1266 Risk of Germ Cell Tumors among Men with HIV/Acquired Immunodeficiency Syndrome

James J. Goedert,1 Mark P. Purdue,2 Timothy S. McNeel,4 Katherine A. McGlynn,3 and Eric A. Engels1, for the HIV/AIDS Cancer Match Study 1Viral Epidemiology Branch, 2Occupational and Environmental Epidemiology Branch, and 3Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland and 4Information Management Services, Inc., Silver Spring, Maryland

Abstract

Background: Men with HIV/acquired immunodeficiency SIR, 2.1; 95% CI, 1.1-3.7). Seminoma risk was elevated syndrome (AIDS) are reported to be at increased risk for regardless of age, race, or HIV/AIDS transmission group. It germ cell tumors (GCT), particularly testicular seminoma. was highest for disseminated disease (SIR, 4.7; 95% CI, 2.9- We investigated correlates of this association to improve 7.2) and within 9 months of AIDS onset (SIR, 7.6; 95% CI, 5.8- understanding of GCTs. 9.6), but it was unrelated to CD4 count and duration of HIV/ Methods: Testicular and extratesticular seminoma and non- AIDS. The excess risk of seminoma declined in more recent seminoma cases were found by linking population-based calendar periods, and it was no longer elevated (SIR, 1.4; 95% cancer and HIV/AIDS registry data for 268,950 men who CI, 0.9-1.9) in the highly active antiretroviral treatment era. developed AIDS in 1980 to 2003. Standardized incidence Conclusions: Men with HIV/AIDS had an increased risk of ratios (SIR) with 95% confidence intervals (95% CI) were seminoma, but this risk may have attenuated with improving used to compare these cases with the number of cases anti-HIV/AIDS treatments. Although detection bias could expected in the demographically matched population. partly explain the excess of this cancer, various lines of Results: Overall, seminoma risk (161 cases: SIR, 1.9; 95% CI, evidence support a causal relationship. Possible mechanisms 1.6-2.2) was increased significantly with HIV/AIDS, whereas underlying this association include impaired tumor immu- nonseminoma risk was not (56 cases: SIR, 1.3; 95% CI, 0.96- nosurveillance or AIDS-related testicular atrophy. (Cancer 1.7). Extratesticular GCT risk also was increased (11 cases: Epidemiol Biomarkers Prev 2007;16(6):1266–9)

