The statistical analysis revealed that homosexual sexual orientation (p = 0.04), syphilis reinfection (p = 0.01), and VDRL titers > 1:32 (p = 0.02) were correlated with atypical manifestations of syphilis; conversely, the variables of sex, age, stage of the disease, HIV seropositivity, TPHA titers, T. pallidum IgM antibodies, and coinfections by other bacterial sexually transmitted pathogens and by HR-HPVs were not statistically correlated with atypical syphilis manifestations (p > 0.05). The gene discussed is CD40LG; the disease is syphilis.