Journal of the National Cancer Institute Advance Access originally published online on April 8, 2008
JNCI Journal of the National Cancer Institute 2008 100(8):600; doi:10.1093/jnci/djn087
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© The Author 2008. Published by Oxford University Press.
CORRESPONDENCE |
Re: Second Cancers Among 104760 Survivors of Cervical Cancer: Evaluation of Long-Term Risk
Affiliations of authors: Department of Urology, University of Florence, Florence, Italy (TC, RB); Sexually Transmitted Disease Center, Santa Maria Annunziata Hospital, Florence, Italy (SM)
Correspondence to: Tommaso Cai, MD, Department of Urology, University of Florence, Via dell’Antella, 58, 50011 Bagno a Ripoli, Florence, Italy (e-mail: ktommy{at}libero.it).
We read with interest the recent study by Chaturvedi et al. (1) concerning the risk of second cancers in a large number of survivors of cervical cancer. The authors of this well-designed and well-conducted study assessed the risk of second cancers that are known to be associated with human papillomavirus (HPV) infection and tobacco use in a cohort of 104760 women (1). During a follow-up period that spanned more than 40 years, they found 12496 incident cancers, 11720 of which were solid cancers. Among the patients with solid cancers, there were 949 urinary bladder cancer patients (8%), and 536 of these underwent radiotherapy and 109 did not. The authors reported an overall standardized incidence ratio (SIR) for urinary bladder cancer of 3.44 among all cervical cancer patients (1). Chaturvedi et al. (1) divided the secondary cancers into HPV and smoking-related cancers and considered bladder cancers to be smoking related.
We pose some questions based on these data to highlight the fact that HPV is a new challenge for urological research. First, what is the potential role of HPV in bladder cancer development? Among 949 bladder cancer cases, 109 had not undergone radiotherapy, suggesting that the impact of radiotherapy on secondary bladder cancer development is low, even if Chaturvedi et al. (1) reported SIRs of 3.51 and 1.93 for patients treated and not treated with radiotherapy, respectively. Furthermore, of the 109 patients affected by secondary bladder cancers who had not undergone radiotherapy, how many smoked? As previously suggested by others, the probable role of HPV in the development of bladder cancer should be considered (2–4). Chaturvedi et al. (1) highlighted the fact that the effects of radiation, HPV, and smoking may interact through common cellular pathways such as the p53 tumor suppressor pathway. In fact, the evidence that HPV interacts with p53 pathway, through E6 protein expression to produce an oncological disease after a long latency time is well established in the current literature (5). The authors also reported that among women who did not receive radiotherapy, statistically significantly elevated SIRs were observed in the period beyond 40 years of follow-up only for cancers of the urinary bladder (1). This raises the question as to whether the reported secondary bladder cancer cases are due to the fact that HPV infection causes cervical cancer and then, after a subsequent latency time, causes bladder cancer. Finally, we would like to highlight the fact that the difficulty in establishing the true association between HPV and bladder cancer is due to inadequacies of the microbiological methods used for HPV diagnosis, as suggested by Tekin et al. (6).
REFERENCES
1. Chaturvedi AK, Engels EA, Gilbert ES, et al. Second cancers among 104 760 survivors of cervical cancer: evaluation of long-term risk. J Natl Cancer Inst (2007) 99(21):1634–1643.
2. Gillison ML, Shah KV. Chapter 9: role of mucosal human papillomavirus in nongenital cancers. J Natl Cancer Inst Monogr (2003) 31:57–65.
3. Cai T, Mazzoli S, Mondaini N, Bartoletti R. Human papilloma virus DNA and p53 mutation analysis on bladder washes in relation to clinical outcome of bladder cancer. Eur Urol—Paula M.J. Moonen, Judith M.J.E. Bakkers, Lambertus A.L.M. Kiemenay, et al, eds. (2008) 53(4):858–859.[CrossRef][Medline]
4. Fioriti D, Pietropaolo V, Dal Forno S, Laurenti C, Chiarini F, Degener AM. Urothelial bladder carcinoma and viral infections: different association with human polyomaviruses and papillomaviruses. Int J Immunopathol Pharmacol (2003) 16(3):283–288.[Web of Science][Medline]
5. Massimi P, Shai A, Lambert P, Banks L. HPV E6 degradation of p53 and PDZ containing substrates in an E6AP null background [published online ahead of print October 15, 2007]. Oncogene. 101038/sj.onc.1210810.
6. Tekin MI, Tuncer S, Aki FT, Bilen CY, Aygün C, Ozen H. Human papillomavirus associated with bladder carcinoma? Analysis by polymerase chain reaction. Int J Urol (1999) 6(4):184–186.[CrossRef][Web of Science][Medline]
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J Natl Cancer Inst 2008 100: 600-601.
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