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Cited by 45Cervical Cancer and HPV ResearchWomen's cancer prevention and managementGenital Health and Disease

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

Open access
Man, Irene, Georges, Damien, de Carvalho, Tiago M, Ray Saraswati, Lopamudra, Bhandari, Prince, Kataria, Ishu, Siddiqui, Mariam, Muwonge, Richard +6 more·2022·The Lancet Oncology
DOI 10.1016/s1470-2045(22)00543-5PMC PMC9622421
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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.

AI snapshot

Written from the paper’s full text.

TL;DR

In a modelling study adapted to Indian data, single-dose quadrivalent HPV vaccination in girls aged 10 years with 90% coverage and life-long protection was projected to reduce HPV16/18 prevalence by 97% by 50 years and lifetime cervical cancer risk by 71–78% in vaccinated cohorts. Single-dose vaccination was projected to be 21–100% more efficient per dose than two-dose vaccination and could meet the WHO ASIR elimination threshold nationwide, though the stricter standardised lifetime risk threshold was met in only 17 of 25 states.

Key findings

  • In the base-case scenario (routine vaccination in girls aged 10 years, 90% coverage, life-long protection), HPV16/18 prevalence among women aged 15–40 years was projected to fall by 63% at 20 years and by 97% (80% UI 96–99) at 50 years; lifetime cervical cancer risk fell by 71% in the short term and 78% in the long term, from 1067 cases per 100 000 women born with no vaccination to 311 (80% UI 284–339) and 233 (219–252) cases per 100 000 women born, respectively.
  • The WHO ASIR elimination threshold (<4 cases per 100 000 woman-years) was projected to be met nationwide in the long term, with state-level ASIRs ranging from 1·6 (80% UI 1·5–1·7) to 4·0 (3·8–4·4) per 100 000 woman-years; the complementary SLTR threshold (<250 cases per 100 000 women born) was met in 17 (68%) of 25 states but not nationwide, with state-level SLTRs ranging from 207 (194–223) to 477 (447–514) per 100 000 women born.
  • Single-dose vaccination was projected to have 21–100% higher per-dose efficiency than two-dose vaccination under the considered waning-protection assumptions; single-dose vaccination with catch-up for ages 11–20 years reduced lifetime cervical cancer risk by 39–65% versus 38% for two-dose vaccination without catch-up across the ten catch-up birth cohorts and the first ten routine vaccination birth cohorts.
  • The discussion states that HPV vaccination could prevent close to 1 million cases of cervical cancer in the lifetime of the 120 million Indian girls currently aged 10 years and younger.

Methods

  • Modelling study using EpiMetHeos, an agent-based dynamic HPV transmission model implemented as an extension of EpiModel (version 2.0.3); the model population (n=20 000) was stratified by age, sex, and sexual activity risk group, and transmission of 13 high-risk HPV types was modelled independently.
  • Calibrated to Indian data: sexual behaviour from the Demographic and Health Survey and the Indian National AIDS Control Organisation; HPV prevalence from surveys in Tamil Nadu and West Bengal; cervical cancer incidence from Cancer Incidence in Five Continents volume XI (2008–12) and the Indian National Centre for Disease Informatics and Research (2012–16). States were clustered by cervical cancer incidence, and projections for Tamil Nadu and West Bengal were extrapolated to other states within each cluster.
  • Projected nationwide and state-specific HPV prevalence and cervical cancer outcomes over 100 years or in the first 50 vaccinated birth cohorts, using the 100 best-fitting parameter sets and 80% uncertainty intervals. Scenarios included no vaccination, single-dose and two-dose vaccination, 60–100% coverage, catch-up vaccination to ages 15, 20, 25, or 30 years, and single-dose protection assumptions A–E; no cervical cancer screening was assumed.

