Incident High-Grade Squamous Intraepithelial Lesions in Senegalese Women With and Without Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2

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Abstract
Background: Women infected with human immunodeficiency virus type 1 (HIV-1) and -2 may be at higher risk of developing cervical cancer than uninfected women. We assessed the relationships among human papillomavirus (HPV) types and persistence, HIV-1 and/or HIV-2 infection, and the development of high-grade cervical squamous intraepithelial lesions (HSILs) in a prospective study. Methods: We studied 627 women with and without HIV-1 and/or HIV-2 infection and high-risk HPV infection in Senegal, West Africa, who were assessed every 4 months for HSIL and HPV DNA over a mean follow-up of 2.2 years. Cox regression modeling was used to assess risks associated with development of HSIL. Results: During follow-up, 71 (11%) of 627 women developed HSIL as detected by cytology. HIV-infected women with high-risk HPV types were at greatest risk for development of HSIL. In multivariable modeling, infection with oncogenic HPV types—both persistent (hazard ratio [HR] = 47.1, 95% confidence interval [CI] = 16.3 to 136) and transient (HR = 14.0, 95% CI = 3.7 to 54)—was strongly associated with HSIL risk. In univariate analyses, HIV-positive women infected with HIV-2 were less likely to develop HSIL (HR = 0.3, 95% CI = 0.1 to 0.9) than HIV-positive women infected with HIV-1. HIV-positive women with CD4 + cell counts between 200 and 500 cells per microliter (HR = 2.2, 95% CI = 0.8 to 6.3) or fewer than 200 cells per milliliter (HR = 5.5, 95% CI = 2.0 to 15.2) were at greater risk of HSIL than HIV-positive women with CD4 counts of more than 500 cells per milliliter. High plasma HIV RNA levels were associated with increased HSIL risk (HR for each order of magnitude increase in the level of plasma HIV RNA = 1.4, 95% CI = 1.1 to 1.7; P = .005). After adjustment for HPV types and persistence, however, HIV type, plasma HIV RNA level, and CD4 count were no longer statistically significantly associated with increased risk of HSIL. Conclusions: HIV-1 and HIV-2 are associated with increased risk for development of HSIL. This risk appears to be associated primarily with increased HPV persistence that may result from immunosuppression related to HIV-1 and/or HIV-2 infection.

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