Non-Aids defining cancers

Introduction

HIV significantly increases the risk of developing cancer during ones lifetime especially since HAART has prolonged the survival of these patients and almost 1/3rd of the HIV infected are likely to develop cancer at some stage in their illness. AIDS-defining cancers are Kaposi's sarcoma, non-Hodgkin's lymphoma, and invasive cervical cancer and are the most common cancers afflicting this patient subset. Hodgkin's lymphoma, anal carcinoma, multiple myeloma, leukemia ,lung cancer, oral cancers, cancers of esophagus, prostate,skin,stomach, liver, pancreas, larynx, heart,vulva, vagina, kidney, and soft tissues also show an increased prevalence in this group and are referred to as Non-AIDS-defining cancers. Unlike the AIDS-defining malignancies, immunosuppression as a definitive cause has not been established. Viral co-infections eg human papilloma virus have been postulated as an etiology. Highly active antiretroviral therapy (HAART) has resulted in decreased mortality and it needs to be determined if availability of these medication has altered the incidence of cancer in this group of people.

Hodgkin's Disease (HD)    Those infected with HIV are 7.6 to 11.5 times more likely to have HD compared to the general population. Some studies have shown a correlation between immunosuppression and higher incidence of HD. HD tends to occur early in HIV infection when CD4 T cell counts are higher and immune competence is still intact. Studies have shown no difference in rates either when comparing patients who had received HAART with treatment-naïve patients or when comparing HD rates during the pre-HAART and post-HAART eras.

Anal cancer     There is a strong association of anal cancer and precancerous anal lesions with HPV infection. High-grade forms of these lesions have been demonstrated to be associated with the oncogenic types of HPV( HPV-16 and HPV-18).Studies indicate that those infected with HIV are 30 to 50 times more likely to have anal cancer. Progression to high-grade dysplasia is increased in the presence of HIV infection and anal HPV infection and high-grade anal precancerous lesions are extremely common. Recent data indicates that anal HPV infection can be acquired through means other than anal intercourse in HIV-positive men. For patients with untreated invasive anal cancer without evidence of distant metastases and CD4 counts >200 cells/mm3, clinicians should generally administer combined modality therapy with concurrent radiation and combination chemotherapy. Combined modality therapy (CMT) should also be considered in patients with untreated invasive anal cancer with more severe immunosuppression; however, abdominal perineal resection is an alternative treatment in such patients.

Lung cancer     HIV infected are 2.5 to 7.5 times more likely to develop lung cancer compared to HIV-negative people. Lung cancer was the most frequently observed non-AIDS-defining malignancy in several studies. Before the introduction of HAART, rates of lung cancer were low, perhaps on account of early AIDS-related mortality. A recent analysis showed an almost 9-fold increase in lung cancer incidence following the introduction of HAART.

Testicular Germ Cell Tumors     Studies show that HIV-positive men are 1.4 to 8.2 times more likely to develop testicular cancer. Viruses such as mumps orchitis, HPV, Epstein-Barr virus (EBV), and human endogenous retrovirus K10 are associated with testicular cancer in HIV-negative men and may be involved in development of testicular cancer in the HIV-positive population.

Leiomyosarcoma and Leiomyoma in Children with HIV Infection     Smooth muscle tumors are rare in children, but leiomyomas and leiomyosarcomas are unusually common in HIV-infected children, and are therefore included in the revised CDC classification of pediatric HIV disease as a Category B symptom.

The HOPS Study (HIV Outpatient Study)     evaluated cancer incidence rates over an 11 year period between 1992 and 2002. HIV-infected patients in HOPS were twice as likely to have lung cancer, 5 times more likely to have Hodgkin's disease, 10 times as likely to have anorectal cancer, and 3 times more likely to have melanoma. The risks of lung cancer, Hodgkin's disease, anorectal cancer, melanoma, and head and neck cancer were increased by 4-, 77-, 5-, 4-, and 10-fold, respectively. It concluded that the incidence of 5 Non-AIDS Cancers (lung cancer, head and neck cancer, Hodgkin's disease,anorectal cancer and melanoma) was higher in HIV infected and that CD4 nadir was associated with risk

