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Cited by 132Cervical Cancer and HPV ResearchWomen's cancer prevention and managementHealth Systems, Economic Evaluations, Quality of Life

Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India

Open access
Diaz, M, Kim, J J, Albero, G, de Sanjosé, S, Clifford, G, Bosch, F X, Goldie, S J·2008·British Journal of Cancer
DOI 10.1038/sj.bjc.6604462PMC PMC2480962
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Abstract

Cervical cancer is a leading cause of cancer death among women in low-income countries, with approximately 25% of cases worldwide occurring in India. We estimated the potential health and economic impact of different cervical cancer prevention strategies. After empirically calibrating a cervical cancer model to country-specific epidemiologic data, we projected cancer incidence, life expectancy, and lifetime costs (I$2005), and calculated incremental cost-effectiveness ratios (I$/YLS) for the following strategies: pre-adolescent vaccination of girls before age 12, screening of women over age 30, and combined vaccination and screening. Screening differed by test (cytology, visual inspection, HPV DNA testing), number of clinical visits (1, 2 or 3), frequency (1 x , 2 x , 3 x per lifetime), and age range (35-45). Vaccine efficacy, coverage, and costs were varied in sensitivity analyses. Assuming 70% coverage, mean reduction in lifetime cancer risk was 44% (range, 28-57%) with HPV 16,18 vaccination alone, and 21-33% with screening three times per lifetime. Combining vaccination and screening three times per lifetime provided a mean reduction of 56% (vaccination plus 3-visit conventional cytology) to 63% (vaccination plus 2-visit HPV DNA testing). At a cost per vaccinated girl of I$10 (per dose cost of $2), pre-adolescent vaccination followed by screening three times per lifetime using either VIA or HPV DNA testing, would be considered cost-effective using the country's per capita gross domestic product (I$3452) as a threshold. In India, if high coverage of pre-adolescent girls with a low-cost HPV vaccine that provides long-term protection is achievable, vaccination followed by screening three times per lifetime is expected to reduce cancer deaths by half, and be cost-effective.

AI snapshot

Written from the paper’s full text.

TL;DR

This modeling study projected that in India, pre-adolescent HPV 16/18 vaccination plus screening three times per lifetime could substantially reduce cervical cancer burden and be cost-effective if the vaccine is very low-cost. At a cost per vaccinated girl of I$10 (about $2 per dose), vaccination followed by VIA or HPV DNA screening was expected to be cost-effective using India’s per capita GDP (I$3452) as a threshold.

Key findings

  • Assuming 70% coverage, pre-adolescent HPV 16/18 vaccination alone reduced mean lifetime cervical cancer risk by 44% (range, 28–57%); screening three times per lifetime reduced risk by 21–33%.
  • Combining vaccination with screening three times per lifetime gave a mean reduction of 56% (vaccination plus 3-visit conventional cytology) to 63% (vaccination plus 2-visit HPV DNA testing).
  • At I$10 per vaccinated girl, vaccination followed by screening three times per lifetime using VIA cost I$290 per year of life saved (YLS); at I$20 per vaccinated girl, single-visit VIA screening alone cost I$60 per YLS compared with no intervention and became more cost-effective than vaccination alone.
  • At a vaccine price of about $100 per dose (I$360 per vaccinated girl), vaccination was dominated by screening alone; combined vaccination plus single-visit VIA rose to I$7230 per YLS. If only HPV DNA testing was available, screening alone was dominated below I$50 per vaccinated girl, and combined vaccination plus two-visit HPV DNA testing three times per lifetime was I$1780 per YLS across that range.

Methods

  • An individual-based stochastic microsimulation model of cervical carcinogenesis was calibrated to country-specific epidemiologic data from southeastern India, including HPV prevalence and type distribution from Tamil Nadu and cancer incidence from Bangalore and Chennai registries; a single birth cohort of girls entered at age 9 and was followed for life.
  • Strategies compared were pre-adolescent HPV 16/18 vaccination before age 12, screening of women over age 30 by cytology, VIA, or HPV DNA testing with varying visits, frequency, and ages, and combined vaccination plus screening; base case assumed 70% coverage, screening at ages 35, 40, and 45, 3% annual discounting, societal perspective, and costs in I$2005.
  • Outcomes were cancer incidence reduction, life expectancy gains, discounted lifetime costs, and incremental cost-effectiveness ratios (I$/YLS), with one-way, two-way, and probabilistic sensitivity analyses across good-fitting parameter sets.

