Comparison of HPV vaccination strategies for pilot implementation in North India

INTRODUCTION

Cervical cancer remains a significant public health challenge in India, accounting for an estimated 127,526 new cases and 79,906 deaths in 2022.¹ This burden persists despite cervical cancer being a disease with both primary (vaccination) and secondary (screening) prevention potential. The World Health Organization (WHO) has set an ambitious 90-70-90 target for global elimination of cervical cancer, including 90% Human Papilloma Virus (HPV) vaccination coverage for girls by age 15.²

India’s interim budget announcement in 2024 marked a pivotal policy opportunity to address this gap by encouraging state-led HPV vaccination for girls aged 9-14 years.³ As individual Indian states prepare for pilot implementation using school-based platforms, decision-makers face a critical choice between competing vaccination strategies. The core dilemma involves balancing emerging evidence supporting a single-dose HPV vaccination schedule for an established vaccine (Gardasil) against the National priority of implementing an indigenous vaccine (Cervavac), while accounting for cost-effectiveness and the programmatic challenges associated with multi-dose vaccination. This paper therefore compares three strategies for school-based HPV vaccination pilot planned in a Constituency in a North Indian state, aiming to inform an evidence-based and operationally sound policy decision for cervical cancer prevention in India.

METHODS

Study design, setting and period

This was a comparative programmatic and cost analysis undertaken to inform planning for an HPV vaccination pilot in a Constituency in a North Indian state. The target population for the pilot planning comprised an estimated 6,300 girls aged 9-14 years, including approximately 6,000 school-going girls across 169 schools and 300 out-of-school girls. The planning and the comparative analyses were undertaken between July to August, 2025.

Vaccination strategies compared

Three strategies were compared.

Strategy 1

Single-dose Gardasil (quadrivalent HPV vaccine; Merck Sharp & Dohme LLC, US).

Strategy 2

Two-dose Cervavac (quadrivalent HPV vaccine; Serum Institute of India), administered at 0 and 6 months.

Strategy 3

Single-dose Cervavac (quadrivalent HPV vaccine; Serum Institute of India).

Data sources and comparison parameters

The analysis used operational data, resource mapping, microplanning details, and cost component assumptions derived from official sources. This was supplemented by recommendations from WHO Strategic Advisory Group of Experts on Immunization (SAGE) , India’s National Technical Advisory Group on Immunization (NTAGI), WHO position paper on HPV vaccines, and the national Operational Guidelines for HPV vaccine introduction, along with evidence from single-dose efficacy trials, Cervavac licensure trial data, and cost effectiveness modelling studies in the Indian context.^4-7 Key comparison parameters included programmatic feasibility, programmatic cost, and the strength of supporting evidence. The programmatic costs, including logistics, human resource, operational cost and, vaccine procurement prices were estimated based on stakeholder consultations and prevailing market information for pilot programme procurement (approximately Rs. 3,400 per dose for Gardasil and Rs. 1,700 per dose for Cervavac). Ethical approval was not required, as the analysis was based on publicly available guidelines, operational planning documents, and published literature.

RESULTS

The three strategies presented a distinct trade-off with respect to the programmatic requirements, financial cost, and the strength of the supporting evidence, as summarized in Table 1.

Programmatic requirements

Strategy 1 (single-dose Gardasil) requires only a single school visit per vaccination cohort, giving it the lowest programmatic burden of the three options, despite having the highest per-dose vaccine procurement cost. Strategy 2 (two-dose Cervavac) is administered at 0 and 6 months and therefore requires two school visits per cohort. Although its per-dose procurement cost was lower than Gardasil’s, this strategy required greater cold-chain capacity and carried the highest overall logistics and human-resource burden of the three options. The Strategy 3 (single-dose Cervavac) shares strategy 1's similar programmatic burden as strategy 1 due to single school visit, and at the lower per-dose price of Cervavac.

