Evidence-based impact projections of single-dose human papillomavirus vaccination in India: a modelling study

Abstract

Background: Despite the high burden of cervical cancer, access to preventive measures remains low in India. A single-dose immunisation schedule could facilitate the scale-up of human papillomavirus (HPV) vaccination, contributing to global elimination of cervical cancer. We projected the effect of single-dose quadrivalent HPV vaccination in India in comparison with no vaccination or to a two-dose schedule.

Methods: In this modelling study, we adapted an HPV transmission model (EpiMetHeos) to Indian data on sexual behaviour (from the Demographic and Health Survey and the Indian National AIDS Control Organisation), HPV prevalence data (from two local surveys, from the states of Tamil Nadu and West Bengal), and cervical cancer incidence data (from Cancer Incidence in Five Continents for the period 2008-12 [volume XI], and the Indian National Centre for Disease Informatics and Research for the period 2012-16). Using the model, we projected the nationwide and state-specific effect of HPV vaccination on HPV prevalence and cervical cancer incidence, and lifetime risk of cervical cancer, for 100 years after the introduction of vaccination or in the first 50 vaccinated birth cohorts. Projections were derived under a two-dose vaccination scenario assuming life-long protection and under a single-dose vaccination scenario with protection duration assumptions derived from International Agency for Research on Cancer (IARC) India vaccine trial data, in combination with different vaccination coverages and catch-up vaccination age ranges. We used two thresholds to define cervical cancer elimination: an age-standardised incidence rate of less than 4 cases per 100 000 woman-years, and standardised lifetime risk of less than 250 cases per 100 000 women born.

Findings: Assuming vaccination in girls aged 10 years, with 90% coverage, and life-long protection by two-dose or single-dose schedule, HPV vaccination could reduce the prevalence of HPV16 and HPV18 infection by 97% (80% UI 96-99) in 50 years, and the lifetime risk of cervical cancer by 71-78% from 1067 cases per 100 000 women born under a no vaccination scenario to 311 (80% UI 284-339) cases per 100 000 women born in the short term and 233 (219-252) cases per 100 000 women born in the long term in vaccinated cohorts. Under this scenario, we projected that the age-standardised incidence rate threshold for elimination could be met across India (range across Indian states: 1·6 cases [80% UI 1·5-1·7] to 4·0 cases [3·8-4·4] per 100 000 woman-years), while the complementary threshold based on standardised lifetime risk was attainable in 17 (68%) of 25 states, but not nationwide (range across Indian states: 207 cases [80% UI 194-223] to 477 cases [447-514] per 100 000 women born). Under the considered assumptions of waning vaccine protection, single-dose vaccination was projected to have a 21-100% higher per-dose efficiency than two-dose vaccination. Single-dose vaccination with catch-up for girls and women aged 11-20 years was more impactful than two-dose vaccination without catch-up, with reduction of 39-65% versus 38% in lifetime risk of cervical cancer across the ten catch-up birth cohorts and the first ten routine vaccination birth cohorts.

Interpretation: Our evidence-based projections suggest that scaling up cervical cancer prevention through single-dose HPV vaccination could substantially reduce cervical cancer burden in India.

Funding: The Bill & Melinda Gates Foundation.

Figure 1

Estimated HPV prevalence over time in girls and women aged 15–40 years (A, C, E) and cumulative risk of HPV infection up to age 40 years, by birth cohort (B, D, F) (A, B) Base-case scenario, with routine vaccination in girls aged 10 years with 90% coverage and life-long vaccine protection by either single-dose or two-dose schedule, without catch-up vaccination. (C, D) Scenario with routine vaccination in girls aged 10 years with 90% coverage and without catch-up vaccination (as in the base-case scenario) but under vaccine protection assumption D for single-dose vaccination. (E, F) Scenario with routine vaccination in girls aged 10 years with 90% coverage and life-long protection, under assumption A for single-dose vaccination (as in the base-case scenario), but with catch-up vaccination in individuals aged up to 20 years that has 60% coverage. (A, C, E) HPV prevalence in girls and women aged 15–40 years over a 50 year time horizon. (B, D, F) Estimated cumulative risk of HPV infection is shown for 5-year birth cohorts; each bar shows 80% uncertainty interval and their weighted mean according to the contribution of each HPV type to the total cervical cancer burden to approximate the relative reduction in lifetime risk of cervical cancer (purple line); the dash vertical line shows the start of the vaccination programme. HPV=human papillomavirus.

Figure 2

Projected mean lifetime risk of cervical cancer before (A) and after (B) start of vaccination, under the base-case scenario, by state in India Lifetime risk of cervical cancer in cases per 100 000 women born in the base-case scenario (ie, routine vaccination in girls aged 10 years with 90% coverage under life-long vaccine protection by either single-dose and two-dose schedule and without catch-up vaccination). (A) Baseline risk without vaccination. (B) Projections for the 5-year birth cohort vaccinated 46–50 years after the start of the vaccination programme; elimination of cervical cancer based on ASIR only is based on the WHO elimination threshold 4 cases per 100 000 woman-years, whereas elimination based on ASIR and SLTR also incorporates the threshold for SLTR of 250 cases per 100 000 women born. Exact projected values of lifetime risk, SLTR, and ASIR are shown in the appendix (p 39). ASIR=age-standardised incidence rate. SLTR=standardised lifetime risk.

Figure 3

Estimated cervical cancer risk by vaccine protection assumption and coverage Estimates are based on reduction of cervical cancer risk in the long term (ie, the 5-year birth cohort vaccinated 46–50 years after the start of the vaccination programme).(A) Percentage relative reduction in lifetime risk of cervical cancer. (B) Relative efficiency in the number of cervical cancer cases prevented per dose under single-dose versus two-dose vaccination. (C) ASIR rate of cervical cancer; cells with a thick outline indicate that the ASIR projections are below the WHO cervical cancer elimination threshold of 4 cases per 100 000 woman-years; baseline ASIR without vaccination being 11 cases per 100 000 woman-years. (D) Standardised lifetime risk of cervical cancer; none of the cells are below the elimination threshold of 250 cases per 100 000 women born; baseline standardised lifetime risk without vaccination being 1339 cases per 100 000 women born. The setting across all scenarios is routine vaccination in girls aged 10 years without catch-up vaccination. ASIR=age-standardised incidence rate. *Base-case scenario.

Figure 4

Estimated relative reduction in lifetime risk of cervical cancer with catch-up vaccination, by age group at start of vaccination programme Relative reduction in lifetime risk of cervical cancer in girls and women aged 11–30 years across all states in India at the start of vaccination, unstratified (A) and stratified by age at the start of the vaccination programme (B). Base-case scenario is 90% coverage in routine vaccination cohort of girls aged 10 years, with life-long vaccine protection, without any catch-up. All other scenarios are the same scenario with increasing maximum age of catch-up up to age 15, 20, 25, and 30 years. 80% uncertainty intervals are reported in the appendix (p 52).