Limitations

  • The paper states that baseline cervical cancer risk (11 cases per 100 000 woman-years) is lower than the GLOBOCAN estimate (18·0 cases per 100 000 woman-years) because low-incidence Indian states not in CI5 were included; using GLOBOCAN estimates would make reaching the WHO elimination threshold more difficult, though it should still be possible under high vaccine coverage and efficacy.
  • The paper states that the relative effect of HPV vaccination on cervical cancer risk was approximated by the relative effect on cumulative high-risk HPV infection up to age 40 years; truncation at this age was motivated by the reduced likelihood of infections acquired after age 40 progressing to cancer and the shorter time to develop cervical cancer in older age groups.
  • The paper states that results are subject to uncertainty about changes in sexual behaviour over time, and that changing sexual behaviours related to an emerging economy might make cervical cancer control more challenging than projected. Evident from the methods: the model assumed no cervical cancer screening and constant vaccination coverage throughout the simulated 100-year time frame.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/s1470-2045(22)00543-5

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

22 of 38 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    In India, access to preventive measures for cervical cancer, including HPV vaccination and cervical cancer screening, remains low.

    “Despite the high burden of cervical cancer, access to preventive measures remains low in India.”
    • Also stated in: § Introduction · plain
      “Nevertheless, in India, there is still little access to HPV vaccination and cervical cancer screening.8, 9”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [8] Bruni, 2022, Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis, Lancet Glob Health source

      The Discussion (page unavailable) reports that fewer than 3% of women aged 30–49 in India had ever been screened in a 2017–18 survey, supporting low access to cervical cancer screening. The paper does not establish that access to HPV vaccination in India is also low, so it supports only part of the attributed claim. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [9] Sankaranarayanan, 2019, Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts, Lancet Oncol source
  • Premisecitation

    Access to cervical cancer screening in India is very low.

    “Because access to cervical cancer screening in India is very low, we assumed no screening throughout all scenarios.8”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Bruni, 2022, Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis, Lancet Glob Health source
  • Premisecitation

    Initial results from a vaccine trial in Kenya designed to compare the protection of single-dose versus multi-dose HPV vaccination corroborate the findings on single-dose HPV vaccination.

    “Recently, initial results from a vaccine trial in Kenya12 designed to compare the protection of single-dose versus multi-dose HPV vaccination corroborate these findings.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [12] Barnabas, 2022, Efficacy of single-dose human papillomavirus vaccination among young African women, NEJM Evid source

      The Discussion reports that the Kenyan trial’s initial 18-month results showed high protection from single-dose HPV vaccination, building on earlier observational findings. But the Methods (Trial design and Oversight) state that the trial compared single-dose HPV vaccines with meningococcal vaccination, not with multidose HPV vaccination; similarity to multidose regimens was a conclusion, not a direct trial comparison. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Findingown data

    In a separate health economics analysis, single-dose HPV vaccination with catch-up in girls aged 11-20 years was found to be cost-effective under the WHO recommended threshold of one-times GDP per capita.

    “In a separate health economics analysis (unpublished), we found that single-dose HPV vaccination with catch-up vaccination in girls aged 11–20 years could be cost-effective under the WHO recommended cost-effectiveness threshold of one-times gross domestic product per capita.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [30] Marseille, 2015, Thresholds for the cost-effectiveness of interventions: alternative approaches, Bull World Health Organ source
  • Premisecitation

    Higher valency vaccines are likely to be efficacious under a single-dose schedule.

    “higher valency vaccines, which are also likely to be efficacious under a single-dose schedule.12”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] Barnabas, 2022, Efficacy of single-dose human papillomavirus vaccination among young African women, NEJM Evid source
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 25

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HPV vaccines have demonstrated high efficacy for three-dose and two-dose schedules.

    “The licensed prophylactic human papillomavirus (HPV) vaccines protect against infection with vaccine-targeted HPV types, precancerous lesions, and invasive cervical cancer, have demonstrated high efficacy for three-dose and two-dose schedules,3, 4 and have consistently been shown to be safe.5”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Lei, 2020, HPV vaccination and the risk of invasive cervical cancer, N Engl J Med source

      The HPV Vaccination section (page not provided) says Sweden used a three-dose schedule from 2006 and a two-dose schedule for school-based programs from 2015. The Discussion reports established HPV vaccine efficacy, but this study classified anyone receiving at least one dose as vaccinated and did not report efficacy separately for the two schedules. It therefore does not establish high efficacy for each schedule. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [4] Falcaro, 2021, The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study, Lancet source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HPV vaccines have consistently been shown to be safe.

