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Malignancy in systemic lupus erythematosus: what have we learned?

https://doi.org/10.1016/j.berh.2008.12.007Get rights and content

What have we learnt about cancer risk in systemic lupus erythematosus (SLE) over the past decade? One important lesson is that data do confirm a slightly increased risk in SLE for all cancers combined, compared to that in the general population. However, it is clear that this is largely driven by an increased risk for haematological malignancies, particularly non-Hodgkin's lymphoma (NHL), although Hodgkin's lymphoma may be increased as well. In addition, there is evidence for a moderately increased risk of lung cancer, and possibly for rarer cancer types such as hepatobiliary and vulvar/vaginal malignancies. Unfortunately, the most clinically relevant question – the mechanism underlying the association between cancer and SLE – remains largely unanswered. Key issues remaining relate to the links between cancer risk, SLE disease activity, and medication exposures. Much of the recent data suggest that disease-related factors may be at least as important as medication exposures for certain cancers, such as NHL. The independent effects of drug exposures versus disease activity in mediating cancer risk in SLE remain unknown. Work is in progress to further elucidate these important issues. Meanwhile, there is good evidence that cervical dysplasia is increased in women with SLE. This may be mediated by decreased clearance of the human papilloma virus, which some suggest is an innate characteristic of SLE patients. However, an increased risk of cervical dysplasia is also associated with immunosuppressive medication exposures, particularly cyclophosphamide. For these reasons, it is important that women with SLE follow established guidelines for cervical cancer screening.

Section snippets

Cancer risk in SLE relative to that in the general population

For some time there was significant debate as to whether persons with SLE did in fact have an increased risk of cancer compared to the general population. Of particular concern were haematological malignancies (particularly lymphoma) and lung cancer, two types of cancer that have been demonstrated to be elevated in other autoimmune rheumatic diseases such as rheumatoid arthritis (RA) [2].

In the past decade, several large studies have defined the magnitude of the cancer risk in SLE. A Swedish

More on lupus and haematological cancer risk

Evidence for an association between SLE and NHL was also suggested by Smedby et al in a population-based case–control study. Here, the frequency of autoimmune diseases among NHL patients from the general population was assessed and compared with matched population-based cancer-free controls [11]. Over 3000 NHL cases were studied, and of these, eight had a prior history of SLE, whereas only two of the matched cancer-free controls reported a history of SLE. The adjusted odds ratio (OR) for SLE

Characteristics of lung cancer risk in SLE

The multicentre international lupus cohort study demonstrated that SLE patients are at higher risk than the general population for lung cancer (SIR 1.37; 95% CI 1.05, 1.76). A review of the reported histology of the lung cancers from this study showed that the majority were adenocarcinoma, as is seen in the general population [22].

One study of lung cancers arising in various autoimmune rheumatic diseases (primarily systemic sclerosis, RA, and SLE) suggested that, on average, such malignancies

Is cancer risk in SLE driven by medication exposures?

Unfortunately, the most clinically relevant question, the mechanism underlying the association between cancer and SLE, remains largely unanswered. A potential link between cancer risk and drug exposures in SLE remains difficult to establish definitively because of the close association between lupus disease activity and use of immunosuppressives. Of note, it has been shown by several authors that the increased risk of lymphoma in SLE seems to be highest (relative to general population cancer

Haematological malignancies and inflammation

General support for the role of chronic autoimmunity and immune stimulation in haematological malignancy risk was suggested by several administrative database studies which found increased risk (compared to that in the general population) for patients with a diverse group of autoimmune conditions *[37], *[38]. One caveat of their methodology was the construction of study samples using hospitalization data, as it is well known that hospitalized people are more likely to be diagnosed with

Cervical dysplasia in women with SLE

The issue of cervical dysplasia remains of considerable importance in SLE. A group of SLE patients with normal cytology tests at baseline was followed to determine the incidence of cervical intraepithelial neoplasia (CIN) [45]. The 3-year incidence was 9.8%, significantly higher than figures for the general population. Interestingly, there were no new cases of CIN among SLE subjects exposed only to prednisone or azathioprine; in contrast, in subjects exposed to cyclophosphamide, the incidence

Summary

So far, we know that there is a slight increased risk in SLE for all cancers combined compared to that in the general population. However, this is largely driven by an increased risk for haematological malignancies, particularly NHL. Hodgkin's lymphoma may be increased as well. There is a moderately increased risk of lung cancer, and some evidence for increased risk of rarer cancer types, such as hepatobiliarly cancer and vulvar/vaginal malignancies.

There is also very good evidence that

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