There are Public Health programmes which could prevent cancers developing or increase the probability that a cancer may be cured. Early detection is an important factor in reducing the death rate from cancer, whether it is achieved by personal actions or through participation in organised public health programmes. Awareness of different visual body signs or symptoms that could easily be observed by anyone and that are possibly related to cancer is important. It is unequivocally established that cancer survival is better for early, localised disease than for the later stage, advanced forms of the disease. Thus, the earlier in the process that a cancer can be diagnosed and treated then the better this is for the patient. Potential symptoms of cancer should not be ignored, but should serve as a clear warning for the individual to consult his or her doctor for advice. The signs and symptoms described in Table 10 are not specific for cancer. When any one is present, the individual should see a doctor. Much effort has gone into cancer screening and the development of methods for finding cancers at an earlier stage in their development and increasing the prospects of a cure. It is possible to make recommendations based on the available evidence.
:: Participate in vaccination programmes against Hepatitis B Virus infectionAbout 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.