ABSTRACTS

1. Incidence and risk factors for the occurrence of non-AIDS-defining cancers among human immunodeficiency virus-infected individuals. Burgi A, Brodine S, Wegner S, Milazzo M, Wallace MR, Spooner K, Blazes DL, Agan BK, Armstrong A, Fraser S, Crum NF. Cancer. 2005 Oct 1;104(7):1505-11

BACKGROUND: The objective of this study was to determine the rates and predictors of non-AIDS-defining cancers (NADCs) among a cohort of human immunodeficiency virus (HIV)-infected individuals. METHODS: The authors conducted a retrospective study of 4144 HIV-infected individuals who had 26,916 person-years of follow-up and who had open access to medical care at 1 of the United States military HIV clinics during the years 1988-2003. Cancer incidence rates were race specific and were adjusted for age; these were compared with national rates using logistic regression to assess predictors of NADC development. RESULTS: One hundred thirty-three NADCs were diagnosed with a rate of 980 diagnoses per 100,000 person-years. The most frequent NADCs were skin carcinomas (basal cell and squamous cell), Hodgkin disease, and anal carcinoma. The results showed that there were higher rates of melanoma, basal and squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin disease among the HIV-infected cohort compared with age-adjusted rates for the general United States population. Predictors of NADCs included age older than 40 years (odds ratio [OR], 12.2; P < 0.001), Caucasian/non-Hispanic race (OR, 2.1; P < 0.001), longer duration of HIV infection (OR, 1.2; P < 0.001), and a history of opportunistic infection (OR, 2.5; P < 0.001). The use of highly active antiretroviral therapy (HAART) was associated with lower rates of NADCs (OR, 0.21; P < 0.001). A low CD4 nadir or CD4 count at diagnosis (< 200 cells/mL) was not predictive of NADCs. CONCLUSIONS: The most frequent NADCs were primary skin malignancies. Melanoma, basal and squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin disease occurred at higher rates among HIV-infected individuals. The implementation of screening programs for these malignancies should be considered. Most risk factors for the development of NADCs are nonmodifiable; however, the use of HAART appeared to be beneficial in protecting against the development of malignant disease.

2. Immune deficiency and risk for malignancy among persons with AIDS. Mbulaiteye SM, Biggar RJ, Goedert JJ, Engels EA. J Acquir Immune Defic Syndr. 2003 Apr 15;32(5):527-33.

BACKGROUND: People with AIDS have an elevated risk for cancer. We studied the relationship between cancer risk and AIDS-related immunosuppression as measured by CD4 count at AIDS onset. METHODS: We linked records from AIDS and cancer registries in 11 US regions (1990-1996). We studied 82,217 (86.6%) adults who had a CD4 count measured at AIDS onset and survived into the follow-up period. We calculated standardized incidence ratios (SIRs) for AIDS-defining (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL] and cervical cancer) as well as non-AIDS-defining cancers in the 2 years after AIDS onset. For each cancer, the change in SIRs across CD4 counts (0-49 cells/mm3, 50-99 cells/mm3, 100-199 cells/mm3, and > or =200 cells/mm3) was modeled using Poisson regression. RESULTS: The SIRs for KS, NHL, and cervical cancer were 258, 78, and 8.8, respectively. For each fall of 100 CD4 cells/mm3, RRs were 1.36 (95% CI: 1.29-1.43) for KS and 1.48 (95% CI: 1.37-1.59) for NHL. Among NHL subtypes, the association with lower CD4 counts was strongest for immunoblastic lymphoma (RR =1.64, 95% CI: 1.37-1.96, per decline of 100 CD4 cells/mm3) and central nervous system lymphoma (RR = 2.29, 95% CI: 1.95-2.69). The SIR for cervical cancer did not vary with CD4 count (p =.74). For non-AIDS-defining cancers (overall SIR = 2.1), neither the combined risk nor the risk of specific types was associated with declining CD4 counts. CONCLUSION: SKS and NHL risk increased with level of immunosuppression at AIDS onset. Risks for other cancers, including cervical cancer, were unrelated to CD4 counts. Elevated risks for non-AIDS cancers may be a result of lifestyle factors.
3. Association of cancer with AIDS-related immunosuppression in adults. Frisch M, Biggar RJ, Engels EA, Goedert JJ; AIDS-Cancer Match Registry Study Group. JAMA. 2001 Apr 4;285(13):1736-45.