    “The licensed prophylactic human papillomavirus (HPV) vaccines protect against infection with vaccine-targeted HPV types, precancerous lesions, and invasive cervical cancer, have demonstrated high efficacy for three-dose and two-dose schedules,3, 4 and have consistently been shown to be safe.5”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [5] Arbyn, 2018, Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors, Cochrane Database Syst Rev source

      The Description of the intervention (page unavailable) says L1 virus-like-particle HPV vaccines were well tolerated in phase I trials. That supports a limited safety finding, but the copy does not establish that licensed HPV vaccines have consistently been shown to be safe across studies or settings. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Cervical cancer could be eliminated as a public health problem with appropriate preventive measures.

    “Yet, cervical cancer could be eliminated as a public health problem with appropriate preventive measures.2”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [2] Brisson, 2020, Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries, Lancet source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    This study adheres to HPV-FRAME, a quality framework for modelled evaluations of HPV-related cancer control.

    “This study adheres to HPV-FRAME, a quality framework for modelled evaluations of HPV-related cancer control (appendix pp 29–31).16”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] Canfell, 2019, HPV-FRAME: a consensus statement and quality framework for modelled evaluations of HPV-related cancer control, Papillomavirus Res source

  • May combine two claims.

    Study design and conductreasoning

    EpiMetHeos was calibrated to Tamil Nadu to represent states in the high cervical cancer incidence cluster and to West Bengal to represent states in the low cervical cancer incidence cluster.

    “we calibrated EpiMetHeos to the state of Tamil Nadu to represent the states in the high cancer incidence cluster, and the state of West Bengal to represent the states in the low cancer incidence cluster”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [19] Franceschi, 2005, Papillomavirus infection in rural women in southern India, Br J Cancer source

      Materials and Methods identifies the study site as Dindigul District, Tamil Nadu, and the Discussion compares its HPV prevalence with that in high-risk cervical-cancer areas. The Discussion also mentions a West Bengal HPV survey, but does not classify West Bengal as a low-incidence state or establish high- and low-incidence state clusters. The EpiMetHeos calibration is the citing authors’ own action, not a finding of this source. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [20] Dutta, 2012, Prevalence of human papillomavirus in women without cervical cancer: a population-based study in Eastern India, Int J Gynecol Pathol source
    • cites [21]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Among 2005-14 birth cohorts worldwide, the largest burden of cervical cancer is projected in low-income and middle-income countries, with close to a sixth of cases projected to be in India, making it the country with the highest expected burden.

    “Among 2005–14 birth cohorts worldwide, the largest burden of cervical cancer is projected in low-income and middle-income countries, with close to a sixth of cases projected to be in India, making it the country with the highest expected burden.7”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] Bonjour, 2021, Global estimates of expected and preventable cervical cancers among girls born between 2005 and 2014: a birth cohort analysis, Lancet Public Health source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The finding that single-dose HPV vaccination with catch-up is cost-effective is consistent with a previous multi-country modelling study in low-income and middle-income settings including India.

    “This finding is consistent with a previous multi-country modelling study on low-income and middle-income settings, including India.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [31] Drolet, 2021, Optimal human papillomavirus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources: a mathematical modelling analysis, Lancet Infect Dis source

      The Methods (Study design and countries; page unavailable) identify a four-country modelling study that includes India. The Results (page unavailable) say one-dose vaccination of girls aged 9–14 years was cost-effective compared with no vaccination, but the explicitly described catch-up strategy used a five-year interval between two doses. The paper does not directly establish that a single-dose programme with catch-up is cost-effective without qualifications about one-dose protection. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Single-dose HPV vaccination provides comparable or non-inferior efficacy against persistent HPV infection compared with multi-dose schedules, with lower but sustained antibody levels for at least 11 years after vaccination.

    “Notably, the IARC India trial with a quadrivalent vaccine, and the Costa Rica Trial with a bivalent vaccine, have shown comparable efficacy between single-dose and multi-dose schedules, with sustained antibody levels for at least 11 years after vaccination.”
    • Also stated in: § Introduction · plain
      “Vaccine trials have shown that a single-dose schedule provides non-inferior efficacy against persistent HPV infection compared with multi-dose schedules, with lower, but sustained, antibody levels up to at least 11 years after vaccination.10, 11”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [10] Whitworth, 2020, Efficacy and immunogenicity of a single dose of human papillomavirus vaccine compared to no vaccination or standard three and two-dose vaccination regimens: a systematic review of evidence from clinical trials, Vaccine source