Limitations

  • The paper states that model parameter uncertainty remains, especially about HPV natural history in older women, type-specific immunity after natural infection, and multiple HPV infections; lack of high-quality temporal trend data limited calibration to a single birth cohort.
  • The authors state they used a microsimulation model rather than an HPV transmission model, so herd immunity was not directly modeled, and they describe the findings as exploratory and cost-effectiveness estimates as approximate; affordability was not equivalent to cost-effectiveness.
  • Evident from the text: base-case results assume lifelong vaccine protection and 70% coverage, use cost estimates from a prior India screening analysis, and assume 15% loss to follow-up between visits; actual vaccine price and programmatic delivery costs in India were unknown.

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

Integrity signals

Registry

Crossref · 10.1038/sj.bjc.6604462

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

2 of 30 cited sources checked · 0 supported · 1 flagged · accuracy not yet measured

  • Study design and conductcitation

    Sensitivity analyses that reduced incidence based on herd immunity findings found the main policy results would be unlikely to change.

    “While our independent dynamic model (Kim et al, 2007b) has been previously used to include the herd immunity effects in an HPV vaccine policy analysis, sensitivity analyses that reduced incidence based on these findings, found the main policy results would be unlikely to change.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Kim et al, 2007b source

      The Methods (Dynamic model; page unavailable) say that projected reductions in HPV incidence, including herd-immunity effects, were used as inputs to the policy model. The Results report sensitivity analyses and the Discussion favours prioritising vaccination of girls, but our copy does not identify a sensitivity analysis that reduced incidence based on those herd-immunity findings or state that such an analysis left the main policy results unchanged. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Findingown data

    Pre-adolescent vaccination alone is more effective than screening alone.

    “Pre-adolescent vaccination alone reduced cancer incidence by 44% (range, 28–57%) and was more effective than screening alone (Figure 2, upper panel).”
    Quote in the paperSubstantial claim
  • Findingown data

    At vaccine price ~$100 per dose (I$360 per vaccinated girl), vaccination is dominated by screening alone.

    “At a vaccine price per dose of approximately $100 (I$360 per vaccinated girl), vaccination was dominated by (i.e., either less costly and less cost-effective than or more costly and less effective than) screening alone.”
    Quote in the paperSubstantial claim
  • Findingown data

    Without screening, a threshold of 50% cancer reduction is expected to be attainable with vaccination alone only at vaccination coverage >80% and vaccine efficacy 100%.

    “For example, without screening, a threshold of 50% cancer reduction (dashed red line) was expected to be attainable with vaccination alone only at vaccination coverage rates exceeding 80% and vaccine efficacy of 100%.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Assuming 70% coverage, HPV 16,18 vaccination alone reduces lifetime cancer risk by 44% (range 28-57%).

    “Assuming 70% coverage, mean reduction in lifetime cancer risk was 44% (range, 28–57%) with HPV 16,18 vaccination alone”
    • Also stated in: § Reduction in lifetime risk of cancer · plain
      “Pre-adolescent vaccination alone reduced cancer incidence by 44% (range, 28–57%)”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The mechanism of cervical carcinogenesis does not fundamentally differ between countries.
    • The authors state this as an assumption: Vaccinated girls have life-long protection against HPV 16 and 18.
    • The authors state this as an assumption: Vaccinated girls are subject to the same rate of infection with other high-risk HPV types as those who are not vaccinated.
  • May combine two claims. 25
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 21

  • May combine two claims.

    Study design and conductcitation

    The individual-based microsimulation model was chosen over the HPV 16 and 18 transmission model because the former can simulate detailed screening strategies as well as vaccination, and includes other HPV types not targeted by the vaccine, enabling calibration to many epidemiological targets.

    “This was a purposeful decision as the former can simulate detailed screening strategies as well as vaccination, and includes other HPV types not targeted by the vaccine, enabling us to take advantage of all available data by calibrating to many epidemiological targets (Garnett et al, 2006).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Kim et al, 2007b source

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

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites Garnett et al, 2006 source

  • May combine two claims.

