Background:  Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide. Persistent high-risk HPV infection along with environmental and genetic factors predisposes individuals to cervical intraepithelial neoplasia (CIN) and subsequent progression to cancer. High expression levels of interleukin-10 (IL-10)—which could inhibit cytokines involved in the T_H1-T_H2 immunoregulation, down-regulate expression of MHC molecules, or induce the transcription of the early promoter of HPV—have been associated with the development of CIN and cervical cancer.

Methods:  We typed by polymerase chain reaction method using sequence-specific primers (PCR-SSP), 3 single nucleotide polymorphisms (SNP) in the promoter of IL10 gene and evaluated for their association with clearance of HPV infection in 226 African American adolescent females enrolled between 1996 and 2002 in the prospective Reaching for Excellence in Adolescent Care and Health (REACH) cohort. At enrollment and every 6 months thereafter, cervical lavage samples were tested for HPV using MY09/MY11/HMB01-based PCR and 32 HPV type-specific probes. For analytic purposes, HPV types were categorized according to phylogenetic patterns:  high-risk (16 and 18 plus all other types known to confer high-risk); 16-like (16 and 6 other types); 18-like (18 and 8 other types); and low-risk. Separately in HIV-1^– and 2 HIV-1⁺ groups (CD4⁺ >500 and CD4⁺ ≤500), Kaplan-Meier and Cox proportional hazards regression models were used to evaluate associations between IL10 SNP and time to HPV type-specific clearance.

Results:  Among HIV-1⁺ immunosuppressed individuals (CD4⁺ ≤500), the GCC haplotype in the IL10 promoter, which is known to with produce relatively high levels of IL-10, was associated with delayed clearance of high-risk HPV 16-like (RH = 0.46, 0.25 to 0.85, p = 0.01), 18-like (RH = 0.33, 0.16 to 0.67, p = 0.002), and any high-risk type (RH = 0.37, 0.20 to 0.68, p = 0.002), but not low-risk HPV types (RH = 0.60, 0.29 to 1.25, p = 0.17). No associations were observed among immunocompetent individuals.

Conclusions:  SNP in the IL10 promoter influence clearance of high-risk HPV types and warrants further studies of host genetic control of HPV pathogenesis and cervical cancer in the context of immunosuppression. This may also guide evaluations of HPV vaccine designs and treatments targeted at HIV-1⁺ individuals.