      The Discussion reports no difference in HPV16/18 infection incidence or persistence between one-, two-, and three-dose recipients through year four or seven, and says single-dose antibody levels were lower but remained relatively stable during follow-up. The Conclusions limit the reported follow-up to seven years; our copy does not support sustained antibody levels for at least 11 years. Page numbers were not available in the indexed passages. (LLM, conf=0.91)

      Experimental — accuracy not yet measured
    • cites [11] Basu, 2021, Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study, Lancet Oncol source

      The Discussion reports that one dose of the quadrivalent vaccine had efficacy against persistent HPV 16/18 infection no different from two or three doses through 10 years. It also says single-dose antibody concentrations remained sustained for at least a decade, but does not establish the claimed 11-year duration or that those levels were lower than after multiple doses. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Truncation at age 40 years was motivated by the reduced likelihood of infections acquired beyond this age progressing to cancer due to postmenopausal hormonal patterns and shorter time to develop cervical cancer in older age.

    “truncation at this age was motivated by the reduced likelihood of infections acquired beyond this age to progress to cancer due to the hormonal patterns after menopause, and the shorter time to develop cervical cancer in this older age group.34, 35”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [34] Schiffman, 2016, Carcinogenic human papillomavirus infection, Nat Rev Dis Primers source
    • cites [35] Plummer, 2012, Time since first sexual intercourse and the risk of cervical cancer, Int J Cancer source

      The Discussion links lower cancer risk from HPV infections acquired at older ages to menopausal changes. However, Materials and Methods specifies truncation at age 45, not 40, and the cited passages do not give a shorter time to develop cancer as a reason for truncation. Page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    Our projections support previous modelling studies that found high coverage HPV16/18 vaccination in girls aged 10 years could considerably reduce cervical cancer burden in India and enable reaching the WHO elimination target even with single-dose vaccination.

    “Our projections also support previous modelling studies2, 31, 32 that found high coverage of vaccination against HPV16 and HPV18 in girls aged 10 years could reduce the burden of cervical cancer in India considerably, and enable the country to reach the WHO elimination target even with single-dose vaccination.”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [2] Brisson, 2020, Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries, Lancet source

      The Abstract Methods and Findings support the broad prediction that high-coverage girls-only HPV vaccination could substantially reduce cervical cancer incidence, and the Results say an HPV16/18-only vaccine might permit elimination in some LMICs. But the model’s base case vaccinated girls at age 9 with catch-up through age 14 and assumed lifetime protection; our copy does not establish the claimed India-specific elimination result with single-dose vaccination. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [31] Drolet, 2021, Optimal human papillomavirus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources: a mathematical modelling analysis, Lancet Infect Dis source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [32] Diaz, 2008, Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India, Br J Cancer source

      The Results report a 44% reduction in cervical cancer incidence with pre-adolescent vaccination in India, supporting the claim of a considerable reduction. The Strategies section specifies vaccination before age 12 and a three-dose base case, not specifically age 10 or a single dose. The paper does not assess whether vaccination could meet the WHO elimination target. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    Using GLOBOCAN baseline estimates would make reaching the WHO elimination threshold more difficult but still possible under high vaccine coverage and efficacy.

    “Using GLOBOCAN estimates would make reaching the WHO elimination threshold more difficult, but should still be possible under high vaccine coverage and efficacy.2, 31”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [2] Brisson, 2020, Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries, Lancet source

      The Discussion (page not provided) says the models used GLOBOCAN incidence estimates and that underreporting could mean elimination takes longer than predicted. It does not say that using GLOBOCAN estimates itself makes elimination harder. It also says high-burden countries need screening in addition to high vaccination coverage to reach the WHO threshold; vaccine coverage and efficacy alone are not sufficient across all countries. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [31] Drolet, 2021, Optimal human papillomavirus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources: a mathematical modelling analysis, Lancet Infect Dis source

      The Methods (Analysis; page unavailable) say the model predictions were fitted to GLOBOCAN 2020 cervical-cancer incidence estimates, and the Findings report that vaccination could achieve elimination in Vietnam, India, and Nigeria, but not Uganda. The paper does not establish the claimed comparison that using GLOBOCAN estimates would make elimination more difficult, or show that high vaccine coverage and efficacy would make it possible across settings; its Discussion says countries with incidence like Uganda’s would likely also need screening. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    When using the higher nationwide baseline estimate from GLOBOCAN, attainment of the ASIR elimination threshold is more difficult but still possible.

