Objectives In this study, we determined the incidence and persistence of human papillomavirus ( HPV ) strains and of squamous intraepithelial lesions ( SIL ) or worse cytology in 237 HIV ‐positive and HIV ‐negative Rwandan women and whether the interleukin ( IL )‐28B single nucleotide polymorphism ( SNP ) at rs12979860 correlated with susceptibility to and persistence of HPV infection. Methods Cervical samples were collected at baseline and after 9, 18 and 24 months for a 40‐ HPV DNA screening test and a ThinPrep Pap test. Genotyping of the IL ‐28B SNP rs12979860 was performed using real‐time polymerase chain reaction ( PCR ). Results Chronic high‐risk ( HR ) HPV infections occurred in 56% of HIV ‐positive women, while no HIV ‐negative women developed HPV chronicity. High‐grade SIL ( HSIL ) or cancer was diagnosed in 38% of HIV ‐positive women with persistent HR ‐ HPV infections. HIV and HR ‐ HPV positivity at baseline were factors associated with an increased risk of HPV persistence. Additionally, HR ‐ HPV positivity at baseline was associated with an increased risk of developing HSIL or worse cytology. The unfavourable T/x genotype at rs12979860 is common among Africans, and women with this genotype were found to be more commonly infected with HPV . Conclusions HPV screening in Rwanda may help to identify women at risk of developing cervical cancer and polymorphism in IL ‐28B may be associated with risk of contracting HPV infection.