Annals of Oncology Advance Access originally published online on January 5, 2007
Annals of Oncology 2007 18(2):401-403; doi:10.1093/annonc/mdl423
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© 2007 European Society for Medical Oncology
letters to the editor |
Reply to the article ‘Hepatitis C virus (HCV) infection and MALT-type ocular adnexal lymphoma (OAL)’ by P. Arnaud, M.-C. Escande, M. Lecuit et al. (Ann Oncol doi:10.1093/annonc/mdl369)
According to the interesting letter from Arnaud et al. [1], the prevalence of hepatitis C virus (HCV) infection in ocular adnexal lymphoma (OAL) patients diagnosed at the Institut Curie is 2%, which is significantly lower compared with the 13% observed in our series [2]. Intriguingly, the single French patient with OAL and HCV infection displayed a disseminated lymphoma and was the sole patient who died of lymphoma progression, which is in line with the negative prognostic impact of HCV infection observed in our OAL patients [2] and in other lymphoma categories, even in French series [3].
The role of HCV in lymphomagenesis is indicated by the higher prevalence of HCV seropositivity in patients with B-cell lymphomas (
15%), with respect to the general population (1.5%) and patients with other hematological malignancies (2.9%) [4]. Variations in the HCV–lymphoma association among different countries (i.e. 20% in Italy, 14% in Japan, 11% in United States, and 6.4% in other European countries) [4] and different regions within the same country [5], however, have been frequently reported. The discrepancies in the HCV prevalence between the French [1] and Italian [2] OAL series should be considered as one more of these well-known variations. These figures could be simply explained by the fact that HCV appears to be associated with B-cell lymphomas mainly in areas where the infection is highly prevalent in the general population [1.15% in France [6] versus 3% in Italy; 4% in Southern Italy (A. Mele, personal communication; Istituto Superiore di Sanità, Rome). Some epidemiological studies carried out in countries with a low HCV prevalence, such as Sweden (
0.5%), have, however, confirmed a significantly increased risk for non-Hodgkin's lymphoma (NHL) in HCV-positive patients [7]. In this scenario, other methodological and selection factors, such as the inclusion of different lymphoma categories and HCV genotypes, which could have variable degrees of lymphotropism and oncogenic potential [8–10], may contribute to the marked variability in worldwide literature.
The epidemiological picture of HCV infection in the general population is largely unknown, but some cross-sectional studies indicate that HCV epidemiology is changing in some areas. In Italy, for instance, an increase of genotypes 1a and 3a and a marked reduction of genotype 2 have been reported [11]. Moreover, there is a trend to a lower incidence of HCV infection in Italian individuals <50 years (A. Mele, personal communication), which may result in a lower incidence of HCV-related NHL in the next decades considering that an exposition to HCV infection >15 years is required for lymphoma development [7, 8]. These changes in HCV epidemiology and variability in prevalence indicate that other factors (environmental, genetic and/or ethnic) may contribute, in combination or not with HCV, to trigger a B-cell expansion into a lymphoma. In this context, emerging infectious agents able to induce persistent infections could play a relevant role in the pathogenesis of marginal-zone lymphomas. A potential paradigm could be offered by the reported strong association between OAL and Chlamydia psittaci infection [12], which lead to a new active antibiotic therapy for these malignancies [13]. Also in this association, a geographical variability is evident [14], and it is worthwhile to underline that the prevalence of the C. psittaci infection in Italian patients with OAL varied over time, with a higher prevalence among OAL cases diagnosed in the 1990s and a lower prevalence after the year 2000 (Figure 1). On these grounds, we believe that the real prevalence of a distinct lymphoma–infection association should be defined taking into account not only the geographical area but also the period of time in which the malignancies were diagnosed. This is of great relevance, if we consider that antimicrobial therapy could play a central role in the management of marginal-zone lymphomas. In this respect, we agree with Arnaud et al. [1] that the efficacy of antiviral therapy in HCV-positive patients with OAL remains to be thoroughly investigated considering that, at our best knowledge, a single case of HCV-positive OAL successfully treated with interferon and ribavirin has been reported so far [15].
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1 Medical Oncology Unit, San Raffaele Scientific Institute, Milan
2 Immunovirology and Biotherapy Unit, Department of Pre-Clinical and Epidemiological Research, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano
3 U.O.C. di Ematologia e Trapianto di Cellule Staminali, Centro di Riferimento Oncologico di Basilicata, Ospedale Oncologico Regionale, Rionero in Vulture, Potenza
4 Pathology Unit, San Raffaele Scientific Institute, Milan, Italy
* E-mail: andres.ferreri{at}hsr.it
References
1. Ann Oncol Arnaud P, Escande M-C, Lecuit M, et al. Hepatitis C virus infection and MALT-type ocular adnexal lymphoma. doi:10.1093/annonc/mdl369.
2. Ferreri AJ, Viale E, Guidoboni M, et al. (2006) Clinical implications of hepatitis C virus infection in MALT-type lymphoma of the ocular adnexa. Ann Oncol 17:5769–772.
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12. Ferreri AJ, Guidoboni M, Ponzoni M, et al. (2004) Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 96:8586–594.
13. Ferreri AJM, Ponzoni M, Guidoboni M, et al. (2006) Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst 98:1375–1382.
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