CONTEXT: Large-scale studies are needed to determine if cancers other than Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer occur in excess in persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). OBJECTIVES: To examine the general cancer pattern among adults with HIV/AIDS and to distinguish immunosuppression-associated cancers from other cancers that may occur in excess among persons with HIV/AIDS. DESIGN, SETTING, AND SUBJECTS: Analysis of linked population-based AIDS and cancer

AND SUBJECTS: Analysis of linked population-based AIDS and cancer registry data from 11 geographically diverse areas in the United States, including 302 834 adults aged 15 to 69 years with HIV/AIDS. The period of study varied by registry between 1978 and 1996. MAIN OUTCOME MEASURE: Relative risks (RRs) of cancers, calculated by dividing the number of observed cancer cases by the number expected based on contemporaneous population-based incidence rates. We defined cancers potentially influenced by immunosuppression by 3 criteria: (1) elevated overall RR in the period from 60 months before to 27 months after AIDS; (2) elevated RR in the 4- to 27-month post-AIDS period; and (3) increasing trend in RR from before to after AIDS onset. RESULTS: Expected excesses were observed for the AIDS-defining cancers, but non-AIDS-defining cancers also occurred in statistically significant excess (n = 4422; overall RR, 2.7; 95% confidence interval [CI], 2.7-2.8). Of individual cancers, only Hodgkin disease (n = 612; RR, 11.5; 95% CI, 10.6-12.5), particularly of the mixed cellularity (n = 217; RR, 18.3; 95% CI, 15.9-20.9) and lymphocytic depletion (n = 36; RR, 35.3; 95% CI, 24.7-48.8) subtypes; lung cancer (n = 808; RR, 4.5; 95% CI, 4.2-4.8); penile cancer (n = 14; RR, 3.9; 95% CI, 2.1-6.5); soft tissue malignancies (n = 78; RR, 3.3; 95% CI, 2.6-4.1); lip cancer (n = 20; RR, 3.1; 95% CI, 1.9-4.8); and testicular seminoma (n = 115; RR, 2.0; 95% CI, 1.7-2.4) met all 3 criteria for potential association with immunosuppression. CONCLUSION: Although occurring in overall excess, most non-AIDS-defining cancers do not appear to be influenced by the advancing immunosuppression associated with HIV disease progression. Some cancers that met our criteria for potential association with immunosuppression may have occurred in excess in persons with HIV/AIDS because of heavy smoking (lung cancer), frequent exposure to human papillomavirus (penile cancer), or inaccurately recorded cases of Kaposi sarcoma (soft tissue malignancies) in these persons. However, Hodgkin disease, notably of the mixed cellularity and lymphocytic depletion subtypes, and possibly lip cancer and testicular seminoma may be genuinely influenced by immunosuppression.

4. Risk of cancer in children with AIDS. AIDS-Cancer Match Registry Study Group. Biggar RJ, Frisch M, Goedert JJ. JAMA. 2000 Jul 12;284(2):205-9.