Introduction

In 1995, Lyter et al. (1) reported a significantly elevated risk of seminoma cases in England, median CD4 count was 294 developing testicular germ cell tumor (GCT), particularly cells/AL, suggesting that immunodeficiency was present but seminoma, in a prospective cohort of homosexual men infected not severe (4). with HIV. Similar or higher risks were found in several We examined chronologic, demographic, immunologic, and American, Australian, British, and Italian studies (2-5). The other data from 268,950 men diagnosed with HIV/AIDS in the risk may not be limited to the testis, as mediastinal malignant United States from 1980 to 2003 to better understand the risk of germinoma risk among men with the acquired immunodefi- seminoma and nonseminoma in this population. ciency syndrome (AIDS) seemed to be increased, based on two studies with very sparse data (1, 2). Remarkably, risk of nonseminoma seems unrelated to HIV/AIDS (1-6). Materials and Methods The increased risk of seminoma among men with HIV/ AIDS remains unexplained. Impairment of tumor immuno- Populations and Cancer Cases. As reported elsewhere surveillance by HIV infection has been proposed as a possible (6, 8, 9), the HIV/AIDS Cancer Match Study used a probabi- underlying mechanism (4). This hypothesis is supported listic computer algorithm based on name, sex, race, dates of birth by evidence that the extent of lymphocyte infiltration in and death, and (where available) social security number to link stage I seminoma is associated with a reduced risk of HIV/AIDS and cancer registries in seven states (Colorado, disease recurrence (7). Linkage studies in the United States Michigan, New Jersey, Massachusetts, Connecticut, Georgia, suggested that seminoma risk increased in time relative to an and Florida) and five metropolitan areas (San Francisco, Los individual’s initial AIDS-defining disease (termed AIDS- Angeles, San Diego, Seattle, and New York City). relative time), further supporting a role for immune function Among all men diagnosed with AIDS ages 15 to 92 years, (2, 6). In Australia, however, there was no association with the current study evaluated the risk of invasive seminoma AIDS-relative time (3). Moreover, among 26 HIV-related (International Classification of Diseases for Oncology, third edition M9060-9064) and nonseminomatous GCT (Internation- al Classification of Diseases for Oncology, third edition M9065, Received 1/12/07; revised 2/28/07; accepted 3/16/07. 9070-9085, 9100-9103; ref. 10). In a sensitivity analysis, codes Grant support: Intramural Research Program of the National Cancer Institute, NIH. M9063 (spermatocytic seminoma) and M9064 (germ cell not The costs of publication of this article were defrayed in part by the payment of page charges. otherwise specified) were excluded. Separate analyses were This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. done for cancers arising in the testis (International Classifica- Section 1734 solely to indicate this fact. Note: HIV/AIDS and cancer registries in the following regions participated in the HIV/AIDS tion of Diseases for Oncology, third edition C620-629) and for Cancer Match Study: the states of Colorado, Connecticut, Florida, Georgia, Massachusetts, extratesticular tumors (all other sites). Hispanic and missing/ Michigan, and New Jersey and the metropolitan areas of Los Angeles, San Diego, and other race men (n = 37 cases) were excluded due to limited San Francisco (California), New York City (New York), and Seattle (Washington). Requests for reprints: James J. Goedert, Viral Epidemiology Branch, Division of Cancer population-based incidence data for comparison. Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892. Phone: 301-435-4724. E-mail: [email protected] Statistical Analyses. Detailed statistical methods were Copyright D 2007 American Association for Cancer Research. reported elsewhere (6, 8, 9). Briefly, time at risk was doi:10.1158/1055-9965.EPI-07-0042 calculated from the start to the end of complete cancer

