CoChat
Sign Up
Cited by 75Cervical Cancer and HPV ResearchHealth Systems, Economic Evaluations, Quality of LifeWomen's cancer prevention and management

Cost effectiveness of strategies for cervical cancer prevention in India

Open access
Chauhan, Akashdeep Singh, Prinja, Shankar, Srinivasan, Radhika, Rai, Bhavana, Malliga, JS, Jyani, Gaurav, Gupta, Nidhi, Ghoshal, Sushmita·2020·PLOS ONE
DOI 10.1371/journal.pone.0238291PMC PMC7462298
Open this paper in CoChat — free accountOpen PDF

Abstract

The establishment of link between high-risk human papillomavirus (HPV) infection and occurrence of cervical cancer has resulted in development of various HPV related control strategies for the prevention of cervical cancer. The objective of the present study was to assess the cost effectiveness of various screening strategies for cervical cancer and human papilloma virus (HPV) vaccination in India. A Markov model based on societal perspective was designed to estimate the lifetime costs and consequences of screening (with either visual inspect with acetic acid (VIA), Papanicolaou test or HPV DNA test at various time intervals) in a hypothetical cohort of 30-65 years age women or vaccination among adolescent girls. Diagnostic accuracy of the screening strategies, efficacy of HPV vaccination and data on transition probabilities was based on the results of the existing meta-analyses. Primary data was collected for assessing per person cost of screening, cost of treating cervical cancer and quality of life. We found that introduction of different screening strategies leads to reduction in lifetime occurrence of cervical cancer cases caused by HPV 16/18 from 20% to 61%, and cervical cancer deaths from 28% to 70%, as compared to no screening. Among various screening strategies, screening with both VIA 5 yearly and VIA 10 yearly came out to be cost effective at 1-time per capita GDP, with VIA every 5 years providing greater health benefits as compared to VIA 10 years. Hence, screening with VIA 5 years at an incremental cost of US$ 829 (INR 54,881) per QALY gained is the recommended strategy for India. Further, with regards to HPV vaccination, it leads to 60% reduction in cancer cases and mortality caused by HPV 16/18 as compared to no vaccination. Moreover, when this vaccinated cohort of adolescent girls is also screened later in their life (with VIA every 10 years and VIA 5 years), it leads to 69%-76% reduction in cancer cases and 71%-81% reduction in cancer deaths. As compared to no vaccination and no screening, both HPV vaccination alone and vaccination plus screening (with VIA every 5 yearly and VIA 10 yearly) appears to be cost effective with ICERs in the range of US$ 86 (INR 5,693) to US$ 476 (INR 31,511) per QALY gained. In the long run, when the cohort of adolescent girls, who were immunized for HPV, reach the age of 30 years, the screening frequency using VIA should be determined based on the coverage of HPV vaccination in that cohort.

AI snapshot

Written from the paper’s full text.

TL;DR

This Markov cost-utility analysis from a societal perspective in India found VIA every 5 years to be the most cost-effective cervical cancer screening strategy, and HPV vaccination alone or combined with later VIA screening to be cost-effective. It recommends VIA 5-yearly for India’s NPCDCS program and reassessment after 15 years for cohorts vaccinated as adolescents.

Key findings

  • In a cohort of 100,000 women aged 30 years, no screening led to 2,090 cervical cancer cases and 1,650 deaths; screening reduced cases by 20%–61% and deaths by 28%–70%. VIA every 5 years was most cost-effective at an incremental cost of US$ 829 (INR 54,881) per QALY gained, below India’s GDP per capita of US$ 1,890 in 2016–17.
  • Pap smear at any frequency was dominated; HPV DNA every 5 and 10 years was extendedly dominated. VIA every 5 years provided greater health benefits than VIA every 10 years.
  • HPV vaccination alone reduced HPV 16/18 cancer cases and deaths by 60%; vaccination plus VIA every 10 years reduced cases by 69% and deaths by 71%, while vaccination plus VIA every 5 years reduced cases by 76% and deaths by 81%. ICERs for vaccination alone and vaccination plus screening ranged from US$ 86 (INR 5,693) to US$ 476 (INR 31,511) per QALY gained versus no vaccination and no screening.
  • VIA every 5 years ceased to be cost-effective if treatment coverage fell below 30%, lifetime cervical cancer risk fell below 0.70%, or VIA sensitivity fell below 17%; vaccination alone ceased to be cost-effective if lifetime risk fell below 0.15%. At HPV vaccination coverage of 50% and 30%, vaccination plus VIA every 5 years became cost-effective versus vaccination plus VIA every 10 years, with ICERs of US$ 1,427 and US$ 1,168 per QALY gained.