CONTEXT: Population-based data on cancers associated with acquired immunodeficiency syndrome (AIDS) in children are lacking. OBJECTIVE: To determine risk of pediatric AIDS-associated cancers. DESIGN, SETTING, AND PARTICIPANTS: Using records from 11 locations in the United States for varying periods between 1978 and 1996, we linked data for children aged 14 years and younger at AIDS diagnosis to local cancer registry data. MAIN OUTCOME MEASURES: Cancer frequency and, in the 2-year post-AIDS onset period, cancer incidence and relative risk (RR; measured as standardized incidence ratio), by cancer type. RESULTS: Among 4954 children with AIDS, 124 (2.5%) were identified as having cancer before, at, or after AIDS onset, including 100 cases of non-Hodgkin lymphoma (NHL), 8 of Kaposi sarcoma (KS), 4 of leiomyosarcoma, and 2 of Hodgkin disease; there were 10 other or unspecified cancers. Expected numbers for all cancers identified in the study sample, based on population rates (using area-specific registry data), were less than 1. In the first 2 years after AIDS diagnosis (5485 person-years), NHL incidence was 510 per 100,000 person-years (RR, 651; 95% confidence interval [CI], 432-941). Median time for developing NHL after AIDS diagnosis was 14 months (range, 3-107 months). The most common type of NHL was Burkitt lymphoma. However, the risk of primary brain lymphoma (91 per 100,000 person-years) was especially high (RR, 7143; 95% CI, 2321-16,692), and 4 cases were diagnosed more than 2 years (range, 37-98 months) after AIDS onset. Leiomyosarcomas also tended to occur several years after AIDS onset, with 3 of the 4 cases occurring 33 to 76 months after AIDS diagnosis, whereas KS was reported only at or within 2 years of AIDS diagnosis. Hodgkin disease risk was also significantly increased (RR, 62; 95% CI, 2-342). CONCLUSIONS: The spectrum of AIDS-associated pediatric cancers resembled that seen in adults, with the addition of leiomyosarcoma. Both primary brain lymphomas and leiomyosarcomas tended to occur in children surviving several years after AIDS onset. Because the expected numbers of these cancers in this population were less than 1 and because of the small numbers of some types of observed cancers, the RR estimates are imprecise and caution is warranted in their interpretation.

5. HIV-related lung cancer in the era of highly active antiretroviral therapy. Bower M, Powles T, Nelson M, Shah P, Cox S, Mandelia S, Gazzard B. AIDS. 2003 Feb 14;17(3):371-5.

OBJECTIVES: To address the impact of highly active antiretroviral therapy (HAART) on the incidence and outcome of patients with HIV-related lung cancer. DESIGN AND SUBJECTS: Patients with HIV-related lung cancer were identified from a prospective HIV data base of 8400 patients diagnosed between 1986 and 2001. Patients diagnosed with HIV-related lung cancer before 1996 were in the pre-HAART cohort whereas the remainder were in the post-HAART cohort. METHODS: The incidence of HIV-related lung cancer in the pre- and post-HAART cohorts was compared with the age and sex-matched population of south east England. Clinicopathological features, treatments and outcomes were also recorded. RESULTS: The incidence of HIV-related lung cancer increased from 0.8 (95% CI 0.2-3.2)/10(5) patient-years follow-up in the pre-HAART era to 6.7 (95% CI 3.1-13.9)/10(5) patient-years follow-up in the post-HAART era. The age and sex-matched incidence of lung cancer in south east England was 0.75 (95% CI 0.63-0.87)/10(5) patient-years, suggesting that HIV-related lung cancer only occurred more frequently in the post-HAART era (relative risk 8.93, 95% CI 4.92-19.98). The patient characteristics and outcomes were similar in the pre- and post-HAART eras, although the time interval between testing HIV positive and developing HIV-related lung cancer was longer in post-HAART patients. CONCLUSION: In this study HIV-related lung cancer occurred more frequently in the post-HAART era, when compared with the HIV-negative population. Unfortunately, the outcome of these patients remains poor despite HAART.

6. Lung carcinoma in 36 patients with human immunodeficiency virus infection. The Italian Cooperative Group on AIDS and Tumors. Tirelli U, Spina M, Sandri S, Serraino D, Gobitti C, Fasan M, Sinicco A, Garavelli P, Ridolfo AL, Vaccher E. Cancer. 2000 Feb 1;88(3):563-9.

BACKGROUND: The current study describes the clinicopathologic characteristics of 36 patients with lung carcinoma and human immunodeficiency virus (HIV) infection observed within the Italian Cooperative Group on AIDS and Tumors (GICAT). METHODS: Patients with lung carcinoma and HIV infection collected by the GICAT between 1986-1998 were evaluated retrospectively. As a control group, the authors analyzed 102 patients age < 60 years with lung carcinoma but without HIV

analyzed 102 patients age < 60 years with lung carcinoma but without HIV infection who were seen at the CRO, National Cancer Institute, Aviano, Italy between 1995-1996. RESULTS: Patients with lung carcinoma and HIV infection were younger (38 years vs. 53 years) and previously smoked more cigarettes per day (40 vs. 20) than the control group. The main histologic subtype was adenocarcinoma. TNM Stage III-IV disease was observed in 53% of the patients. The median CD4 cell count was 150/mm(3). The median overall survival was significantly shorter in the patients with HIV compared with the control group (5 months vs. 10 months; P = 0.0001). CONCLUSIONS: The results of the current study demonstrate that lung carcinoma in the HIV setting affects mainly young individuals with a history of heavy tobacco smoking and a moderately advanced immunodeficiency status. Lung carcinoma is associated with a more adverse outcome in HIV patients and represents the cause of death in the majority of these patients.