Cancer Epidemiol Biomarkers Prev 2007;16(6). June 2007 Downloaded from cebp.aacrjournals.org on October 2, 2021. © 2007 American Association for Cancer Research. Cancer Epidemiology,Biomarkers & Prevention 1267 registration in each area, no earlier than 60 months before Table 2. SIR of testicular seminoma among 268,590 men nor later than 120 months after AIDS onset (defined as month from 60 mo before to 120 mo after an initial AIDS-defining zero for each individual), and censored at death if earlier than event, 1980 to 2003 120 months after AIDS. As the measure of risk, we used the standardized incidence ratio (SIR), which is the ratio of Group, variable Seminoma Seminoma SIR (95% CI) cases cases observed to expected cancer cases derived from contempora- observed expected neous, race-, age-, and registry-specific population-based incidence rates. We calculated 95% confidence intervals (95% All men with AIDS 161 85.0 1.9 (1.6-2.2) CI) assuming a Poisson distribution of the observed cancers Tumor stage* P Localized 99 60.9 1.6 (1.3-2.0) (11). CI excluding unity (e.g., two-sided =0.05)was Regional 24 12.0 2.0 (1.3-3.0) considered statistically significant. A two-sided score test Distant 21 4.5 4.7 (2.9-7.2) was used to assess trends with time and CD4 count (2, 6). Unknown 14 3.6 3.8 (2.1-6.4) Testing for trend in risk by calendar year was limited to the Age at seminoma (y) <35 70 33.9 2.1 (1.6-2.6) 2 years (months +4 to +27) after AIDS onset. Risk assessments z for CD4 count (at AIDS onset) and stage by calendar year were 35 91 51.0 1.8 (1.4-2.2) Race limited to the 5 years (months +4 to +60) after AIDS onset. White 142 74.7 1.9 (1.6-2.2) Alternative restrictions on the time intervals yielded similar Black 19 10.3 1.8 (1.1-2.9) A results (not presented). All trend and subgroup analyses were CD4 count (cells/ L) c defined a priori. 0-99 8 5.9 1.3 (0.6-2.7)c 100-199 14 7.5 1.9 (1.0-3.1)c z200 3 3.1 1.0 (0.2-2.8) P Results trend = 0.84 Transmission category For matching done in 2003 to 2005, there were 268,950 men MSM 118 59.1 2.0 (1.7-2.4) IDU 12 11.3 1.1 (0.5-1.9) with AIDS (56% white, 44% black) who were followed for MSM and IDU 9 7.1 1.3 (0.6-2.4) 2,100,317 person-years (mean, 7.8 years). Like the U.S. AIDS Transfusion/hemophilia 7 0.7 9.8 (3.9-20.2) population, they had a median age of 38 years. AIDS onset Heterosexual 3 2.3 1.3 (0.3-3.8) occurred before 1990 in 22%, during 1990 to 1995 in 47%, and Other/unknown 12 4.5 2.7 (1.4-4.7) in 1996 to 2003 in 31%. There were 217 testicular GCT cases with AIDS compared NOTE: The 268,950 men, ages 15 to 92, accumulated 2,100,317 person-years, censored at death and excluding time when the population-based cancer registry with 129 cases expected (SIR, 1.7; 95% CI, 1.5-1.9; Table 1). in the same region lacked complete data. Men with AIDS had an elevated risk for testicular seminoma Abbreviations: MSM, men who had sex with men; IDU, injection drug use. (161 cases: SIR, 1.9). Their risk for testicular nonseminoma was *Excludes one registry where stage data were not obtained. marginally elevated (56 cases: SIR, 1.3; 95% CI, 0.96-1.7). cObserved and expected cases and SIR presented are for +4 to +60 mo after AIDS À Extratesticular GCT was diagnosed in 11 men with AIDS (SIR, onset, by CD4 count at AIDS (within 6 to +3 mo of AIDS onset), limited to years 2.1; 95% CI, 1.1-3.7), including 8 with seminoma (germinoma) 1990 to 2003 (10). histology (SIR, 2.5; 95% CI, 1.1-5.0) and 3 with