Methods

  • Model-based cost-utility analysis using a Markov model with a societal perspective, 1-year cycle length, lifetime horizon, and 3% discounting. Hypothetical cohorts were 30-year-old women for screening and 11-year-old girls for vaccination; outcomes included cancer incidence, mortality, life-years, and QALYs.
  • Compared VIA, Pap smear, and HPV DNA testing at 3-, 5-, and 10-year intervals versus no screening, plus HPV vaccination alone and vaccination combined with later screening. Assumed screening coverage 80%, HPV vaccination coverage 70%, and 10% loss each from screen-positive to colposcopy and to treatment.
  • Parameters were drawn from meta-analyses, Indian cancer registries, an Indian RCT, and primary cost and EQ-5D-5L data (223 cervical cancer patients for HRQoL; 237 patients for out-of-pocket expenditure). Probabilistic sensitivity analysis used 999 Monte Carlo simulations, with threshold and subgroup analyses.

Limitations

  • The paper states that some natural-history parameters were derived from a mathematical model by Myers et al. because Indian empirical estimates for undiagnosed cancer progression and symptom probability were unavailable; age-specific HPV incidence was also derived from a vaccinated adolescent cohort.
  • The paper states that it omitted cervical cancers caused by HPV types other than 16/18, likely underestimating disease reduction, and that it did not use a dynamic transmission model, so herd immunity effects of vaccination were not accounted for.
  • The paper states that for combined vaccination and screening, the model did not capture benefits from detecting non-HPV 16/18 cancers in vaccinated women and underestimated about 8% of cases that the combined policy would prevent; evident from the text, the analysis remains model-based with assumed coverage, referral, and loss-to-follow-up parameters.

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

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0238291

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

18 of 41 cited sources checked · 10 supported · 0 flagged · accuracy not yet measured

  • Study design and conductcitation

    Cost of treatment for cervical cancer was based on primary data collected from a large public sector tertiary care hospital in North India for 2016-17.

    “The cost of treatment for cervical cancer was based on the primary data collected from a large public sector tertiary care hospital in North India for the year 2016–17. [38]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [38] MP Singh, 2020, Cost of Treatment for Cervical Cancer in India, Asian Pac J Cancer Prev source
  • Findingreasoning

    The incidence rate of HPV infection among unvaccinated 20-25-year-old women was computed as 11.6%.

    “Using the reported annual incidence rate of 0.8% for the HPV infection (HPV 16 and 18) among 20–25 year old immunized women with 2 doses of HPV vaccine [28] and vaccine efficacy of 93%, [29] we computed the incidence rate of HPV infection as 11.6% among unvaccinated cohort of the same age group.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [28] R Sankaranarayanan, 2016, Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study, Lancet Oncol source

      The citing sentence says its authors computed 11.6% using figures cited separately; it does not attribute that calculation to this paper. The paper’s Results report HPV infections in vaccinated groups, while its Discussion mentions a 3–9% frequency of HPV 16/18 infection in unvaccinated young women. Neither passage gives an 11.6% incidence rate for unvaccinated women aged 20–25 (pages unavailable). (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [29] J Schiller, 2012, A review of clinical trials of human papillomavirus prophylactic vaccines, Vaccine source

      The citation is attached to the 93% vaccine-efficacy figure, not to the citing authors’ calculation of 11.6%. Section 4.3 reports 92.4% efficacy against persistent HPV16/18 infection in a vaccine-type-naïve cohort, but does not establish 93% efficacy for the stated 20–25-year-old group; section 4.2 reports 93.2% for a different endpoint, CIN3. The review does not report the calculated 11.6% incidence. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Study design and conductcitation

    The Markov model was based on previously published and validated models for cervical cancer.