7. Therapy of non-small-cell lung cancer (NSCLC) in patients with HIV infection. GICAT. Cooperative Group on AIDS and Tumors. Spina  M, Sandri  S, Serraino  D, Gobitti  C, Fasan  M, Sinicco  A, Garavelli  PL, Ridolfo  A, Tirelli  U. Ann Oncol. 1999 10 Suppl 5:S87-90

Incidence and mortality of AIDS patients have significantly declined in the developed countries due to the very active anti-HIV combination therapy available today. Because of the prolongation of the survival expectancy of these patients, other non-AIDS defining tumours have been recently reported in several cohort studies with increased frequency. We want to report the clinico-pathological features and the outcome of 39 patients with lung cancer and HIV infection, collected by the Italian Cooperative Group on AIDS and Tumors (GICAT) between 1986 and December 1997. As a control group, we decided to evaluate patients, less than 60 years of age, with lung cancer but without HIV infection seen at the CRO, Aviano, during 1995 and 1996. The median age of the study group patients was 38 years (range 28-58) and 90% of them were males. Sixty-nine percent of patients were intravenous drug users and HIV infection was asymtomatic in 41% of patients. NSCLC was observed in 78% of patients, SCLC in 13% and mesothelioma in 8%. Among NSCLC, adenocarcinoma was the most frequently observed histological subtype (48%). No differences were found as regards the stage of disease at diagnosis and the histologic subtype in comparison with the control group. The median overall survival was significantly shorter for patients with HIV infection when compared to that of the control group (5 months vs. 10 months, P < 0.0001). In conclusion, the outcome of patients with SNCLC and HIV infection seems worse than that of the general population, suggesting a synergistic and/or addictive adverse effect of HIV on the outcome of lung cancer.
8. Breast cancer in women with human immunodeficiency virus infection: implications for diagnosis and therapy. El-Rayes BF, Berenji K, Schuman P, Philip PA. Breast Cancer Res Treat. 2002 Nov;76(2):111-6.

The rising incidence of the human immunodeficiency virus (HIV) infection in women and the prolonged survival increases the risk of development of breast cancer in this population. Through December 2001, 38 cases of breast cancer, two occurring in men, have been reported in persons infected with HIV. Between 1995 and 2001, five HIV infected premenopausal women presented with breast cancer to the Karmanos Cancer Institute. Three patients presented 3-5 years after the diagnosis of HIV infection. One patient presented with stage IV breast cancer, three with stage III, and one with stage II disease. Chemotherapy-induced myelosuppression was pronounced in all patients. Two patients had progression of HIV on treatment manifested by a rise in HIV-1 RNA or development of opportunistic infections. In general, the outcome of breast cancer in our small series of patients was worse than in a non-HIV population. HIV infection may influence the natural history and treatment of breast cancer.

9. Multicenter study of human immunodeficiency virus-related germ cell tumors. Powles T, Bower M, Daugaard G, Shamash J, De Ruiter A, Johnson M, Fisher M, Anderson J, Mandalia S, Stebbing J, Nelson M, Gazzard B, Oliver T. J Clin Oncol. 2003 May 15;21(10):1922-7.

