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Cancers in HIV: immunity/ART
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HIV Infection Is Associated with an Increased Risk for Lung Cancer ..
Clinical Infectious Diseases, July 1 2007
Gregory D. Kirk,1,2 Christian Merlo,2 Peter O' Driscoll,1 Shruti H. Mehta,1 Noya Galai,1 David Vlahov,4 Jonathan Samet,1 and Eric A. Engels2,3
".....After adjusting for age, sex, smoking status, and calendar period, HIV infection was associated with increased lung cancer risk (hazard ratio, 3.6; 95% confidence interval, 1.6-7.9).....Preexisting lung disease, particularly noninfectious diseases and asthma, displayed trends for increased lung cancer risk. Illicit drug use was not associated with increased lung cancer risk. Among HIV-infected persons, smoking remained the major risk factor;... CD4 cell count and HIV load were not strongly associated with increased lung cancer risk, and trends for increased risk with use of highly active antiretroviral therapy were not significant....If the increased risk of lung cancer among HIV-infected persons is not fully explained by smoking, further mechanisms can be postulated, including (1) an oncogenic role of HIV infection itself; (2) a direct consequence of HIV-related immunosuppression and decreased immune surveillance, similar to other AIDS-defining malignancies; (3) lung damage from recurrent infections, which are more common in HIV-infected persons; or (4) an HIV-mediated increase in susceptibility to tobacco carcinogens, such as through increases in genomic instability..."
Lower CD4 Counts Boost Risk of "Non-AIDS" Cancers
Feb 25, 2007 ...
Lower CD4 counts predict death not only from AIDS-defining cancers but also from non-AIDS cancers, according to results of a 23,437-person study of the 11-cohort D:A:D collaboration [1]. Non-AIDS malignancies accounted for almost two thirds of the deaths tallied in this 1999-2005 analysis.
-- AIDS cancers caused 82 deaths from non-Hodgkin lymphoma, 28 from Kaposi sarcoma, and 2 from cervical carcinoma. Among the non-AIDS cancer deaths, 20% involved the lung and 13% the gastrointestinal (GI) tract, with about one third of GI deaths from liver cancer. Other non-AIDS cancers were hematologic (7% of deaths), anal (7%), urogenital (6%), upper respiratory (3%), and others (7%).
Elevated risk of lung cancer among people with AIDS
AIDS: Volume 21(2) 11 January 2007 p 207-213
"....The substantial lung cancer risk at younger ages coupled with an advanced stage at diagnosis suggests an acceleration of lung cancer pathogenesis among PWA....
... One possibility is that the effects of smoking could be more severe in HIV-infected individuals. Indeed, an accelerated form of smoking-related emphysema, a risk factor for lung cancer [23], also occurs among HIV-infected individuals [24]. Several lines of evidence point to altered lung function and enhanced lung damage among HIV-infected individuals. HIV infection may lead to increased oxidative stress in the lung mediated through deficiency of antioxidants such as glutathione [25]. HIV-infected individuals are also more susceptible to lung infections and pneumonia caused by a wide range of organisms such as Streptococcus pneumoniae, Chlamydia pneumoniae, Pneumocystis jirovecii, and Mycobacteria species. Repeated or chronic lung infections could increase lung cancer risk through chronic inflammation [26].
Although some of the aforementioned processes would be expected to be more severe with advancing HIV disease, the actual relationship between immunosuppression and lung cancer is uncertain...."
Incidence of Types of Cancer among HIV-Infected Persons Compared with the General Population in the United States, 1992-2003 - (05/28/08)
In the largest analyses of cancer incidence trends among HIV-infected persons in the United States, we observed significantly higher rates of several types of cancer from 1992 to 2003 among HIV-infected persons than in the general population. Non-AIDS-defining types of cancer with higher incidence rates were anal, colorectal, liver, lung, oropharyngeal, renal, and vaginal cancer; Hodgkin lymphoma; leukemia; and melanoma.......Immune dysfunction (52); concomitant infection with oncogenic viruses (53-55); and lifestyle factors, such as smoking, may account for the higher cancer incidence among HIV-infected persons....