    “Based on the previously published and validated models for cervical cancer, we developed a markov model on MS Excel spread sheet, considering the natural history of HPV infection and cervical cancer (Fig 1). [12–15]”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [12] JJ Kim, 2007, Multiparameter calibration of a natural history model of cervical cancer, Am J Epidemiol source
    • cites [13] N Praditsitthikorn, 2011, Economic evaluation of policy options for prevention and control of cervical cancer, Thailand. Pharmacoeconomics source
    • cites [14] G Sroczynski, 2011, Cost-effectiveness of primary HPV screening for cervical cancer in Germany—a decision analysis, Eur J Cancer source
    • cites [15] R Legood, 2006, Lifetime effects, costs, and cost effectiveness of testing for human papillomavirus to manage low grade cytological abnormalities: results of the NHS pilot studies, BMJ source
  • Study design and conductreasoning

    Due to lack of Indian specific data on incidence of HPV infection, age specific HPV incidence rates were derived based on data of HPV infection in a vaccinated cohort of adolescent girls.

    “Similarly, due to lack of Indian specific data on incidence of HPV infection, age specific HPV incidence rates were derived based on data of HPV infection in a vaccinated cohort of adolescent girls. [28]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [28] R Sankaranarayanan, 2016, Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study, Lancet Oncol source
  • Premisecitation

    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]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [47] M Diaz, 2008, Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India, Br J Cancer source

      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
  • May combine two claims. 21
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Study design and conductcitation

    Sensitivity and specificity of each screening strategy and colposcopy, and efficacy of HPV vaccine, were based on published meta-analysis studies.

    “Sensitivity and specificity of each of the screening strategy and colposcopy and efficacy of HPV vaccine was based on the published meta-analysis studies (Table 1). [29, 33, 34]”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [29] J Schiller, 2012, A review of clinical trials of human papillomavirus prophylactic vaccines, Vaccine source

      Section 4.1 reports HPV vaccine efficacy estimates from clinical trials, supporting the vaccine-efficacy part of the sentence. The paper does not provide sensitivity or specificity estimates for screening strategies or colposcopy, and its vaccine efficacy estimates are presented as trial findings rather than as results of a meta-analysis. Page numbers are unavailable in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [33] S Bobdey, 2016, Burden of cervical cancer and role of screening, India. Indian J Med Paediatr Oncol source

      The Results section (page unavailable) reports pooled sensitivity and specificity for several cervical screening methods, based on Indian studies. It does not provide sensitivity or specificity for colposcopy or efficacy estimates for HPV vaccination, and it describes its evidence as a review of studies rather than published meta-analyses. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [34] RA Mustafa, 2016, Systematic reviews and meta-analyses of the accuracy of HPV tests, visual inspection with acetic acid, cytology, and colposcopy, Int J Gynaecol Obstet source

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

    Findingcitation

    Our finding regarding the cost effectiveness of HPV vaccination is in line with a previous analysis done for Punjab state in India.

    “Finally, our finding regarding the cost effectiveness of HPV vaccination are in line with a previous analysis done for Punjab state in India. [35]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [35] S Prinja, 2017, Cost-effectiveness of human papillomavirus vaccination for adolescent girls in Punjab state: Implications for India’s universal immunization program, Cancer source

  • May combine two claims.

    Study design and conductown data

    While estimating the cost of cancer treatment, both the health system cost as well as OOP expenditure was estimated following standard methodologies and based on data collected from one of the largest tertiary care public sector hospital located in India.

    “While estimating the cost of cancer treatment, both the health system cost as well as OOP expenditure was estimated following standard methodologies [37, 40, 50] and based on data collected from one of the largest tertiary care public sector hospital located in India.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [37] MK Chapko, 2009, Equivalence of two healthcare costing methods: bottom-up and top-down, Health Econ source
    • cites [40] ME Drummond, 1987

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

    • cites [50] DP Rice, 2000, Cost of illness studies: What is good about them?, Inj Prev source

      In “Dorothy P Rice” (page unavailable), Rice describes cost-of-illness methods that separate direct costs and disaggregate medical costs by source of payment. This supports the general methodological citation, but the paper does not specify a method for jointly estimating health-system costs and out-of-pocket expenditure for cancer treatment. The hospital data are the citing authors’ own description, not a claim attributed to Rice. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    A systematic review of economic evaluations on cervical cancer screening conducted across low and middle income countries (LMIC) concluded that VIA or HPV are the most efficient alternatives for screening and cytology based screening was shown to be the least effective and more costly screening method.