    “When using the higher nationwide estimate reported on GLOBOCAN, attainment of the elimination threshold is more difficult but still possible”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The single-dose strategy with catch-up was estimated to reach 80% higher per-dose efficiency than two-dose vaccination under 60% coverage and 71% higher under 90% coverage.

    “the single-dose strategy was estimated to reach 80% higher per-dose efficiency than two-dose vaccination under 60% coverage and 71% higher per-dose efficiency under 90% coverage”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Catch-up vaccination in girls aged 11-15 years with 60% coverage was projected to reduce their lifetime risk by 53% (80% UI 50-57), whereas the same catch-up in women aged 26-30 years was estimated to reduce lifetime risk by only 14% (12-16).

    “catch-up vaccination in girls aged 11–15 years with 60% coverage could reduce their lifetime risk by 53% (80% UI 50–57), whereas the same catch-up in women aged 26–30 years is estimated to reduce lifetime risk by only 14% (12–16”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Under the same scenario, HPV vaccination could reduce 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.

    “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.”
    • Also stated in: § Introduction · hedged
      “We found that single-dose vaccination with long-lasting protection and 90% coverage would prevent up to 78% of cases of cervical cancer among vaccinated birth cohorts across the country”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Under life-long vaccine protection assumption A, the single-dose strategy with catch-up increased the reduction in lifetime risk to an estimated 57% (56-58) under 60% catch-up coverage and 65% (64-66) under 90% catch-up coverage.

    “under life-long vaccine protection assumption A, the single-dose strategy with catch-up increased the reduction in lifetime risk to an estimated 57% (56–58) under 60% catch-up coverage, and 65% (64–66) under 90% catch-up coverage”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Under this scenario, 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).

    “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).”
    • Also stated in: § Introduction · plain
      “whereas the threshold proposed on the basis of standardised lifetime risk (250 cases per 100 000 women born) was projected to only be achieved in 17 (68%) of 25 Indian states”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the base-case scenario, the WHO cervical cancer elimination threshold (ASIR <4 cases per 100 000 woman-years) could be attained in low-incidence Indian states in the short term and across all states in the long term, with projected ASIRs of 1.6-4.0 cases per 100 000 woman-years.

    “As a result of the projected reduction in cervical cancer risk, the WHO elimination threshold could already be attained in the low cancer incidence states in the short term and across all states in the long term, with ASIRs ranging between 1·6 cases (80% UI 1·5–1·7) and 4·0 cases (3·8–4·4) per 100 000 woman-years”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Under base-case single-dose vaccination, the SLTR threshold of 250 cases per 100 000 women born was projected to be attained in the long term in only 17 (68%) of 25 Indian states, not nationwide, with projected SLTRs of 207-477 cases per 100 000 women born across states.

    “As for SLTR, the threshold of 250 cases per 100 000 women born was projected to be attained in the long term only in 17 (68%) of 25 Indian states, but not nationwide, with SLTRs ranging between 207 cases (80% UI 194–223) and 477 cases (447–514) per 100 000 women born across states”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among women aged 11-30 years at the start of the vaccination programme, the nationwide lifetime risk of cervical cancer was projected to be reduced by 3% (80% UI 2-4), with the highest reduction of 7% (5-10) in the youngest age group, 11-15 years.

    “Among women aged 11–30 years at the start of the vaccination programme, we projected that the nationwide lifetime risk of cervical cancer would be reduced by 3% (80 UI 2–4; figure 4A), with the highest reduction of 7% (5–10) being in the youngest age group, 11–15 years”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The nationwide baseline cervical cancer risk reported here (11 cases per 100 000 woman-years) is lower than the GLOBOCAN estimate (18.0 cases per 100 000 woman-years) because the study included data from low-incidence Indian states not in CI5.

    “The nationwide baseline risk reported here (11 cases per 100 000 woman-years) is lower than that in GLOBOCAN (18·0 cases per 100 000 woman-years),27 because we also included data from Indian states with relatively low cancer incidence that are not in CI5.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Ferlay, 2020

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Licensed prophylactic HPV vaccines protect against infection with vaccine-targeted HPV types, precancerous lesions, and invasive cervical cancer.

