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Participate
in vaccination programmes against Hepatitis B Virus infection
About 18% of human cancers worldwide
are currently attributable
to persistent infections with viruses, bacteria or parasites.
In the
European Union this fraction is about 10%, and it is chiefly
accounted by four cancer sites or types, namely cancer of
the
cervix uteri, liver, stomach and some haemo-lymphopoietic
tumours. Knowledge about the role of infectious agents in
the aeti-
ology of several cancer types has rapidly expanded in the
last 30
years, after major improvements were made in the detection
of
markers of chronic infection. Contrary to former beliefs,
antibacterial
and antiviral treatments, as well as vaccination programs,
represent an important tool against cancer.
The
four major cancer sites or types that have been linked to
infectious agents figure
7 will
be discussed below, with special reference to current opportunities
for prevention in the European Union, EU, countries.
Every
year approximately
25.000
women in the European Union develop cervical cancer. A dozen
types of human
papillomavirus, HPV, have been identified
in 99% of biopsy specimens from cervical cancer worldwide,
and in Europe HPV 16 has been reported in 56% of over 3.000
cervical cancer specimens. Five HPV types (HPV 16, 18, 31,
33, 45) account for >85% of European cervical cancer specimens.
In control women, the prevalence of the indicated HPV types
is several dozen-fold lower. There is no effective medical
treatment against HPV; however, very sensitive and specific
tests for the detection of HPV DNA in cervical cells have
become available. There is sufficient evidence for recommending
HPV testing among women who show borderline or low-grade cytological
abnormalities. Additionally, HPV testing improves the follow-up
of women who have been treated for cervical intra-epithelial
lesions, CIN, and, pending results of
ongoing trials, may offer a more sensitive alternative to
cytology in primary cervical cancer screening.
A
prophylactic vaccine, based on late (L) 1 HPV 16 proteins,
has been shown to be safe, highly immunogenic and efficacious
in preventing persistent HPV infections in a trial of 1523
HPV 16- negative young women in the USA. A multivalent vaccine
against the most common oncogenic HPV types may thus ultimately
represent the most effective way to prevent cervical cancer
worldwide, alone or in combination with screening. Vaccination
would benefit women who do not attend screening programs in
the EU and, if combined with current screening programs, it
would allow substantial savings (i.e., less frequent screening
tests, fewer treatments, etc.).
Every
year approximately
30.000
new cases of liver cancer are recorded in the European Union
figure
4.
Upward trends in incidence and mortality rates have been seen
in the last two decades, in men in France, Germany and Italy.
Chronic infection with hepatitis B virus, HBV, and
hepatitis C virus, HCV, accounts for
the majority of liver cancer cases in Europe. In a large case-series
of liver cancer from six European Liver Centres only 29% of
503 liver cancer patients had no marker of either HBV or HCV
infection.
An
effective vaccine against HBV has been available for 20 years
now. Several countries in the European Union (e.g., Denmark,
Finland, Ireland, The Netherlands, Sweden and the United Kingdom
) do not perform routine vaccination against HBV in children,
on account of the low prevalence of HBV infection in the general
population (http://www.who.int/),
whereas other countries (e.g. Belgium, France, Germany) report
coverage below 50%. There is scope for reconsidering national
policies regarding universal vaccination against HBV since
selective vaccination of high-risk groups rarely works, and
travelling and migration facilitate the mixing of high- and
low-risk populations. Although infection with HBV in young
adulthood (typically through sexual intercourse or contaminated
needles) carries a much lower risk of chronic hepatitis and
liver cancer than infection at birth or during childhood,
it frequently induces acute hepatitis.
HCV
represents an increasing problem in several areas of the European
Union (especially Italy, Greece and Spain) and in some population
groups, notably intravenous drug users. A vaccine is not yet
available, and the effectiveness of treating all HCVRNA positive
individuals with pegylated interferon-2a with or without ribavirin
is still under evaluation. Hence, the prevention of HCV infection
relies for the moment on a strict control of blood and blood
derivatives and avoidance of use of non-disposable needles
in medical and non-medical procedures (e.g. acupuncture, tattooing,
etc).
Helicobacter
pylori, Hp, is associated with an approximatley 6-fold increased
risk of non-cardia gastric cancer. Out of approximatley 78.000
new cases of gastric cancer every year in the EU, some 65%
may be attributable to Hp (assuming an Hp prevalence of about
35% in the general population). The current therapy of Hp
infection, based on the use of proton-pump inhibitors and
antibiotics, is efficacious but poor patient compliance, antibiotic
resistance and recurrence of infection complicate the issue.
Furthermore, although treatment of Hp infection can induce
regression of gastric lymphoma, it has not yet been shown
to reduce gastric cancer risk. Various approaches have been
followed in the development of vaccines against Hp, based
on the use of selected Hp antigens, notably urease, the vacuolating
cytotoxin, VacA, the cytotoxin-associated antigen, CagA, and
the neutrophil-activating protein, NAP. Unfortunately, the
natural history of Hp infection and the characteristics of
an effective anti-Hp immune response are still poorly understood.
Pharmaceutical companies seem to be reluctant to invest in
the long and uncertain process of developing a vaccine against
Hp, an infection perceived as declining and amenable to medical
treatment.
The
fourth group of cancers where infectious agents are known
or suspected to play a major role is haemo-lymphopoietic tumours
( i.e. non-Hodgkin’s lymphomas, NHL; Hodgkin's disease,
HD; and leukaemias]— a total approximately 104.000 new
cases per year in the EU). Certain viruses (i.e. Epstein Barr
virus, EBV; human immunodeficiency virus, HIV, human-T-cell
leukaemia/lymphoma virus 1, Herpes simplex type 8 and HCV)
and Hp account for an illdefined proportion of NHL and HD.
Childhood leukaemias may also be linked to one or more not
yet identified infectious agents. As for Hp and gastric lymphomas,
treatment of HCV has led to the regression of some extra-nodal
NHL. Highly active antiretroviral therapy (HAART) has had
a favourable impact on the occurrence of Kaposi’s sarcoma,
but not as yet of NHL, in HIV-infected patients. Recognising
and treating infections linked to haemolymphopoietic tumours
is a priority in the EU, on account of the steady increase
in the number of cases and high-risk individuals (e.g. iatrogenically
immuno-suppressed and HIVpositive subjects).
In conclusion, infectious agents account
for a substantial fraction
of cancers in the European Union. For the moment, priorities
are the expansion of immunisation programs against HBV and
the
inclusion of HPV testing in cervical cancer screening programs.
Vaccines against cancer-causing infectious agents are, however,
one of the most promising ways to prevent or even cure some
important tumours. Because of the enormous cost of vaccine
development, public–private partnerships (e.g. the Global
Alliance
for Vaccines and Immunisation, GAVI for developing countries)
should be actively pursued in the EU, especially with
respect to the development of vaccines against HCV and Hp.
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