PURPOSE: Testicular germ cell tumors (GCT) occur at increased frequency in men with human immunodeficiency virus (HIV). This multicenter study addresses the characteristics of these tumors. PATIENTS AND METHODS: Patients with HIV-related GCT were identified from six HIV treatment centers. The incidence was calculated from the center with the most complete linked oncology and HIV databases. RESULTS: Thirty-five patients with HIV-related GCT were identified. The median age at GCT diagnosis was 34 years (range, 27 to 64 years). The median CD4 cell count was 315/mm3 (range, 90 to 960/mm3) at this time. The histologic classification was seminoma in 26 patients (74%) and nonseminomatous GCT in nine patients (26%). Twenty-one patients (60%) had stage I disease and 14 patients had metastatic disease. Overall six patients relapsed, three died from GCT, and seven died from HIV disease, resulting in a 2-year overall survival rate of 81%. HIV-related seminoma occurred more frequently than in the age- and sex-matched HIV-negative population, with a relative risk of 5.4 (95% confidence interval, 3.35 to 8.10); however, nonseminomatous GCT did not occur more frequently, and there was no change in the incidence of GCT since the introduction of highly active antiretroviral therapy. CONCLUSION: Testicular seminoma occurs significantly more frequently in HIV-positive men than in the matched control population. Patients with HIV-related GCTs present and should be treated in a similar manner to those in the HIV-negative population. After a median follow-up of 4.6 years, 9% of the patients died from GCT. Most of the mortality relates to HIV infection.

10. Germ cell tumors in patients infected by the human immunodeficiency virus. Fizazi  K, Amato  RJ, Beuzeboc  P, Petit  N, Bouhour  D, Thiss  A, Rebischung  C, Chevreau  C, Logothetis  CJ, Droz  JP. Cancer. 2001 Sep;92(6):1460-7

BACKGROUND: The objective of this study was to assess the natural history of the two disease courses, patient immune system tolerance, and results of therapy in human immunodeficiency virus (HIV)-infected patients with germ cell tumors (GCT). METHODS: From 1985 to 1996, 34 HIV-infected men received a diagnosis of GCT. Their charts were analyzed retrospectively. RESULTS: Sixteen patients had seminomas, and 18 had nonseminomatous GCTs (NSGCT); 71% had International Union Against and 18 had nonseminomatous GCTs (NSGCT); 71% had International Union Against Cancer (UICC), 1997 Stage I-II GCTs. At the time of chemotherapy, 69%, 6%, and 25% of patients with advanced NSGCT were in the International Germ Cell Consensus Classification (IGCCC) good, intermediate, and poor prognostic group, respectively. All except 1 of the 10 patients with advanced seminomas were in the IGCCC good prognostic group. At diagnosis of GCT, 85% of patients were classified as having asymptomatic HIV infection or only persistent generalized lymphadenectomy. The median CD4 cell count was 325/microL (range, 6-

1125). Overall, 26 patients were given chemotherapy, but the planned dose intensity was respected in only 15 (57%) patients. Severe toxic effects included febrile neutropenia in 35% of patients. During chemotherapy, zidovudine, prophylactic granulocyte colony-stimulating factor (G-CSF), and a Pneumocystis carinii prophylaxis were given in 19%, 23%, and 35% of cases, respectively. CD4 cell count decreased in 7 (64%) of 11 patients during chemotherapy. Infradiaphragmatic radiotherapy was given in 10 cases and was clinically well tolerated. At a median follow-up of 27 months (range, 3-150), 50% of patients were alive, and only 18% of patients died of GCT. Two patients developed a non-GCT malignancy while in complete remission, namely, Hodgkin disease and an acute leukemia. CONCLUSIONS: The prognosis of GCT in HIV-infected patients is mostly dictated by the HIV infection. Patients should be treated according to stage and histologic subtype, although dose reduction of chemotherapy might be necessary in approximately half of the patients. Close surveillance of neutrophil and CD4 cells counts, as well as the use of G-CSF and systematic anti-Pneumocystis carinii prophylaxis are recommended during chemotherapy. The use of highly active antiretroviral therapy during chemotherapy for GCT requires a prospective assessment

11. Aggressive squamous cell carcinomas in persons infected with the human immunodeficiency virus. Nguyen  P, Vin-Christian  K, Ming  ME, Berger  T. Arch Dermatol. 2002 Jun;138(6):758-63