    Findingown data

    Across vaccine costs I$10-I$50, pre-adolescent vaccination combined with two-visit HPV DNA testing three times per lifetime costs I$1780 per YLS; at I$360 per vaccinated girl, this strategy increases to I$7650 per YLS compared to next best.

    “Across this same range of vaccine costs, pre-adolescent vaccination combined with two-visit HPV DNA testing three times per lifetime was I$1780 per YLS; at higher costs (I$360 per vaccinated girl) this strategy increased to I$7650 per YLS, compared to the next best strategy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Assuming cost I$20 per vaccinated girl, if VIA screening is 30% less sensitive and costs increased to I$2, vaccination alone dominates VIA screening, although VIA combined with vaccination approximates I$975 per YLS.

    “Assuming a cost of I$20 per vaccinated girl, if VIA screening was 30% less sensitive and costs were increased to I$2, vaccination alone dominated VIA screening, although VIA combined with vaccination approximated I$975 per YLS (see Supplementary Appendix).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    When cost per vaccinated girl ≥ I$20, screening three times per lifetime (ages 35, 40, 45) with single-visit VIA is less costly and more cost-effective than vaccination alone, costing I$60 per YLS compared to no intervention.

    “When the cost per vaccinated girl reached and exceeded I$20, screening three times per lifetime (at ages 35, 40, and 45) with a single-visit VIA strategy was less costly and more cost-effective than vaccination alone, and cost I$60 per YLS compared to no intervention.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Screening three times per lifetime reduces lifetime cancer risk by 21-33%.

    “and 21–33% with screening three times per lifetime.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The mechanism of cervical carcinogenesis does not fundamentally differ between countries.

  • May combine two claims.

    Findingown data

    A combined strategy of vaccination and screening always provides greater cancer reduction than vaccination alone; the incremental benefits of adding screening three times per lifetime are greater at lower vaccination coverage rates.

    “A combined strategy of vaccination and screening always provided greater cancer reduction than vaccination alone; however, the incremental benefits achieved by adding screening three times per lifetime were greater at lower vaccination coverage rates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Assuming all strategies equally available and cost per vaccinated girl ≤ I$10, vaccination alone is more effective and cost-effective than screening alone.

    “Assuming that all strategies were equally available (Table 2a) and provided the cost per vaccinated girl was I$10 ($2 per dose) or less, vaccination alone was more effective and cost-effective than screening alone.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    If training costs associated with VIA raise total screening cost to approach HPV DNA testing, vaccination plus screening three times per lifetime with two-visit HPV DNA testing is favored at I$1780 per YLS; if rapid HPV DNA test allows single-visit screen-and-treat, this result becomes more favourable.

    “For example, if training costs associated with VIA raised the total screening cost such that it would approach that of HPV DNA testing, vaccination plus screening three times per lifetime with two-visit HPV DNA testing was favored, at I$1780 per YLS – if a rapid HPV DNA test was available, allowing for a single-visit screen-and-treat strategy, this result would become even more favourable.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At vaccination coverage 40-50%, screening coverage would need to exceed 80% to achieve 50% cancer reduction; at vaccination coverage 70%, screening coverage 40-50% would suffice.

    “At vaccination coverage rates of 40–50%, screening coverage would need to exceed 80%, but at vaccination coverage of 70%, screening coverage of 40–50% would suffice.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Per 1000 girls vaccinated, 15 deaths would be averted, compared with 3 deaths prevented per 1000 children vaccinated for rotavirus.

    “For example, we found that per 1000 girls vaccinated, 15 deaths would be averted (Goldie et al. 2008 in press), which compares favourably to 3 deaths prevented per 1000 children vaccinated for rotavirus (IAVI/PATH, 2007).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Goldie et al. 2008 in press source
    • cites IAVI/PATH, 2007

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

  • May combine two claims.

    Findingcitation

    A small expected increase in non-16,18 cancers was previously documented, and the impact on the main cost-effectiveness results was small.

    “We have previously documented a small expected increase in non-16,18 cancers (Goldie et al, 2003, 2007), although we again found that the impact on the main cost-effectiveness results was small.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Goldie et al, 2003, 2007

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

  • May combine two claims.

