Model-based evaluation of an infant HPV prophylactic vaccination program in Nigeria

Background: Nigeria introduced single-dose HPV vaccination for girls aged 9-14 in 2023, reaching approximately 60% aggregate coverage by 2025. While an important achievement, this remains short of the 90% coverage called for under the WHO's 90-70-90 cervical cancer elimination targets, and further scale-up depends on reaching out-of-school girls. In this study we used a model of HPV transmission in Nigeria to quantify the residual cervical cancer burden under continued adolescent delivery, assess how additional screening scale-up and equity assumptions modify it, and identify the effective coverage requirements for an infant HPV vaccination program to be non-inferior to the existing adolescent strategy. Methods: We used HPVsim, an agent-based microsimulation calibrated to Nigerian sexual behavior, HPV prevalence, and cervical cancer incidence, to project new cervical cancer cases and age-standardized incidence over 2025-2100 under scenarios which vary vaccination delivery mode (status-quo adolescent, WHO 90-70-90 adolescent scale-up, and 60/75/90% infant delivery), screening coverage (opportunistic 15% vs. scaled 70% aggregate), and the degree to which primary school completion correlated with vaccination (odds ratio 1 vs. 5) and with screening (odds ratio 1 vs. 3). Infant delivery scenarios were run at hypothetical effective-vaccine-efficacy-at-exposure values of 50%, 70%, and 95% - scenario inputs bracketing the plausible waning range, not evidence-based estimates of infant vaccine performance (no HPV vaccine trial has enrolled anyone below age 10). Each scenario was run at 50 replicates (10 calibration draws, 5 seeds); reported outcomes are the median across replicates and uncertainty ranges are interquartile (25th-75th percentile). Results: Continuation of Nigeria's current adolescent program is projected to avert 1.82 million cervical cancer cases (IQR 1.65-1.90 million; 95% UI 1.39-2.02 million) over 2025-2100 (a 53% reduction relative to no vaccination, IQR 51-55%; 95% UI 46-58%), with age-standardized incidence falling from 19.7 to 7.8 per 100,000 by 2100. However, 82% of the near-term (2025-2075) burden is projected to fall on the pre-2015 birth cohort, i.e. women already beyond the vaccination target age, leaving approximately 945,000 residual cases (IQR 905K-1.00M; 95% UI 835K-1.14M) in this cohort. Scaling up screening to WHO targets was estimated to avert a further ~387K cases (IQR 331-424K; 95% UI 269-515K), roughly 25% of the residual burden; results were about 6-8% better if the scale-up instead reached all women equitably regardless of education. Under a hypothetical scenario of infant vaccination at 90% coverage and 95% effective vaccine efficacy at exposure (matching adolescent-age performance), outcomes were comparable to full WHO adolescent scale-up (49% vs. 54% reduction in vaccine-targetable cohort cancers), but under a hypothetical 50% effective efficacy at Nigeria's DTP3-anchored 62% coverage the strategy averted only a fraction of these cancers. Conclusions: The near-term cervical cancer burden in Nigeria is dominated by cohorts vaccination cannot reach; scaling screening for them is the more consequential lever over the coming three decades and rests on established evidence. Findings on infant HPV delivery are exploratory and hypothesis-generating: they depend on three unverified empirical prerequisites - infant HPV vaccine immunogenicity in the first months of life, durability of protection across the ~15-25-year interval to peak HPV exposure, and coverage achievable through Nigeria's routine childhood immunization platform - and should not be read as a basis for any policy recommendation contingent on infant HPV delivery until those prerequisites are established.