    “The licensed prophylactic human papillomavirus (HPV) vaccines protect against infection with vaccine-targeted HPV types, precancerous lesions, and invasive cervical cancer, have demonstrated high efficacy for three-dose and two-dose schedules,3, 4 and have consistently been shown to be safe.5”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    A single-dose HPV immunisation schedule could facilitate scale-up of HPV vaccination and contribute to global elimination of cervical cancer.

    “A single-dose immunisation schedule could facilitate the scale-up of human papillomavirus (HPV) vaccination, contributing to global elimination of cervical cancer.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The very high burden of cervical cancer in India underpins the urgency to upscale key interventions, including HPV vaccination, cervical cancer screening, appropriate treatment, and palliative care.

    “The very high burden of cervical cancer in India underpins the urgency to upscale key interventions, including vaccination against HPV, cervical cancer screening, appropriate treatment, and palliative care, as recommended in the WHO strategy towards the elimination of cervical cancer as a public health problem.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    GLOBOCAN Cancer over time reports a baseline ASIR of 15 cases per 100,000 woman-years.

    “GLOBOCAN Cancer over time (15 cases per 100 000 woman-years).28”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Ervik, 2020

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Interpretationown data

    This study complements existing evidence that single-dose HPV vaccination could be an effective and efficient strategy for cervical cancer prevention in India and other low-income and middle-income settings.

    “This study complements existing evidence that single-dose HPV vaccination could be an effective and efficient strategy for cervical cancer prevention in India and other low-income and middle-income settings.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HPV vaccination is one of the key pillars, together with cervical cancer screening and treatment, in the WHO call to eliminate cervical cancer as a public health problem.

    “HPV vaccination is, therefore, one of the key pillars—together with cervical cancer screening and treatment—in the WHO call to eliminate cervical cancer as a public health problem.6”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] 2020

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    GLOBOCAN Cancer today reports a baseline ASIR of 18 cases per 100,000 woman-years.

    “as reported on GLOBOCAN Cancer today (18 cases per 100 000 woman-years)27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Ferlay, 2020

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Introduction of HPV vaccination into national immunisation programmes in India and other low-income and middle-income countries would be facilitated if a single dose of HPV vaccine were shown to be effective in preventing cervical cancer.

    “Introduction of HPV vaccination into national immunisation programmes in India, and other low-income and middle-income countries, would be facilitated if a single dose of HPV vaccine were shown to be effective in preventing cervical cancer.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    From April 2022, WHO SAGE recommended single-dose or two-dose schedules for the primary target group of girls aged 9-14 years and girls and women aged 15-20 years.

    “From April, 2022, the WHO Strategic Advisory Group of Experts on Immunization recommended single-dose or two-dose schedules for the primary target group of girls aged 9–14 years and girls and women aged 15–20 years.”
    • Also stated in: § Introduction · plain
      “Based on these considerations, in April, 2022, the WHO Strategic Advisory Group of Experts on Immunization updated their recommendation on HPV vaccination schedule to a single dose or two doses for the primary target of girls aged 9–14 years and for young women aged 15–20 years.13”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] 2022

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Using SLTR to define public health targets allows comparison against the highest observed life expectancy standards and provides an alternative standardisation not relying on outdated world population age distribution.

    “using SLTR to define public health targets allows comparison of actual or projected outcomes against the highest observed life expectancy standards, and provides an alternative approach to standardisation that does not rely on outdated world population age distribution.25”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Malagón, 2021, Invited commentary: rethinking cervical cancer elimination in terms of lifetime risk rather than arbitrarily defined age-standardized incidence rates, Am J Epidemiol source

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    A successfully implemented national HPV vaccination programme is expected to improve the health of the Indian population and generate useful lessons for implementing HPV vaccination in other low-income and middle-income countries.

    “if successfully implemented, a national HPV vaccination programme is expected to not only improve the health of the Indian population, but would also generate useful lessons for implementing HPV vaccination in other low-income and middle-income countries.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Under a range of plausible conditions of coverage and vaccine protection, single-dose HPV vaccination could be more efficient than a two-dose strategy in decreasing cervical cancer burden in India and could eliminate cervical cancer as a public health problem.