OBJECTIVES: To illustrate the potential for aggressive growth of cutaneous squamous cell carcinomas (SCCs) in patients infected with the human immunodeficiency virus (HIV) and to determine the factors associated with increased morbidity and mortality from aggressive SCCs in HIV-infected patients. DESIGN: Retrospective nonrandomized case series. SETTING: University-based dermatologic referral center. PATIENTS: A consecutive sample of 10 patients infected with HIV who had “aggressive” SCC based on the following criteria: diameter larger than 1.5 cm, rapid growth rate, local recurrence, and/or evidence of metastasis. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Five patients died of metastatic SCC within 7 years of their initial diagnosis despite treatment. Human immunodeficiency virus stage and the degree of immunosuppression were not associated with increased morbidity and mortality. Patients initially undergoing combination surgery and radiation therapy or radical neck dissection had the best outcomes. CONCLUSIONS: Patients infected with HIV can develop rapidly growing cutaneous SCCs at a young age, with a high risk of local recurrence and metastasis. High-risk SCCs should be managed aggressively and not palliatively in patients infected with HIV.

12. Treatment of HIV-associated invasive anal cancer with combined chemoradiation. Cleator S, Fife K, Nelson M, Gazzard B, Phillips R, Bower M. Eur J Cancer. 2000 Apr;36(6):754-8.

There is an increased frequency of invasive anal cancer in HIV-seropositive men. Early treatment strategies in this patient group employed reduced dosages of chemotherapy or radiotherapy alone to reduce toxicity. Since 1989 we have used combined modality treatment consisting of chemotherapy 5-fluorouracil (5-FU) and mitomycin C, and concomitant radical radiotherapy to the pelvis (38-51 Gy in 20-30 fractions), with most patients receiving a perineal boost (10-18 Gy). 12 homosexual HIV-positive men have been treated. The median CD4 count at diagnosis of anal cancer was 209 cells/microl (range: 29-380 cells/microl), 5 had prior AIDS defining diagnoses. No patients had metastatic disease. Complete remissions were obtained in 9/11 evaluable patients and in 1 further patient following surgery. 2 patients relapsed both within 6 months of diagnosis. At a median follow-up of 4.8 years (range: 0.4-10 years), 4 patients have died (2 from anal cancer, 1 from treatment-related consequences and 1 from opportunistic infection in remission). Actuarial 2-year survival is 60% (95% confidence interval (CI): 29-91%). Grade 3 haematological toxicity was recorded in 3 patients, grade 4 and 5 gastrointestinal toxicity in 1 patient each and grade 3 skin toxicity in 1 patient. Radical chemoradiation may be given safely at conventional doses in HIV-positive patients, with a high complete response rate.

13. Cancer risk in elderly persons with HIV/AIDS. Biggar RJ, Kirby KA, Atkinson J, McNeel TS, Engels E; for the AIDS Cancer Match Study Group. J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):861-8.

CONTEXT: Cancer risks in persons with AIDS are increased, but risks in elderly persons with AIDS (EPWAs) have not been previously described. OBJECTIVE: To determine the profile of cancer risks in EPWAs. DATA SOURCES AND ANALYSIS: Using AIDS data from 1981-1996, 8828 EPWAs were identified (60+ years old) and their records were linked to data in local cancer registries, finding 1142 cases. Expected case numbers were derived from the cancer incidence in the population matched for age, sex, race, calendar year, and registry. RESULTS: Compared with the general population, the relative risk (RR) for Kaposi sarcoma was 545 (95% CI, 406-717) in the 2 years after AIDS onset. For non-Hodgkin lymphoma, the RR was 24.6 (7.5-80.3). No cervical cancers were reported in this interval. From 60 months before to 27 months after AIDS onset, the RR of non-AIDS-defining cancers (n = 548) was 1.3 (1.2-1.4). The cancer types occurring at significant excess during this period were similar to those in younger adults with AIDS: Hodgkin lymphoma (RR: 13.1), anal cancer (8.2), liver cancer (3.9), multiple myeloma (2.7), leukemia (2.4), and lung cancer (1.9). However, none was significantly elevated in the 2 years after the AIDS onset. Prostate cancer risk was low overall (RR: 0.8; 0.6-0.9). CONCLUSIONS: The profile of cancer risks in EPWAs generally resembled that in younger adults with AIDS, although RRs were lower because of higher background incidence rates. We speculate that prostate cancer risk was low because of reduced screening for this cancer in EPWAs.