....our findings indicate that HIV-infected persons are at higher risk than the general population for many non-AIDS-defining types of cancer. In addition to encouraging tobacco cessation, HIV care providers should be aware of these elevated risks and screen for preventable diseases, such as cervical and colorectal cancer (73-75). Screening programs for early detection and treatment of precancerous anal lesions should be evaluated and will probably become more important as the HIV-infected population ages and lives longer. Furthermore, primary prevention strategies to reduce HPV infection and HPV-associated diseases, such as vaccination and circumcision, warrant further evaluation.
.....Antiretroviral therapy was independently associated with decreased risk for Kaposi sarcoma (relative risk, 0.61; P < 0.001), non-Hodgkin lymphoma (0.68; P < 0.001), cervical cancer (0.48; P = 0.019), breast cancer (0.35; P = 0.013), colorectal cancer (0.50; P = 0.027), and lung cancer (0.52; P < 0.003). A low nadir CD4 count was associated with increased risk for Kaposi sarcoma (relative risk, 8.34; P < 0.001), non-Hodgkin lymphoma (6.03; P < 0.001), cervical cancer (3.70; P = 0.010), anal cancer (5.82; P = 0.017), colorectal cancer (6.27; P = 0.013), and lung cancer (2.42; P = 0.017). Co-infection with hepatitis B or C was associated with increased risk for liver cancer (relative risk, 3.63; P < 0.001).....
.....Immunosuppression may accelerate the progression of melanoma and other types of cancer in individuals who are already predisposed to them, as described in studies of transplant recipients (56-62). In our study, a low nadir CD4 cell count was associated with significantly increased risk for colorectal cancer, whereas use of antiretroviral therapy significantly decreased risk, suggesting that pathogenesis of colorectal cancer may be immune-mediated; this finding is consistent with previous reports (63). However, incidence rates for melanoma and colorectal cancer increased significantly across the 3 periods, suggesting a role of other contributing factors (such as behavioral or lifestyle factors).....
....To describe cancer diagnoses in persons at all stages of HIV infection, we analyzed data from 2 large prospective cohort studies in the United States: the Adult and Adolescent Spectrum of HIV Disease (ASD) Project and the HIV Outpatient Study (HOPS). We compared incidence rates of cancer among these persons with incidence rates in the general population, derived from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (44, 45) for 1992 to 2003....
....Anal cancer is the only type that increased in both incidence among HIV-infected persons and relative incidence compared with the general population over time. Although this finding is concerning, it is not surprising. The predominance of men who have sex with men among the HIV-infected population and the resultant higher prevalence of anal human papillomavirus (HPV) infection are associated with anal intraepithelial neoplasia (66, 67). The interaction between HIV and HPV allows for persistence of HPV infection in HIV-infected persons, who are more commonly infected with the oncogenic HPV subtypes 16 and 18, leading to development of dysplasia (14, 68, 69). Because HAART does not alter the incidence or progression of anal intraepithelial neoplasia (20, 70), persons who are successfully treated with HAART but are co-infected with HIV and HPV are expected to remain at greater risk for anal cancer over time and incidence rates are expected to increase as HIV-infected persons live longer.....
....Annals of Internal Medicine
20 May 2008 | Volume 148 Issue 10 | Pages 728-736
At the CROI HIV Conference in early 2008, several studies were presented showing detectable viral load and low CD4 count can contribute to the development of cancers.
"In addition to encouraging tobacco cessation, HIV care providers should be aware of these elevated risks and screen for preventable diseases, such as cervical and colorectal cancer (73-75). Screening programs for early detection and treatment of precancerous anal lesions should be evaluated and will probably become more important as the HIV-infected population ages and lives longer."
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