    “under a range of plausible conditions of coverage and vaccine protection, single-dose HPV vaccination could be more efficient in decreasing the burden of cervical cancer in India than a two-dose strategy, and could eliminate cervical cancer as a public health problem.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Premisecitation

    The success of HPV vaccination depends on securing political will and public acceptance.

    “the success of HPV vaccination depends on securing political will and public acceptance.9”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Sankaranarayanan, 2019, Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts, Lancet Oncol source

  • May combine two claims.

    Study design and conductown data

    The modelling study used a large amount of local data and evidence, making its results context specific.

    “A major strength of this modelling study is the amount of local data and evidence that make our results context specific.”
    Quote in the paperSubstantial claim
36 of 36

  • The authors state this as an assumption.

    Transmission of different high-risk HPV types is independent and governed by type-specific natural history parameters.

    “Transmission of different high-risk HPV types was assumed to be independent and governed by type-specific natural history parameters.”

  • The paper relies on this without support.

    High-quality HPV prevalence data needed to calibrate EpiMetHeos were not available for some states in India.

    “Because the high-quality data on HPV prevalence we needed to calibrate EpiMetHeos were not available for some states in India, we first identified clusters of states with similar patterns of cervical cancer incidence using Cancer Incidence in Five Continents (CI5; volume XI, for the period 2008–12) and the Indian National Centre for Disease Informatics and Research (NCDIR; for the period 2012–16).”

  • The paper relies on this without support.

    States within each identified cervical cancer incidence cluster are similar enough that HPV vaccination impact projections from the representative state can be extrapolated to other states in the same cluster.

    “Finally, we projected the effect of HPV vaccination on HPV infection and risk of cervical cancer for Tamil Nadu and West Bengal and extrapolated these projections to other states within each cluster.”

  • The authors state this as an assumption.

    Two-dose HPV vaccination provides life-long protection against vaccine-targeted HPV types.

    “Based on available evidence, we assumed life-long protection by two-dose vaccination throughout all scenarios.10”

  • The authors state this as an assumption.

    Single-dose HPV vaccination provides life-long protection for vaccine-targeted HPV types.

    “In the base-case scenario, we also assumed single-dose vaccination to provide life-long protection for vaccine-targeted HPV types derived from the near-zero number of breakthrough persistent infections up to 10 years after vaccination and stabilising antibody kinetics, as observed in the IARC India HPV vaccine trial for the quadrivalent vaccine.11”

  • The authors state this as an assumption.

    Vaccine efficacy under both single-dose and two-dose schedules is 95% for HPV16 and HPV18, 9% for HPV31, HPV33, and HPV45, and 0% for remaining high-risk HPV types.

    “On the basis of the same trial, we assumed vaccine efficacy under both single-dose and two-dose schedules to be 95% for HPV16 and HPV18; 9% for HPV 31, HPV33, and HPV45; and 0% for the remaining high-risk HPV types.”

  • The authors state this as an assumption.

    Under assumptions B, C, and D, remaining efficacy for HPV16 and HPV18 at 20 years after vaccination is approximately 80%, 75%, and 65%, respectively, with long-term efficacy plateauing above 50%.

    “Assumptions B, C, and D corresponded to remaining efficacy of approximately 80%, 75%, and 65% for HPV16 and HPV18 at 20 years after vaccination, respectively, with long-term efficacy plateauing above 50% for each of them.”

  • The authors state this as an assumption.

    Under assumption E, there is no cross-protection for HPV31, HPV33, and HPV45, while other parameters are as in assumption D.

    “The worst-case scenario, assumption E, corresponded with assumption D without cross-protection for HPV31, HPV33, and HPV45.”

  • The authors state this as an assumption.

    The same vaccine efficacy was assumed for all catch-up cohorts.

    “The same vaccine efficacy was assumed for all catch-up cohorts, although vaccine effectiveness in catch-up cohorts might be lower because the vaccine can only prevent newly acquired HPV infections.”

  • The authors state this as an assumption.

    No screening throughout all scenarios.

    “Because access to cervical cancer screening in India is very low, we assumed no screening throughout all scenarios.8”

  • The authors state this as an assumption.

    Life-long protection from HPV16 and HPV18 infection under both single-dose and two-dose schedules in the base-case scenario.

