The India IARC trial evaluated HPV vaccination regimens among 20,000 girls aged 10–18. Initially designed to compare two- versus three-dose schedules, program suspension led to observational analysis of one-, two-, and three-dose cohorts. Over 10 years, single-dose recipients demonstrated robust, sustained immune responses against HPV 16/18, with stable antibody levels and comparable efficacy to multi-dose schedules in preventing persistent infections and CIN2+. Attack rates for non-vaccine HPV types were similar across groups, indicating comparable exposure. Findings strongly support one-dose vaccination as an effective, resource-efficient strategy for LMICs.