BACKGROUND: Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators and impact responses to standard immunizations. We conducted a cohort study to measure the influence of malaria and helminth infections on the immunogenicity of the bivalent HPV-16/18 vaccine. METHODS: We evaluated the association between malaria and helminth infections, and HPV-16/18 antibody responses among 298 Tanzanian females aged 10-25 years enrolled in a randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was diagnosed by examination of blood smears, and helminth infections were diagnosed by examination of urine and stool samples, respectively. Geometric mean antibody titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Parasitic infections were common; one-third (30.4%) of participants had a helminth infection and 10.2% had malaria parasitaemia. Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a reduction in HPV-16 or HPV-18 GMT at Month 7 or Month 12 follow-up visits among participants with helminths or malaria. There was some evidence that participants with malaria had increased GMTs compared to those without malaria. CONCLUSIONS: The data show high HPV immunogenicity regardless of the presence of malaria and helminth infections. The mechanism and significance for the increase in GMT in those with malaria is unknown.