    “In the base-case scenario, assuming life-long protection from HPV16 and HPV18 infection under both single-dose and two-dose schedules”

  • The authors state this as an assumption.

    Single-dose and two-dose HPV vaccinations have the same long-lasting efficacy.

    “Assuming the same long-lasting efficacy of single-dose and two-dose vaccinations”
12 of 12

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Economic modeling suggests that inclusion of catch-up vaccination for older women can be a cost-effective way to decrease cervical cancer burden.

    “and economic modeling suggests that inclusion of catch-up vaccination for older women can be a cost-effective way to decrease cervical cancer burden [18, 19].”

    From Acceptability of HPV vaccination for cervical cancer prevention amongst emerging adult women in rural Mysore, India: a mixed-methods study (2024) · cites this paper as [18]

    The Discussion reports that catch-up vaccination in girls aged 11–20 years could be cost-effective, citing a separate unpublished economic analysis. The Results project reduced cervical cancer risk with catch-up vaccination extending to women aged 30, but the paper does not establish cost-effectiveness for those older cohorts. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • At the individual level, limited knowledge, cultural misconceptions, and attitudinal barriers such as fear of side effects or concerns about morality were key problems, especially among less educated or rural populations.

    “At the individual level, limited knowledge, cultural misconceptions, and attitudinal barriers, such as fear of side effects or concerns about morality were key problems, especially among less educated or rural populations12,14,17,19,28,37,38.”

    From Barriers to HPV vaccination among adolescent girls in India: A scoping review (2026) · cites this paper as [14]

    The Discussion (page unavailable) says HPV vaccination depends on public acceptance, which broadly supports the relevance of attitudes. It does not identify limited knowledge, cultural misconceptions, fear of side effects, or morality concerns as key problems, nor does it say these barriers are especially prevalent among less educated or rural populations. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Northern Indian states with higher religious conservatism exhibited lower HPV vaccine acceptability compared to more urbanized Southern states.

    “For instance, Northern states with higher religious conservatism exhibited lower vaccine acceptability compared to more urbanized Southern States14,22.”

    From Barriers to HPV vaccination among adolescent girls in India: A scoping review (2026) · cites this paper as [14]

    The Methods (Data sources and model calibration; page unavailable) group states by cervical cancer incidence, not vaccine acceptability. The Discussion mentions public acceptance as important but reports no North–South comparison or link to religious conservatism or urbanization. Searches for those terms and regional differences found no supporting passage in our copy. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Cites

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Related

Authors
Man, I., Georges, D., de Carvalho, T. M., Ray Saraswati, L., Bhandari, P., Kataria, I., Siddiqui, M., Muwonge, R., Lucas, E., Berkhof, J., Sankaranarayanan, R., Bogaards, J. A., Basu, P., & Baussano, I.
Affiliations
  • World Health Organization (CH)
  • RTI International (US)
  • Amsterdam Public Health (NL)
Corresponding author
Man, Irene
ORCID
Venue
The Lancet Oncology
Publisher
Elsevier BV
Published
2022-11
Volume
23
Issue
11
Pages
1419-1429
ISSN
1470-2045 (ISSN-L)
DOI
10.1016/s1470-2045(22)00543-5
PMC
PMC9622421
OpenAlex
W4297103078
Cited by
44
References
27
Citations by year
2026: 6 · 2025: 6 · 2024: 16 · 2023: 14 · 2022: 2
FWCI
5.80
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Oncology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • PubMed Central (submittedVersion, cc-by)
  • Pure Amsterdam UMC (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • Centre International de Recherche sur le Cancer
  • World Health Organization
  • Bill &amp; Melinda Gates Foundation (OPP48979, INV-039876)
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Women's cancer prevention and management
  • Health Sciences › Medicine › Surgery › Genital Health and Disease
Keywords
HPV vaccination, single-dose vaccination, quadrivalent HPV vaccine, cervical cancer elimination, HPV prevalence, vaccination coverage, catch-up vaccination, India, sexual behavior, cervical cancer incidence, vaccine protection duration
MeSH terms
Uterine Cervical Neoplasms, Female, Humans, India, Papillomavirus Infections, Human papillomavirus 16, Papillomavirus Vaccines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-16.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-16.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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