    “A systematic review of economic evaluations on cervical cancer screening conducted across low and middle income countries (LMIC), also concluded that VIA or HPV are the most efficient alternatives for screening and cytology based screening was shown to be the least effective and more costly screening method. [49]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [49] AK Mezei, 2017, Cost-effectiveness of cervical cancer screening methods in low- and middle-income countries: A systematic review, Int J Cancer source

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

    Premisecitation

    These estimates have also been used to parameterize models to evaluate cervical cancer prevention strategies in Thailand, United Kingdom and Germany.

    “These estimates have also been used to parameterize models to evaluate cervical cancer prevention strategies in Thailand, United Kingdom and Germany. [13–15]”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [13] N Praditsitthikorn, 2011, Economic evaluation of policy options for prevention and control of cervical cancer, Thailand. Pharmacoeconomics source
    • cites [14] G Sroczynski, 2011, Cost-effectiveness of primary HPV screening for cervical cancer in Germany—a decision analysis, Eur J Cancer source
    • cites [15] R Legood, 2006, Lifetime effects, costs, and cost effectiveness of testing for human papillomavirus to manage low grade cytological abnormalities: results of the NHS pilot studies, BMJ source

  • May combine two claims.

    Premisecitation

    Prevention measures in the form of screening and vaccination are effective as well as cost-effective in reducing the burden of cervical cancer, as shown by experience from developed countries.

    “Experience from developed countries has shown that prevention measures in the form of screening and vaccination is effective as well as cost-effective in reducing the burden of cervical cancer. [5]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [5] A Jemal, 2010, Global patterns of cancer incidence and mortality rates and trends, Cancer Epidemiol Biomarkers Prev source

      The Cervix uteri section reports that cervical cancer rates fell by as much as 65% in several Western countries with long-established screening programs. It describes HPV vaccination as an opportunity to reduce the future burden, not as a demonstrated result of developed-country experience. It calls some screening methods affordable but does not establish that screening and vaccination are both cost-effective; it notes the vaccine’s high cost. Page numbers were not provided in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingreasoning

    When the vaccinated cohort of adolescent girls is also screened later in life with VIA every 10 years and VIA every 5 years, cancer cases are reduced by 69%-76% and cancer deaths by 71%-81%.

    “Moreover, when this vaccinated cohort of adolescent girls is also screened later in their life (with VIA every 10 years and VIA 5 years), it leads to 69%-76% reduction in cancer cases and 71%-81% reduction in cancer deaths.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The utility of HPV vaccination in the model is based on its efficacy in providing immunity to HPV infection.

  • May combine two claims.

    Findingown data

    VIA every 10 years was the cheapest screening strategy, while HPV DNA every 3 years was the costliest.

    “The implementation of VIA every 10 years was cheapest strategy, while use of HPV DNA every 3 years was the costliest strategy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among the non-dominated strategies, VIA every 5 years was the most cost-effective strategy (below GDP per capita of US$ 1890 in 2016-17 for India) with maximum health gains at an incremental cost of US$ 829 (INR 54,881) per QALY gained.

    “Finally, among the non-dominated strategies, VIA every 5 years was found to be the most cost-effective strategy (below GDP per capita of US$ 1890 in the year 2016–17 for India) with maximum health gains at an incremental cost of US$ 829 (INR 54,881) per QALY gained.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Screening with VIA every 5 years and VIA every 10 years are cost effective at 1-time per capita GDP.

    “Among various screening strategies, screening with both VIA 5 yearly and VIA 10 yearly came out to be cost effective at 1-time per capita GDP, with VIA every 5 years providing greater health benefits as compared to VIA 10 years.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Compared with no vaccination and no screening, HPV vaccination alone and vaccination plus screening with VIA every 5 or 10 years are cost effective with ICERs ranging from US$86 (INR 5,693) to US$476 (INR 31,511) per QALY gained.

