Persistent infection with high-risk human papillomavirus (HPV) is a major risk factor for
cervical cancer, and HPV clearance seems to be under host genetic influence. This study evaluated associations between three single nucleotide polymorphisms in the
IL10 promoter and clearance of low- or high-risk
HPV infection in a cohort of 226 largely HIV-1-infected African-American adolescent females. Among immunosuppressed individuals (HIV-1 seropositive and CD4(+) </= 500), the GCC haplotype in the
IL10 promoter was associated with reduced clearance of high-risk HPV16-like [relative hazard (RH), 0.46; 95% confidence interval (95% CI), 0.25-0.85; P = 0.01], HPV18-like (RH, 0.33; 95% CI, 0.16-0.67; P = 0.002), and any high-risk type (RH, 0.37; 95% CI, 0.20-0.68; P = 0.002) but not with low-risk HPV type (RH, 0.60; 95% CI, 0.29-1.25; P = 0.17). No associations were observed among immunocompetent individuals. The
IL10 GCC haplotype has been associated with production of relatively high levels of
interleukin (IL)-10, which could (a) inhibit
cytokines such as
IL-2,
TNF-alpha,
IL-4,
IL-6, and
IL-12 that are involved in the T(H)1-T(H)2 immunoregulation; (b) down-regulate expression of MHC class I and class II molecules; or (c) induce the transcription of early promoter of HPV, all potentially contributing to duration of
HPV infection among immunosuppressed individuals. These results support the hypothesis that
IL10 polymorphisms influence the clearance of
infection with high-risk HPV types and warrant further studies of host genetic control of HPV pathogenesis and
cervical cancer in the context of immunosuppression.