Comparative programmatic and financial costs

Comparative estimates of programmatic and financial costs of the three strategies are presented in table 2. Strategy 1 incurred the highest vaccine procurement cost but lower logistics and human resource (HR) expenditure. Strategy 2 required double the number of vaccine doses, resulting in higher logistics and HR expenditure, including a 64% higher total HR requirement than Strategy 1 or Strategy 3 (2,120 vs. 1,288 man-hours). Strategy 3 had the lowest total estimated cost of the three strategies, but currently lacks supporting evidences for programmatic adoption.

*Full itemized cost and human-resource breakdown in Table 2.

DISCUSSION

The comparative findings above must be interpreted against the existing evidence base and current national policy. Strategy 1 (single-dose Gardasil) is supported by the strongest available evidence, including a 10 years follow-up data from India showing approximately 95% efficacy (95% CI: 85.0–99.9) against persistent HPV 16/18 infection with a single dose, comparable to two- and three-dose regimens.⁸ This finding are in line with the 2022 WHO SAGE recommendation for an alternative single-dose schedule and has been shown to be highly cost-effective in Indian modelling studies.^4,9 But, this strategy have a higher per-dose procurement cost and this also relies on non-indigenous vaccine product. This must be weighed against national policy priorities favouring indigenous vaccine manufacture.³

Strategy 2 (two-dose Cervavac) uses an indigenously developed vaccine and aligns with the current NTAGI recommendation for introduction of an HPV vaccine into the Universal Immunization Programme. The efficacy of this strategy is also based on a two-dose non-inferiority trial.^5,10 However, two-dose schedules might increase the risk of dropout between doses, which can reduce overall effectiveness and increase the cost per fully immunized girl. This also inflates the programmatic and cold-chain burden than single-dose schedules.¹¹ A statewide two-dose HPV vaccination campaign in Sikkim achieved over 95% second-dose coverage, demonstrating that high two-dose coverage is achievable within the Indian programmatic context.¹² However, replicating this outcome in a new pilot setting would, require a similarly high level of intersectoral coordination, sustained follow-up, and political and administrative commitment.

Strategy 3 (single-dose Cervavac) represents an emerging rather than a policy-ready option for HPV vaccination piloting. As discussed, the two-dose schedule of Cervavac has established non-inferiority to Gardasil.¹⁰ But, WHO’s single-dose recommendation for HPV vaccination does not automatically extend to newly licensed vaccines in the absence of product-specific data.^4,6 The Indian council of medical research (ICMR) is currently conducting an immune-bridging study comparing single-dose Cervavac with single-dose Gardasil, with results expected in 2027.¹³ Programmatic adoption of single-dose Cervavac would be premature until this evidence becomes available, even though it offers the lowest theoretical cost and would avoid the logistical burden of multi-dose delivery.

Taking all these considerations, highlight a substantive trade-off for the pilot between Strategy 1 and Strategy 2, reflecting a broader tension between adopting the schedule with the strongest global efficacy evidence versus adhering to the national product recommendation for an indigenously manufactured vaccine. This analysis has certain limitations. It relies on cost estimates derived from operational planning documents and standard programmatic assumptions rather than actual expenditure data, and it does not model long-term programmatic impact or potential waning of vaccine-induced immunity. The findings reflect a specific pilot context in North India and may not be directly generalizable to other states or settings with different school-enrolment patterns, cold-chain infrastructure, or health-workforce availability.

CONCLUSION

Within the context of a pilot in Indian setting, Strategy 1 (single-dose Gardasil) appears to be the most evidence-based and operationally efficient choice for initial implementation in the constituency. This approach maximizes the likelihood of achieving high, equitable vaccination coverage with minimal operational burden. However, acknowledging the national importance of Cervavac and its potential long-term cost advantages, the single-dose Cervavac strategy and the associated policy decision may be revisited as further evidence becomes available from the ongoing ICMR trial.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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