    Findingown data

    The rank-ordering of screening strategies from most effective to least effective was two-visit HPV DNA testing, single-visit VIA, and three-visit cytology; differences between these approaches were somewhat attenuated at higher vaccination coverage rates.

    “Although the rank-ordering of screening strategies from most effective to least effective, was two-visit HPV DNA testing, single-visit VIA, and three-visit cytology, differences between these screening approaches were somewhat attenuated at higher vaccination coverage rates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Across good-fitting parameter sets, mean cancer reduction with vaccination alone ranges from 28 to 57%, whereas combined vaccination and screening three times per lifetime using two-visit HPV DNA testing ranges from 53 to 76%.

    “For example, across the good-fitting parameter sets, the mean cancer reduction with vaccination alone ranged from 28 to 57%, whereas with combined vaccination and screening three times per lifetime using two-visit HPV DNA testing ranged from 53 to 76%.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Vaccination prevents infections with HPV types 16 and 18.
    • Rests on an assumption: Screening allows for treatment of precancerous lesions (caused by any high-risk HPV type) before progression to invasive cancer.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    The analysis followed published recommendations for economic evaluations by adopting a societal perspective and discounting future costs and life years by 3% annually.

    “We followed published recommendations for economic evaluations (DCPP; Gold et al, 1996; Drummond et al, 2005; WHO CHOICE) by adopting a societal perspective and discounting future costs and life years by 3% annually.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Gold et al, 1996

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

    • cites Drummond et al, 2005 source
    • cites WHO CHOICE

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

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Cost-effectiveness analyses were conducted with a random sample of good-fitting parameter sets, and results were reported as mean and range.

    “To explicitly incorporate the effect of parameter uncertainty, cost-effectiveness analyses were conducted with a random sample of good-fitting parameter sets, and results were reported as the mean and range of outcomes, whereas incremental cost-effectiveness ratios were reported as the ratio of the mean costs divided by the mean effects of one strategy vs another across the good-fitting parameter”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Age-adjusted cervical cancer incidence rates in India vary between regions, ranging from 10.9 in Trivandrum to 47.2 per 100,000 person-years at risk in Chennai.

    “Although cervical cancer is the most frequent cancer diagnosis in Indian women, age-adjusted incidence rates vary between regions, ranging from 10.9 in Trivandrum to 47.2 per 100 000 person-years at risk in Chennai (Parkin et al, 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Parkin et al, 2005

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

  • May combine two claims.

    Interpretationreasoning

    In India, if high coverage of pre-adolescent girls with a low-cost HPV vaccine that provides long-term protection is achievable, vaccination followed by screening three times per lifetime is expected to reduce cancer deaths by half and be cost-effective.

    “In India, if high coverage of pre-adolescent girls with a low-cost HPV vaccine that provides long-term protection is achievable, vaccination followed by screening three times per lifetime is expected to reduce cancer deaths by half, and be cost-effective.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The mechanism of cervical carcinogenesis does not fundamentally differ between countries.
    • The authors state this as an assumption: Vaccinated girls have life-long protection against HPV 16 and 18.
    • The authors state this as an assumption: Vaccinated girls are subject to the same rate of infection with other high-risk HPV types as those who are not vaccinated.

  • Classified as probably not a substantial claim.

    Premisecitation

    One suggested heuristic for cost-effectiveness threshold is to use the country's per capita GDP.

    “Although there is no consensus on a specific cost-effectiveness threshold, below which an intervention would be considered cost-effective, one suggested heuristic has been to use the country's per capita GDP (WHO, 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites WHO, 2001

      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

    Cervical cancer is the most frequent cancer diagnosis in Indian women.

    “Although cervical cancer is the most frequent cancer diagnosis in Indian women, age-adjusted incidence rates vary between regions, ranging from 10.9 in Trivandrum to 47.2 per 100 000 person-years at risk in Chennai (Parkin et al, 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Parkin et al, 2005

      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

    More than 25% of cervical cancer cases worldwide occur in India.

    “More than 25% of cervical cancer cases worldwide occur in India (Ferlay et al, 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ferlay et al, 2004

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

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Parameter uncertainty was evaluated using one- and two-way sensitivity analysis, and probabilistic analysis.

