New evidence underscores the need for change in how the medical community regards cancer, writes Ethan Troy-Barnes
Cancer may be initiated by a diversity of instigators, ranging from lifestyle factors such as diet, to other factors such as the exposure to toxic chemicals. However, only in recent years have we come to fully appreciate the importance of one set of carcinogens in particular: infectious agents.
The Lancet Oncology has just last week published a systematic review on the subject, collating data from across the world in order to determine the exact contribution of infectious microorganisms to the cancer burden as a whole.
Previous studies like this one have been carried out twice before, for 1990 and 2002. This study – which looks at the figures for 2008 – is really an updating of data from 2002, that is by now a decade out of date.
First of all, how does getting an infection lead to cancer? Well, in addition to causing conventional symptoms like a fever or an upset stomach, it has been observed that certain types of infection are also linked with malignant growth in the body.
In such cases, the infecting bug will usually trigger some sort of malignant change in the biology of the cells it comes into contact with. However, it often takes a long time for this alteration to take effect. In most cases, the cancerous growth usually won’t take place until years or even decades after the initial infection has passed.
This is only true of a tiny handful of infectious organisms. However, for the minority of pathogens is question, the effects can be quite potent. For example, human papilloma virus (HPV) often causes no symptoms in the individual, or may be associated with the relatively benign development of warts at the site of infection. However, in the case of certain subtypes of this virus (namely HPV 16 and 18), which are sexually transmitted and target the cervix of the female genital tract, there is a high incidence of cancer development.
It is important to realise that cancer being caused by an infectious agent does not mean it is contagious. Cancer cannot spread between individuals, only the infectious microbe can. Furthermore, getting infected by a carcinogenic pathogen will not always result in the development of cancer. Likewise, there are often other, non-infectious roots that can also lead to the cancer associated with a particular organism.
This brings us to relative risk (RR), population attributable fraction (PAF) and the results of the Lancet study. Relative risk describes how much more likely an exposure to a certain thing is to lead to a disease, compared with not being exposed. Note that the disease can still occur in the absence of exposure, but it’s just more likely to happen with exposure.
So, being infected by Helicobacter Pylori, a bacteria associated with a non-cardia gastric cancer (a type of stomach cancer), will not always lead to this cancer actually developing. The relative risk of getting cancer after being exposed to this agent is 5.9 – meaning that cancer is almost six times more likely to occur in an individual who gets this infection, compared to somebody who does not.
PAF is an extension of this concept, and describes the theoretical number of cases of a particular disease that would no longer exist were exposure to a particular agent eliminated. This study calculated the PAF of gastric cancer due to H. pylori to be about 75 per cent, i.e. if this agent were eradicated tomorrow, we would expect to see a decrease in the incidence of non-cardia gastric cancer of 75 per cent. This sort of figure highlights the significance of infectious agents as causes of certain types of cancer.
Overall, the Lancet study found that infectious agents accounted for approximately two million (16.1 per cent) of total 12.7 million new cancer cases occurring worldwide in 2008. These figures differed by developmental status – with infectious agents accounting for far more new cases of cancer (22.9 per cent) in less developed regions, than in more developed countries (7.4 per cent).
The four major culprits – accounting for over 90 per cent of these cases – were: H. pylori (32.5 per cent), HPV (30 per cent), and Hepatitis B and C viruses which cause liver cancer (29.5 per cent). Other notable pathogens included: Epstein-Barr virus, Human Herpes virus type B, Human T-cell Lymphotropic virus type 1 (HTLV-1), Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium.
In more developed countries, there was a shift in the figures in favour of H. pylori – with this agent accounting for a significant number (46.2 per cent) of cases, while the latter three microbes accounted for no cases in these regions. In addition, HTLV-1 accounted for almost three times the amount of new cancer cases in more developed countries.
The statistics collated by this report were roughly in line with previous studies. In fact, this latest report actually shows a decrease in the contribution of infectious agents compared to the 2002 report by a few per cent.
In terms of validity, the authors of this report claim that their research has a number of methodological strengths – providing the medical community with information that is highly accurate, as well as current. The infectious agents studied were only those for which there was the highest evidence of carcinogenicity, as determined by an expert review carried out by the International Agency for Research on Cancer. The authors also chose to calculate their PAF data from specific sources such as cancer case series, rather than more broad sources such as population surveys, which run the risk of being less representative of those at risk of developing cancer from infectious agents.
The main limitation of this study was that, being a worldwide report, there were some statistics that were not available for particular regions. As a result, data for certain counties had to be extrapolated from neighbouring regions in some cases.
However, in essence, what all of this amounts to is that the researchers erred on the side of caution – selecting only the data for which there was the most evidence and which was most accurate. As a result, the report does not take into account new and emerging types of cancer or carcinogenic pathogens, and paints a picture that may underestimate the importance of infectious agents in cancer.
Overall, this report underscores the importance of infectious agents in cancer. Many of these infections are easily treatable and detectable, e.g. in the case of H. pylori and HPV. Many infections are also readily preventable: the promotion of safe sexual and injection practices is proven to limit the spread of Hepatitis B virus. In addition, vaccination is available against Hepatitis B virus at birth, and for girls in the case of HPV and cervical cancer.
This reopens the debate as to whether or not these prevention measures should be extended to target other sets of people who are at risk. For example, it has been argued that the HPV vaccine be offered to males as well as females due to the virus’s emerging implication in oropharyngeal cancer. However, there are crucial knowledge deficits in these areas which must be filled before implementing such cancer prevention strategies.
In addition, this report’s findings must be taken in context. For instance, in 2004, a similar WHO study identified the PAF of nine lifestyle and environmental risk factors to be 35 per cent – around double that of infectious agents.
The multitude of other factors that contribute to the worldwide cancer burden as a whole must be taken into perspective when considering this data. Despite this, the authors petitions for a change in how we view cancer, arguing that in the future “although cancer is considered a major non-communicable disease, a sizable proportion of its causation is infectious and simple non-communicable disease paradigms will not be sufficient.”