Named after Dr. Moritz Kaposi who first described the condition in 1872, Kaposi’s sarcoma has been with us for many years. Until the 1980s, the sarcoma (a cancer that effects the connective tissue such as bone, cartilage, fat, muscle, blood vessels and ligaments) was considered a rare disease. In the past it occurred in three main populations: elderly men of Mediterranean or Jewish heritage, organ transplant recipients receiving immune suppression therapy, and young people in Africa (American Cancer Association, 2006). It will probably strike you that these are not populations that typically use nitrites. With the advent of AIDS, Kaposi’s sarcoma reached epidemic proportions in the homosexual male population. Prior to the AIDS epidemic, the cancer occurred in only 0.02 to 0.06 individuals per 100,000 (Oettle 1962). By 1984, never-married men in the San Francisco area were 2000 times more likely to develop the disease than they were in the previous decades (Williams et al. 1994). Fortunately, as new AIDS treatments evolved, the number of cases of Kaposi’s sarcoma has fallen by about 85% (American Cancer Association 2006). These numbers and dates are interesting as they correspond directly with the emergence and treatment of the HIV virus, not with use of poppers, which was at it height in the 1960s and 1970s, prior to the AIDS epidemic (Lau et al. 1992; Stall and Purcell 2000) Scientists suggesting a connection between KS and alkyl nitrites often refer to the fact that KS occurs about 20 times more frequently in homosexual men with AIDS than in heterosexual individuals suffering from the disease (Beral 1989), citing that these findings support the hypothesis that alkyl nitrites may be a cofactor of KS (Wikipedia 2006). While the hypothesis is interesting, I find continued claims of this nature surprising, considering that they were refuted by the MACS study (reviewed earlier in the text) in 1987 (Polk et al. 1987), among other studies (Voeller 1990). In fact, researchers from the Johns Hopkins School of Hygiene and Public Health reanalyzed data from the MACS study and actually found that higher use of alkyl nitrites corresponded with lower incidence of KS (Palenicek et al. 1992).
This leaves us with the million-dollar question: If alkyl nitrites are not causing KS, >what is? Many recent studies support the hypothesis that KS is caused by a sexually transmitted herpes virus, HHV-8, also called KSHV (Kaposi’s Sarcoma Associated Herpes Virus) (Whitby et al. 1995; Ziegler and Katongole-Mbidde 1996; Gnann et al. 2000). This hypothesis supports data that shows a low prevalence of KS among intravenous drug users and blood product recipients suffering from AIDS, as these individuals typically contract HIV through non-sexual (blood to blood) means. As a herpes virus, HHV-8 travels through nerve endings, and although it is sexually transmissible, it is unlikely to be transmitted through the blood (Gnann et al. 2000). Many studies support the HHV-8 hypothesis. As early as 1989, the Centers for Disease Control recognized that if an infectious agent caused KS, it was likely transmitted by some form of homosexual contact rather than by blood (Beral 1989). Six years later in a 1995 study by Whitby et al., HHV-8 was consistently detected in the biopsy samples of patients with both AIDS related and non-AIDS related (classical) KS. Further, HHV-8 was detected in the blood cells of over half of the KS patients, but not in those of the non-KS patients used as controls. Further studies support these findings (Bobroski et al. 1998; Gnann et al. 2000). In a 1996, study of children in Uganda published in the International Journal of Cancer, Ziegler and colleagues studied 100 cases of KS in children under age 15. They reported that the incidence of childhood KS in Uganda in 1996 was 40 times as great as it was in the pre-AIDS era. DNA from HHV-8 was found in all cases of childhood KS tested. Distribution patterns of the tumors suggested the virus entered during birth or breast-feeding (Ziegler 1996).
But what about the correlational findings linking high use of alkyl nitrites to KS? When reviewing these findings, it’s important to bear in mind that correlation does not equal cause. An interesting case in point comes from a 1985 study by Haverkos et al. that is widely cited in support of the KS-alkyl nitrite connection. While the authors found a correlation between the high levels of nitrite use and KS, they also found many other statistically significant correlations. For instance, homosexual men with KS tend to have had hepatitis B; use drugs such as amphetamines, barbiturates, cocaine, LSD, and marijuana to name a few; had a greater number of sexual partners than those without KS; and have an income over $20,000 per year (Haverkos et al. 1985).
Not surprisingly, correlation is easily confused with fact. I’ve found that a semi-ridiculous analogy often helps bring the point home. For instance, while homosexual men with KS may also be more likely to own a three-legged dog than those without KS, there is no proven causal link between KS and three-legged dog ownership. It’s the same with alkyl nitrite use. Because we cannot prove the link is more than a correlation, the conclusions remain unclear. Often upon further analysis, as was the case with a reanalysis study done by Marmor et al. in 1982, when other variables are controlled for, nitrite use is shown to no longer be a significant factor.
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