other germ cell histologies (SIR, 1.4; 95% CI, 0.3-4.1). Exclusion of cases of who had sex with men (SIR, 2.0), who accounted for 73% of the spermatocytic seminoma or germ cell not otherwise specified cases, and in transfusion- and hemophilia-associated AIDS histologies had minimal effect on these risk estimates, (SIR, 9.8). Nonseminoma risk did not differ from that in the although the SIR for extratesticular germinoma was no longer general population for any demographic or HIV transmission statistically significant (footnote in Table 1). category (data not shown). As shown in Table 2, testicular seminoma risk was higher Seminoma risk was markedly increased (SIR, 7.6; 95% CI, for disseminated disease (SIR, 4.7) than for regional (SIR, 2.0) 5.8-9.6) near the time of AIDS onset. The risk was less elevated or localized (SIR, 1.6) disease. Seminoma risk was elevated up to 2 years before (SIR, 1.7) and after (SIR, 2.1) AIDS onset. It before age 35 (SIR, 2.1) and at or after age 35 (SIR, 1.8) and in also was not elevated more than 2 years before or after AIDS whites (SIR, 1.9) and blacks (SIR, 1.8). Seminoma risk was onset (Table 3), but these data are very sparse and could unrelated to CD4 count measured at AIDS onset based on underestimate the true risk by 15% or more due to migration sparse data. Seminoma risk was elevated significantly in men into or out of the registry area (9). Of note, across every AIDS-relative time interval, seminoma SIR declined with more recent calendar year of AIDS onset (Table 3). Considering all cases in all intervals, SIR fell from Table 1. SIR of GCT among 268,590 men from 60 mo before 3.3 to 1.7 to 1.4 with AIDS onset in 1980 to 1989, 1990 to 1995, to 120 mo after an initial AIDS-defining event, 1980 to 2003 and 1996 to 2003, respectively. For the time interval with the most complete prospective follow-up (+4 to +27 months after GCT site and histology* GCT cases GCT cases SIR (95% CI) AIDS onset), the change in SIR with calendar time was observed expected P marginally significant ( trend = 0.056; Table 3). During the +4 All testicular GCT 217 129.1 1.7 (1.5-1.9) to +60 months after AIDS onset, SIR declined over time for all Testis seminoma 161 85.0 1.9 (1.6-2.2) stages of seminoma. As shown in Table 4, from AIDS onset in Testis nonseminoma 56 44.1 1.3 (0.96-1.7) 1980 to 1989 to 1996 to 2003, seminoma local stage SIR declined Extratestis seminoma 8 3.1 2.5 (1.1-5.0) from 1.9 to 1.2; for regional stage SIR declined from 3.1 to 1.1; Extratestis other GCT 3 2.1 1.4 (0.3-4.1) and for distant stage it declined from 3.8 to 0. NOTE: The 268,950 men, ages 15 to 92, accumulated 2,100,317 person-years, censored at death and excluding time when the population-based cancer registry in the same region lacked complete data. Discussion *With exclusion of spermatocytic seminoma (M9063) and germ cell not otherwise specified (M9064) histologies, there were 155 testis seminoma observed and Compared with the general population, we found that men 82.3 expected (SIR, 1.88; 95% CI, 1.60-2.20), 56 testis nonseminoma observed and f 44.1 expected (SIR, 1.27; 95% CI, 0.96-1.65), 4 extratestis germinoma observed with AIDS had an 90% higher risk of seminoma but no and 1.2 expected (SIR, 3.29; 95% CI, 0.90-8.41), and 3 extratestis other GCT significant difference in risk of nonseminoma. Seminoma risk observed and 1.9 expected (SIR, 1.56; 95% CI 0.32-4.55). was highest with AIDS onset during the 1980s, when little or

