Results
The prevalence of CMV seropositivity correlates inversely to cancer incidence rates across a broad range of histology and worldwide (Table 3; the top 3 malignancies with strongest correlations are represented in Figs. 2-4 ). Correlations are obtained in 30/34 (88.2%) tumors and are highly significant over 25/34 (73.5%) histology types. Also, an inverse association attains a significance if annual incidence of new cancers of all histologic types was combined (Spearman’s ρ = -0.732; p< 0.001, Fig. 1 ). These results favor a possible oncoprotection that CMV infection provides to its host.
Conversely, CMV seroprevalence has a significant and co-incremental relation with an incidence of malignancies of nasopharynx and the gallbladder, suggesting a potential pro-oncogenic effect regarding these malignancies.
Notably, country-specific prevalence of CMV did not correlate inversely with an overall incidence of Kaposi’s sarcoma (Table 3 andFig. 5 , Spearman’s ρ = -0.007; p =0.953). This is in line with a requirement of an operative T cell-mediated oncolytic response as being critical for the expression a protective capacity of CMV, supporting a hypothesis of specific T cell viral oncoprevention. We propose that a severely disrupted T cell immunity in HIV/AIDS patients, who comprise a vast majority of population with Kaposi’s sarcoma, effectively precludes a CMV-associated anti-tumor response.
Table 1 exhibits comparative data on race/ethnic estimates of the incidence of all cancers combined (both genders, all anatomical sites, all ages) in the U.S, and the territorially matching prevalence of CMV seropositivity. The estimate of cancer incidence for Mexico is included as a contrasting population but was discarded from statistical calculations. The aggregated results of studies mentioned therein provide a clear representation of a higher CMV pervasiveness in the U.S. minorities than in non-Hispanic Whites.
Table 2 represents a statistical analysis of the SEER data on racial/ethnic rates of cancer (Henley et al. [44]) and the corresponding prevalence of CMV. Also pointed in Table 2 is a highly significant and inverse correlation (p <0.001; mean: -0.674; SD=0.018; CI=-0.711) between the standardized cancer incidence and the CMV seroprevalence in the U.S. An outlying group are the Eskimos (AI/AN), perhaps because of an impaired T cell function which distinguishes this ethnicity from the others [66,67]. Consequently, CMV-specific cytotoxic T cell oncolysis in Eskimos is not an efficient suppressor of clonogenic processes (see Discussion ). The results also support broad evidence (Figs. 1-4) suggesting a tendency of CMV seropositivity to monotonically decrease as SES improves across a range of developed and underdeveloped countries. This may explain a higher incidence of malignancies in economically progressive countries.