    “Parameter uncertainty was evaluated using one- and two-way sensitivity analysis, and probabilistic analysis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The model includes vaccine-targeted and non-targeted HPV types, allowing exploration of the potential effect of an increase in non-vaccine-targeted HPV types.

    “As the model includes vaccine-targeted and non-targeted HPV types, we were able to explore the potential effect of an increase in non-vaccine-targeted HPV types.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    On the basis of age-specific incidence and projected demographic changes, expected new cases of cervical cancer in India will increase from 132,082 in 2002 to more than 330,000 in 2050.

    “On the basis of age-specific incidence and projected demographic changes, the expected new cases of cervical cancer in India will increase from 132 082 in year 2002, to more than 330 000 in 2050 (Ferlay et al, 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ferlay et al, 2004

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

  • May combine two claims.

    Interpretationreasoning

    Vaccination and screening are synergistic and provide substantially greater benefits than either alone.

    “they are synergistic, and provide substantially greater benefits than either alone.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Vaccination prevents infections with HPV types 16 and 18.
    • Rests on an assumption: Screening allows for treatment of precancerous lesions (caused by any high-risk HPV type) before progression to invasive cancer.

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

    Interpretationnone given

    The strategies identified as cost-effective in this analysis may still be prohibitively expensive in India.

    “The strategies that we have identified as cost-effective in this analysis may still be prohibitively expensive in India”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The effectiveness of the vaccine could be lower than projected if there is less robust vaccine-induced immunity in girls with other diseases, such as severe anaemia, chronic illness or HIV.

    “if there is less robust vaccine-induced immunity in girls with other diseases, such as severe anaemia, chronic illness or HIV”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    For most of these factors, a lack of data prohibits estimating the magnitude of individual potential effects; these are uncertain issues for which empiric data are needed.

    “For most of these factors, a lack of data prohibit us from estimating the magnitude of individual potential effects; that being said, these are uncertain issues for which empiric data are needed.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Prevention and treatment of cervical cancer, the leading cause of cancer in Indian women, is a priority according to India's National Cancer Control Programme.

    “Prevention and treatment of cervical cancer, the leading cause of cancer in Indian women, is a priority according to the country's National Cancer Control Programme (Government of India, 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Government of India, 2005

      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).

    Interpretationnone given

    The impact of the vaccine could be higher if there are herd immunity benefits to unvaccinated individuals.

    “if there are herd immunity benefits to unvaccinated individuals”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The I$290 per YLS ratio for combined vaccination and VIA screening is a fraction of India's per capita GDP and would be considered very cost-effective according to suggested benchmarks for developing countries.

    “this ratio is a fraction of India's per capita GDP, and would be considered very cost-effective according to suggested benchmarks for developing countries (WHO, 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites WHO, 2001

      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).

    Interpretationreasoning

    If a cytology-based strategy could be conducted in two visits without colposcopy for diagnostic confirmation, it could be more attractive than predicted by the analysis due to reduced loss to follow-up.

    “If a cytology-based strategy could be conducted in two visits without the use of colposcopy for diagnostic confirmation, it could be more attractive than predicted by our analysis due to reduced loss to follow-up.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    The analysis has several limitations, and the results are intended to provide quantitative approximations of the potential benefits of HPV vaccination and qualitative insight into the relative value of primary and secondary prevention.

    “Our analysis has several limitations, and thus, we emphasise that our results are intended to provide quantitative approximations of the potential benefits of HPV vaccination, and to provide qualitative insight into the relative value of primary and secondary prevention.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Given the range of uncertainties and limitations, the findings should be considered exploratory and the cost-effectiveness estimates approximate.

    “Given the range of uncertainties and the limitations of this analysis, our findings should be considered exploratory and our estimates of cost-effectiveness approximate, and should be interpreted in the context of the analytic purpose of this work, that is, to leverage the best available data to provide insight into decisions that policy makers in India are discussing right now.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The impact of the vaccine could be higher if there is long-term cross-protection against non-16,18 type infection.

    “the impact of the vaccine could be higher if there is long-term cross-protection against non-16,18 type infection”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    A lack of high quality data on temporal trends of HPV-related disease limited the ability to calibrate the model to different time points and contributed to the choice to simulate a single birth cohort.