Cancer Epidemiol Biomarkers Prev 2007;16(6). June 2007 Downloaded from cebp.aacrjournals.org on October 2, 2021. © 2007 American Association for Cancer Research. 1268 Testis Cancer Risk among Men with AIDS

Table 3. SIR of testicular seminoma among men with AIDS, by AIDS-relative time and calendar year of AIDS onset c AIDS-relative time interval (mo)* Calendar year of AIDS onset SIR (95% CI) for all years

1980-1989 1990-1995 1996-2003

Obs. SIR Obs. SIR Obs. SIR À60 to À25 7 1.3 9 0.7 4 0.4 0.7 (0.4-1.1) À24 to À7 12 3.7 9 1.2 6 1.2 1.7 (1.1-2.5) À 6 to +3b 20 10.4 30 7.0 15 6.3 7.6 (5.8-9.6) +4 to +27 10 3.4 15 2.0 5 1.3 2.1 (1.4-3.0) +28 to +60 2 1.4 6 0.9 3 1.0 1.0 (0.5-1.8) +61 to +120 2 1.7 6 1.1 0 0 1.0 (0.5-2.2) All AIDS-relative time intervals: 53 3.3 75 1.7 33 1.4 1.9 (1.6-2.2) (95% CI for SIR) (2.5-4.3) (1.3-2.1) (0.9-1.9)

