child to child (horizontal
transmission), through sexual transmission
and by contact with infected blood.
Horizontal transmission is responsible for
the majority of infections in the world,
although the exact mechanisms of child to
child transmission remain unknown. Close
contact of young children is the primary
risk factor and exposure to skin lesions,
sharing food and utensils, tattooing and
scarification procedures, and transmission
by insects are some of the postulated
mechanisms. The use of contaminated
needles for medically-related injections
may have played a role, probably via therapeutic
injections rather than vaccination.
Several case-control and cohort studies
have clearly and consistently demonstrat-
Fig. 2.42 The human immunodeficiency virus
finds refuge in T-lymphocytes, as shown by the
electron micrograph.
ed that chronic carriers of HBV, identified
by the presence of relevant antibodies in
the sera, have around a 20 times higher
risk of developing liver cancer than noncarriers
[3]. It has been estimated that
60% of cases of primary liver cancer
worldwide and 67% of cases in developing
countries can be attributed to chronic persistent
infection with HBV [2]. In many situations,
exposure to aflatoxins is a related
risk factor (Food contaminants, p43).
Hepatitis C virus (HCV) is the major cause
of parenterally transmitted hepatitis
worldwide. Strong associations with relative
risks around 20 have been reported in
several case-control studies. About 25% of
cases of liver cancer in the world are
attributable to HCV [3].
Human papillomavirus
Over 100 human papillomavirus (HPV)
types have been identified and about 30
are known to infect the genital tract.
Genital HPV types are subdivided into
low-risk (e.g. 6 and 11) and high-risk or
oncogenic types (e.g. 16, 18, 31 and 45)
[5]. Dozens of molecular epidemiological
studies [5, 8, 9] have consistently
shown relative risks for invasive cervical
cancer ranging from 20 to over 100. In
fact, HPV DNA is found in virtually all
invasive cervical cancers, indicating that
HPV is a necessary cause [10] (Cancers
of the female reproductive tract, p215).
Moreover, about 80% of anal cancers and
30% of cancers of the vulva, vagina, penis