    “Similarly, a lack of high quality data on temporal trends of HPV-related disease limited our ability to calibrate the model to different time points, and contributed to the choice to simulate a single birth cohort.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    The effectiveness of the vaccine could be lower than projected if vaccine-induced immunity wanes while individuals are still at risk for new HPV infections.

    “or if vaccine-induced immunity wanes while individuals are still at risk for new HPV infections.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The impact of the vaccine could be higher if non-cervical HPV 16,18-related cancers and diseases are prevented.

    “and if non-cervical HPV 16,18-related cancers and diseases are prevented.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    There are uncertainties with respect to the natural history of HPV, especially in older women, the nature of type-specific immunity following natural infection, and the relationships between different HPV types in multiple infections.

    “In addition to model parameter uncertainty, there are uncertainties with respect to the natural history of HPV, especially in older women, the nature of type-specific immunity following natural infection, and the relationships between different HPV types in the case of multiple infections.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The effectiveness of the vaccine could be lower than projected if older girls who may have been infected previously with type 16 or 18 are vaccinated.

    “The effectiveness of the vaccine could be lower than we projected if older girls, who may have been infected previously with type 16 or 18, are vaccinated”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Screening three times per lifetime prevents additional deaths from non-16 and 18-type associated cancers, as well as 16,18-associated cancers in the unvaccinated proportion, and provides insurance of cancer risk protection given uncertainty around long-term vaccine performance.

    “Although screening three time per lifetime prevents additional deaths from non-16 and 18-type associated cancers, as well as 16,18-associated cancers in the proportion of the population not vaccinated, it also provides some insurance of cancer risk protection in the context of the uncertainty around long-term vaccine performance in a non-clinical trial situation.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Screening allows for treatment of precancerous lesions (caused by any high-risk HPV type) before progression to invasive cancer.
40 of 40

  • The authors state this as an assumption.

    The mechanism of cervical carcinogenesis does not fundamentally differ between countries.

    “We assumed that the mechanism of cervical carcinogenesis does not fundamentally differ between countries; as such, initial natural history model estimates, and their plausible ranges, were based on the best available data regardless of specific setting.”

  • The authors state this as an assumption.

    Vaccinated girls have life-long protection against HPV 16 and 18.

    “We also assumed vaccinated girls have life-long protection against HPV 16 and 18, but are subject to the same rate of infection with other high-risk HPV types as those who are not vaccinated.”

  • The authors state this as an assumption.

    Vaccinated girls are subject to the same rate of infection with other high-risk HPV types as those who are not vaccinated.

    “We also assumed vaccinated girls have life-long protection against HPV 16 and 18, but are subject to the same rate of infection with other high-risk HPV types as those who are not vaccinated.”

  • The paper relies on this without support.

    Vaccination prevents infections with HPV types 16 and 18.

    “with vaccination preventing infections with HPV types 16 and 18”

  • The paper relies on this without support.

    Screening allows for treatment of precancerous lesions (caused by any high-risk HPV type) before progression to invasive cancer.

    “screening allowing for treatment of precancerous lesions (caused by any high-risk HPV type) before progression to invasive cancer”

  • The paper relies on this without support.

    The vast majority of women will lack curative treatment, and approximately two-thirds will die from cervical cancer.

    “The vast majority of women will lack curative treatment, and thus, approximately two-thirds will die from this preventable disease.”

  • The paper relies on this without support.

    Women who will benefit from vaccination are not in the same birth cohorts as the women who benefit from screening in the short-run.

    “women who will benefit from vaccination are not in the same birth cohorts as the women who benefit from screening in the short-run”

  • The paper relies on this without support.

    The vaccine-preventable cervical cancer burden in India is a product of underlying cervical cancer incidence, the proportion of cancer attributable to HPV 16 and 18, long-term vaccine efficacy, and ability to achieve high coverage in adolescent girls before sexual activity.

    “The vaccine-preventable cervical cancer burden in India is a product of several factors, including the underlying cervical cancer incidence, the proportion of cancer attributable to HPV 16 and 18, the long-term vaccine efficacy, and the ability to achieve high coverage in adolescent girls before sexual activity.”
8 of 8

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  • Using an individual based stochastic model for India, Diaz et al (2008) reported mean cancer reduction as 29%, 21% and 33% when women were screened thrice per lifetime with VIA, cytology and HPV DNA, respectively.