Abbreviation: Obs., number of seminoma cases observed. *AIDS-relative time intervals are as follows: distant pre-AIDS (À60 to À25), later pre-AIDS (À24 to À7), at AIDS onset (À6 to +3), shortly after AIDS onset (+4 to +27), later after AIDS onset (+28 to +60), and very late after AIDS onset (+61 to +120). cCalendar years of AIDS onset correspond to anti-HIV therapy as follows: little or no antiretroviral therapy (1980-1989), availability of single and dual nucleoside reverse transcriptase inhibitors (1990-1995), and availability of HAART combinations (1996-2003). bP trend = 0.056 for SIR across the three calendar year periods. no antiretroviral therapy was available, and it was less renal transplantation remains largely undefined due to sparse elevated during the early 1990s, when single and dual data (22, 23). nucleoside reverse transcriptase therapy was widely used. In AIDS, testicular atrophy is thought to be due to the With AIDS onset during the highly active antiretroviral general debilitating effects of the disease rather than due to therapy (HAART) era (8, 9), starting in 1996, seminoma risk specific immune, hormonal, or infectious disorders or treat- did not differ from that in the general population. However, ments (16, 17, 21). Improving anti-HIV treatments was this attenuation of the elevated risk with improving anti-HIV associated with a decreased prevalence of spermatogenic therapy was not mirrored by associations with CD4 count or arrest, which declined from 48% among men who died of AIDS-relative time. Although risk was not related to these AIDS in 1981 to 1987 to 28% among AIDS decedents in 1988 to measures of immune function, the trends in seminoma risk 1995 (18). Two (29%) of seven AIDS decedents in the HAART could still be related to other changes in the AIDS population. era also had spermatogenic arrest (18). It is possible that Seminoma risk was increased with transfusion- and hemo- testicular dysgenesis in men with HIV/AIDS predisposed philia-associated HIV/AIDS, arguing that it was not related to them to developing testicular GCT and that effective HIV sexually acquired infections or male homosexuality. Scanty treatments have prevented this precursor condition. evidence has been found that mumps virus, parvovirus B19, or In addition to a high prevalence of testicular dysgenesis herpes viruses contribute to testicular cancer risk (12, 13), but with AIDS, it may be that tumor-infiltrating lymphocytes are possible associations in the setting of HIV/AIDS have not been deficient with untreated HIV infection. Tumor-infiltrating investigated. lymphocytes correlate directly with better seminoma progno- Men with HIV/AIDS are not known to have an increased sis (4, 7, 24, 25). For men with HIV/AIDS, we found that prevalence of cryptorchidism, polythelia, hypospadias, or seminoma risk was significantly higher for disseminated than gonadal differentiation disorders associated with testicular for earlier stages. This finding indicates a shift toward cancer (13-15). In contrast, the majority of men dying of AIDS metastatic behavior of seminomas among men with HIV/ do have testicular atrophy (16, 17) and more specifically AIDS. We speculate that a deficit of tumor-infiltrating hypospermatogenesis, spermatogenic arrest, or a Sertoli-cell- lymphocytes in untreated HIV infection accounts for this shift only testicular histology (18). These pathologic abnormalities and may also increase the risk of seminoma and perhaps also are seen adjacent to a GCT or in the contralateral testis extratesticular germinoma as well. We further speculate that of men with GCT, supporting the hypothesis that they are a recovery of tumor-infiltrating lymphocyte activity with im- manifestation of a premalignant testicular dysgenesis syn- proving anti-HIV treatments might account for the attenuation drome (19, 20). Unlike with congenital conditions, testicular of seminoma risk during the 1990s. atrophy among men with AIDS has occurred after puberty. Our findings are subject to bias. AIDS-associated seminoma Some adult men with chronic renal failure have testicular risk was markedly increased for diagnosis within a few atrophy (21), but the risk of testicular cancer before and after months of AIDS onset, pointing to an effect of screening. In

Table 4. SIR of testicular seminoma during 4 to 60 mo after AIDS onset, by stage and calendar year of AIDS onset c Stage* Calendar year of AIDS onset

1980-1989 1990-1995 1996-2003

Obs. Exp. SIR Obs. Exp. SIR Obs. Exp. SIR Localized 6 3.1 1.9 17 9.7 1.7 6 5.1 1.2 Regional 2 0.6 3.1 3 2.0 1.5 1 0.9 1.1 Distant 1 0.3 3.8 1 0.8 1.2 0 0.4 0 Unknown 2 0.2 8.6 0 0.6 0 0 0.2 0

Abbreviation: Exp., number of seminoma cases expected. *Excludes one registry where stage data were not obtained. cCalendar years of AIDS onset correspond to anti-HIV therapy as follows: little or no antiretroviral therapy (1980-1989), availability of single and dual nucleoside reverse transcriptase inhibitors (1990-1995), and availability of HAART combinations (1996-2003).

