BACKGROUND:WHO has recommended that one dose of human papillomavirus (HPV) vaccine can be given to individuals aged 9-20 years to prevent HPV infection. Estimating durability of immune responses after a single dose in the target age for vaccination is important. We report immunogenicity results in Tanzanian girls up to 5 years after receiving a dose. METHODS:In this open-label, randomised controlled trial (the Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls [DoRIS] trial), 930 Tanzanian schoolgirls aged 9-14 years were enrolled and randomly allocated to receive one, two, or three doses of either the two-valent vaccine (Cervarix; GSK, Wavre, Belgium) or nine-valent vaccine (Gardasil-9; Merck Sharp & Dohme, Haarlem, Netherlands). Seropositivity specific to HPV16 or HPV18, antibody geometric mean concentrations (GMCs), and antibody avidity were measured annually up to month 36. Participants in the one-dose and two-dose groups were followed annually in a long-term extension of the DoRIS trial to month 60; the primary outcome was seropositivity specific to HPV16 or HPV18 comparing one dose with two doses. FINDINGS:Single-dose seropositivity for HPV16 IgG antibodies at month 60 with either vaccine was more than 99% and non-inferior to two doses. 98% of girls in the one-dose two-valent vaccine group and 93% in the one-dose nine-valent group were seropositive for HPV18 at month 60; however, the non-inferiority criteria for HPV18 seropositivity comparing one dose with two doses were not met. Although HPV16 and HPV18 antibody GMCs after one dose were lower than those observed after two doses, antibody GMCs in the one-dose groups remained stable from month 12 to month 60. There was no evidence of a difference between the one-dose and two-dose groups in HPV16 or HPV18 antibody avidity at month 36 for either vaccine. INTERPRETATION:A single dose of HPV vaccine in girls aged 9-14 years continues to provide stable immune responses 5 years after vaccination, although ongoing surveillance for potential waning immunity after a single dose is needed. Participants are being followed up to 9 years after vaccination. FUNDING:UK Department of Health and Social Care, UK Foreign, Commonwealth & Development Office, Global Challenges Research Fund, UK Medical Research Council, and the Wellcome Trust through the Joint Global Health Trials Scheme; Bill & Melinda Gates Foundation.

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Objective: As part of the Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls (DoRIS; NCT02834637), the current study is one of the first to evaluate the financial and economic costs of the national rollout of an HPV vaccination program in school-aged girls in sub-Saharan Africa and the potential costs associated with a single dose HPV vaccine program, given recent evidence suggesting that a single dose may be as efficacious as a two-dose regimen.Methods: The World Health Organization's (WHO) Cervical Cancer Prevention and Control Costing (C4P) micro-costing tool was used to estimate the total financial and economic costs of the national vaccination program from the perspective of the Tanzanian government. Cost data were collected in 2019 via surveys, workshops, and interviews with local stakeholders for vaccines and injection supplies, microplanning, training, sensitization, service delivery, supervision, and cold chain. The cost per two-dose and one-dose fully immunized girl (FIG) was calculated.Results: The total financial and economic costs were US$10,117,455 and US$45,683,204, respectively, at a financial cost of $5.17 per two-dose FIG, and an economic cost of $23.34 per FIG. Vaccine and vaccine-related costs comprised the largest proportion of costs, followed by service delivery. In a one-dose sce-nario, the cost per FIG reduced to $2.51 (financial) and $12.18 (economic), with the largest reductions in vaccine and injection supply costs, and service delivery. Conclusions: The overall cost of Tanzania's HPV vaccination program was lower per vaccinee than costs estimated from previous demonstration projects in the region, especially in a single-dose scenario. Given the WHO Strategic Advisory Group of Experts on Immunization's recent recommendation to update dosing schedules to either one or two doses of the HPV vaccine, these data provide important baseline data for Tanzania and may serve as a guide for improving coverage going forward. The findings may also aid in the prioritization of funding for countries that have not yet added HPV vaccines to their routine immunizations.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

ABSTRACT The global burden of cervical cancer remains very high, with more than 340,000 potentially preventable deaths annually and disproportionally affects low-income and middle-income countries. Countries that have adopted HPV vaccination administer a multidose schedule with 2 doses offered to girls younger than 15 years, and 3 offered to girls 15 years and older or immunocompromised individuals. Unfortunately, several barriers to full immunization remain, and only 15% of girls in the target age group worldwide are estimated to be fully vaccinated. A single-dose vaccine would remove many barriers and be significantly cheaper; however, evidence is needed on the immunogenicity and efficacy. This randomized phase 3 clinical trial (DoRIS) aimed to examine immune responses after a single dose of HPV vaccine in the target age group for HPV vaccination in Tanzania. Girls aged 9–14 years who have not been vaccinated for HPV and did not have any history of cervical lesions, treatment for positive cervical cancer screening, or immunocompromised status were invited from Government schools to participate. Participants were randomized to 1 of 6 arms comprising 3 different dose schedules of 2 different HPV vaccines (3 doses over 6 months, 2 doses given 6 months apart, or a single dose for either the 2-valent vaccine or the 9-valent vaccine). Blood samples were collected for immunological assays at 1, 7, 12, and 24 months after vaccination. The primary study outcome was noninferiority of HPV 16 and HPV 18 specific seropositivity after a single dose compared with 2 or 3 doses of the same vaccine 24 months after vaccination. Primary analyses were undertaken in the per-protocol population, including those who received the allocated doses of HPV vaccine in the protocol-defined window. A sensitivity analysis included all participants who received at least 1 dose of HPV vaccine. A total of 930 girls were enrolled and randomized with 155 participants per group. At 24 months, 856 (93%) girls were included in the per-protocol analysis of anti-HPV 16 antibody responses, and 831 (91%) in the per-protocol analysis of anti-HPV 18. All but 2 participants were seropositive for HPV 16 IgG at 24 months (1 participant in each of the 1-dose arms was not), and all but 6 participants were HPV 18 seropositive at 24 months (2 in the 1-dose 2-valent group, 3 in the 1-dose 9-valent group, and 1 in the 3-dose 9-valent group). Noninferiority of HPV 16 seroconversion was met at 24 months for 1 dose compared with 2 doses or 3 doses for both vaccines; however, noninferiority for HPV 18 seroconversion was not met despite 98% of girls in the 1-dose arms of both vaccines testing positive for anti-HPV 18. There was no difference in serious adverse events among study groups or any serious adverse events related to the vaccine. The results of this study demonstrate that, in healthy Tanzanian girls, a single dose of the 2-valent or 9-valent HPV vaccines was well tolerated and resulted in high seropositivity and induced stable vaccine responses that persisted to 24 months.