    “Using an individual based stochastic model for India, Diaz et al (2008) reported mean cancer reduction as 29%, 21% and 33%, when women were screened thrice per lifetime with VIA, cytology and HPV DNA, respectively. [47]”

    From Cost effectiveness of strategies for cervical cancer prevention in India (2020) · cites this paper as [47]

    The Abstract reports a 21–33% mean reduction in lifetime cancer risk with screening three times per lifetime, and the Methods describe an individual-based stochastic model calibrated to Indian data. The Discussion ranks HPV DNA testing above VIA above cytology, consistent with the claimed ordering, but our copy does not state the specific 29% reduction for VIA or explicitly assign the 21% and 33% figures to cytology and HPV DNA testing. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • 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.”

    From Evidence-based impact projections of single-dose human papillomavirus vaccination in India: a modelling study (2022) · cites this paper as [32]

    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

  • Screening three times in a lifetime reduces cervical cancer risk by 21-33%.

    “Screening three times in a lifetime reduces cervical cancer risk by 21-33% (Diaz et al., 2008).”

    From Indian Parents Prefer Vaccinating their Daughters against HPV at Older Ages (2014) · cites this paper as Diaz et al., 2008

  • Our cost estimates were higher than what was reported by Diaz et al and Goldie et al even after adjustment of latter estimates for inflation since the year of estimation.

    “However, our cost estimates were higher than what was reported by Diaz et al and Goldie et al even after adjustment of latter estimates for inflation since the year of estimation. [47, 48].”

    From Cost effectiveness of strategies for cervical cancer prevention in India (2020) · cites this paper as [47]

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Bhatla N, Ramachandran S, Virmani A, Arora VK, Gulati A, Singla S, Kriplani A, Bell L, Sellors J, Lorincz A, Eder P (2007) Correlation of FastHPV and Cytology: Performance trial results from India. 24th International Papillomavirus Conference and Clinical Workshop, November 3–9 2007, Beijing, China, 1C-03
  2. Ramachandran S, Bhatla N, Virmani A, Bell L, Payne E, Dong L, Chen G, Sellors J, Lorincz A, Eder P (2007) A fast affordable sensitive test for Hpv in developing countries: performance trial results from India. 24th International Papillomavirus Conference and Clinical Workshop, November 3–9, 2007, Beijing, China, PS6-59

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Related

Authors
Diaz, M., Kim, J. J., Albero, G., de Sanjosé, S., Clifford, G., Bosch, F. X., & Goldie, S. J.
Affiliations
  • Harvard University (US)
  • Institut Català d'Oncologia (ES)
  • Centre international de recherche sur le cancer (FR)
Corresponding author
Goldie, S J
ORCID
Venue
British Journal of Cancer
Publisher
Springer Science and Business Media LLC
Published
2008-07
Volume
99
Issue
2
Pages
230-238
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
DOI
10.1038/sj.bjc.6604462
PMC
PMC2480962
OpenAlex
W1987323551
Semantic Scholar
8c34bd3b6bae21af6572788bf120992d70c59ffe
Cited by
132
References
30
Citations by year
2026: 1 · 2025: 2 · 2024: 10 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 14 · 2016: 9 · 2015: 12 · 2014: 3 · 2013: 14 · 2012: 8
FWCI
7.44
Type
journal article
Language
en
Open access
Licence
Locations
  • British Journal of Cancer (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
Funders
Bill and Melinda Gates Foundation (30505)
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
  • Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Health Systems, Economic Evaluations, Quality of Life
Keywords
cervical cancer, cervical cancer screening, cost-effectiveness, HPV testing, visual inspection with acetic acid, cytology, cancer incidence, life expectancy, lifetime costs, cancer prevention, India
MeSH terms
Uterine Cervical Neoplasms, Cost-Benefit Analysis, DNA, Viral, Female, Humans, India, Mass Screening, Risk Factors, Stochastic Processes, Vaccination, Models, Statistical, Models, Economic, Papillomavirus Infections, Human papillomavirus 18, 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.

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