Cancer Epidemiol Biomarkers Prev 2007;16(6). June 2007 Downloaded from cebp.aacrjournals.org on October 2, 2021. © 2007 American Association for Cancer Research. Cancer Epidemiology,Biomarkers & Prevention 1269 contrast to seminoma, nonseminoma may be less affected by 6. Frisch M, Biggar RJ, Engels EA, Goedert JJ. Association of cancer with AIDS- related immunosuppression in adults. JAMA 2001;285:1736 – 45. screening bias because nonseminoma may be less indolent and 7. Parker C, Milosevic M, Panzarella T, et al. The prognostic significance of the thus less likely to be diagnosed incidentally (26). However, an tumour infiltrating lymphocyte count in stage I testicular seminoma accelerated diagnosis of indolent seminoma at AIDS onset managed by surveillance. Eur J Cancer 2002;38:2014 – 9. would not account for the continuing excess that we observed 8. Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS 2006;20:1645 – 54. during the 2 years after AIDS onset. Moreover, the stronger 9. Goedert JJ, Schairer C, McNeel TS, Hessol NA, Rabkin CS, Engels EA. Risk risk observed for disseminated testicular cancer is incompat- of breast, ovary, and uterine corpus cancers among 85,268 women with ible with screening bias. Finally, if screening bias was AIDS. Br J Cancer 2006;4:642 – 8. substantial, the increased intensity and frequency of monitor- 10. Fritz A, Percy C, Jack A, et al. International classification of diseases for oncology. 3rd ed. Geneva: World Health Organization; 2000. ing of HIV/AIDS patients during the 1990s and into the 11. Breslow NE, Day NE. Statistical methods in cancer research. Volume II—The HAART era should have increased, rather than decreased, the design and analysis of cohort studies. IARC Sci Publ; 1987. p. 1 – 406. apparent risk of seminoma. 12. McGlynn KA. Environmental and host factors in testicular germ cell tumors. In summary, our analysis of f40% of the non-Hispanic U.S. Cancer Invest 2001;19:842 – 53. 13. Garner MJ, Turner MC, Ghadirian P, Krewski D. Epidemiology of testicular population with AIDS revealed that testicular seminoma risk cancer: an overview. Int J Cancer 2005;116:331 – 9. was increased significantly, whereas nonseminoma risk was 14. Schottenfeld D. Testicular cancer. In: Schottenfeld D, Fraumeni JF Jr, editors. not. The increased risk was no longer apparent in recent years, Cancer epidemiology and prevention, chapter 56. New York: Oxford perhaps because of overall clinical and immunologic improve- University Press; 1996. p. 1207 – 19. 15. Goedert JJ, McKeen EA, Javadpour N, Ozols RF, Pottern LM, Fraumeni JF, ment with HAART. Follow-up data from large populations of Jr. Polythelia and testicular cancer. Ann Intern Med 1984;101:646 – 7. men with HIV/AIDS may help to clarify these associations 16. Leibovitch I, Goldwasser B. The spectrum of acquired immune deficiency with testicular cancer. syndrome-associated testicular disorders. Urology 1994;44:818 – 24. 17. De Paepe ME, Waxman M. Testicular atrophy in AIDS: a study of 57 autopsy cases. Hum Pathol 1989;20:210 – 4. Acknowledgments 18. Shevchuk MM, Pigato JB, Khalife G, Armenakas NA, Fracchia JA. Changing We thank the staff members of the above-mentioned registries who testicular histology in AIDS: its implication for sexual transmission of HIV. collected the data, prepared data files for the matches, and facilitated Urology 1999;53:203 – 8. 19. Hoei-Hansen CE, Holm M, Rajpert-De Meyts E, Skakkebaek NE. Histolo- the record linkages; Phil Virgo (Computer Sciences Corp., Rockville, gical evidence of testicular dysgenesis in contralateral biopsies from 218 MD) for doing the record linkages; Norma Kim, Emily Moser, and patients with testicular germ cell cancer. J Pathol 2003;200:370 – 4. Christopher McClure (RTI International, Rockville, MD) for study 20. Nistal M, Gonzalez-Peramato P, Regadera J, Serrano A, Tarin V, De Miguel management; and Dr. Robert Biggar for helpful discussions and review MP. Primary testicular lesions are associated with testicular germ cell of the manuscript. tumors of adult men. Am J Surg Pathol 2006;30:1260 – 8. 21. Handelsman DJ, Dong Q. Hypothalamo-pituitary gonadal axis in chronic renal failure. Endocrinol Metab Clin North Am 1993;22:145 – 61. 22. Vajdic CM, McDonald SP, McCredie MR, et al. Cancer incidence before and References after kidney transplantation. JAMA 2006;296:2823 – 31. 1. Lyter DW, Bryant J, Thackeray R, Rinaldo CR, Kingsley LA. Incidence of 23. Birkeland SA, Storm HH, Lamm LU, et al. Cancer risk after renal human immunodeficiency virus-related and nonrelated malignancies in a transplantation in the Nordic countries, 1964-1986. Int J Cancer 1995;60: large cohort of homosexual men. J Clin Oncol 1995;13:2540 – 6. 183 – 9. 2. Goedert JJ, Cote TR, Virgo P, et al. Spectrum of AIDS-associated malignant 24. Nakanoma T, Nakamura K, Deguchi N, Fujimoto J, Tazaki H, Hata J. disorders. Lancet 1998;351:1833 – 9. Immunohistological analysis of tumour infiltrating lymphocytes in semi- 3. Grulich AE, Li Y, McDonald A, Correll PK, Law MG, Kaldor JM. Rates of noma using monoclonal antibodies. Virchows Arch A Pathol Anat non-AIDS-defining cancers in people with HIV infection before and after Histopathol 1992;421:409 – 13. AIDS diagnosis. AIDS 2002;16:1155 – 61. 25. Yakirevich E, Lefel O, Sova Y, et al. Activated status of tumour- 4. Powles T, Bower M, Daugaard G, et al. Multicenter study of human infiltrating lymphocytes and apoptosis in testicular seminoma. J Pathol 2002; immunodeficiency virus-related germ cell tumors. J Clin Oncol 2003;21: 196:67 – 75. 1922 – 7. 26. Powles TB, Bhardwa J, Shamash J, Mandalia S, Oliver T. The changing 5. Gabutti G, Vercelli M, De Rosa MG, et al. AIDS related neoplasms in Genoa, presentation of germ cell tumours of the testis between 1983 and 2002. BJU Italy. Eur J Epidemiol 1995;11:609 – 14. Int 2005;95:1197 – 200.

Cancer Epidemiol Biomarkers Prev 2007;16(6). June 2007 Downloaded from cebp.aacrjournals.org on October 2, 2021. © 2007 American Association for Cancer Research. Risk of Germ Cell Tumors among Men with HIV/Acquired Immunodeficiency Syndrome

James J. Goedert, Mark P. Purdue, Timothy S. McNeel, et al.

Cancer Epidemiol Biomarkers Prev 2007;16:1266-1269.

Updated version Access the most recent version of this article at: http://cebp.aacrjournals.org/content/16/6/1266

Cited articles This article cites 23 articles, 2 of which you can access for free at: http://cebp.aacrjournals.org/content/16/6/1266.full#ref-list-1

E-mail alerts Sign up to receive free email-alerts related to this article or journal.

Reprints and To order reprints of this article or to subscribe to the journal, contact the AACR Publications Subscriptions Department at [email protected].

Permissions To request permission to re-use all or part of this article, use this link http://cebp.aacrjournals.org/content/16/6/1266. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC) Rightslink site.

Downloaded from cebp.aacrjournals.org on October 2, 2021. © 2007 American Association for Cancer Research.