    “As compared to no vaccination and no screening, both HPV vaccination alone and vaccination plus screening (with VIA every 5 yearly and VIA 10 yearly) appears to be cost effective with ICERs in the range of US$ 86 (INR 5,693) to US$ 476 (INR 31,511) per QALY gained.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The utility of HPV vaccination in the model is based on its efficacy in providing immunity to HPV infection.

  • May combine two claims.

    Findingown data

    Screening the same cohort with VIA every 10 years led to 69% reduction in cancer cases and 71% reduction in cancer deaths.

    “In contrast, screening the same cohort with VIA every 10 years led to 69% reduction in cancer cases and 71% reduction in cancer deaths.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Upon screening with VIA, cytology and HPV DNA every 10 years, we estimated a mean cancer reduction of 26%, 23% and 30% respectively.

    “Upon screening with VIA, cytology and HPV DNA every 10 years, we estimated a mean cancer reduction of 26%, 23% and 30% respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared to vaccination plus screening with VIA every 10 years, the strategy of vaccination plus screening with VIA every 5 years results in an incremental cost of US$ 1,986 (956-4,417) per QALY gained, which is more than the cost-effectiveness threshold equal to GDP per capita for India.

    “Analysis of extended dominance reflects that as compared to vaccination plus screening with VIA every 10 years, the strategy of vaccination plus screening with VIA every 5 years results in an incremental cost of US$ 1,986 (956–4,417) per QALY gained, which is more than the cost- effectiveness threshold equals to GDP per capita for India.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Primary data was collected for assessing per person cost of screening, cost of treating cervical cancer and quality of life.

    “Primary data was collected for assessing per person cost of screening, cost of treating cervical cancer and quality of life.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Health-related quality of life was assessed using the EQ-5D-5L tool in 223 cervical cancer patients.

    “A total of 223 cervical cancer patients were recruited from the radiotherapy department of a tertiary care hospital in north India for assessing the health related quality of life (HRQoL) using standard EQ-5D-5L tool.”
    Quote in the paperSubstantial claim

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

    Study design and conductcitation

    The study undertook multivariate probabilistic sensitivity analysis to account for joint parameter uncertainty.

    “To test the uncertainty in the parameter values, we undertook multivariate probabilistic sensitivity analysis (PSA) to account for joint parameter uncertainty. [39]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] P Doubilet, 1985, Probabilistic sensitivity analysis using Monte Carlo simulation. A practical approach, Med Decis Making source

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Out-of-pocket expenditure for cervical cancer treatment was elicited by interviewing a sample of 237 patients.

    “In addition, OOP expenditure incurred by the patients on various therapeutic interventions was elicited by interviewing a sample of 237 patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    Diagnostic accuracy of screening strategies, efficacy of HPV vaccination, and transition probabilities were based on existing meta-analyses.

    “Diagnostic accuracy of the screening strategies, efficacy of HPV vaccination and data on transition probabilities was based on the results of the existing meta-analyses.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Based on data from cancer registries of India, IARC has reported a cumulative lifetime risk of developing cervical cancer in India as 2.40%.

    “Based on the data from cancer registries of India, International Agency for Research on Cancer (IARC) has reported a cumulative lifetime risk (%) of developing cervical cancer in India as 2.40%. [21]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Bruni L, Barrionuevo-Rosas L, Albero G, et al. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in India. Summary Report 27 July 2017.

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

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Our cost analysis captures the realistic programmatic guidelines of NPCDCS program.

    “Our cost analysis captures the realistic programmatic guidelines of NPCDCS program.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Another strength of our study was the use of local data on the cost of screening, treatment of cervical cancer and HRQoL valuation.

    “Another strength of our study was the use of local data on the cost of screening, treatment of cervical cancer and HRQoL valuation.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    Both these derived estimates could have affected the valuation of health outcomes.

    “Both these derived estimates could have affected the valuation of health outcomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    VIA performed at the frequency of every five years yields the best value for money and hence is the most cost-effective strategy as compared to both Pap smear and HPV DNA test.

    “Our study concluded that VIA performed at the frequency of every five years yields the best value for money and hence is most cost-effective strategy as compared to both Pap smear and HPV DNA test.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    One reason for the discrepancy in cost estimates might be due to the non-inclusion of cost pertaining to information, education and communication (IEC) activities in these previous studies.

    “One reason for this discrepancy might be due to the non-inclusion of cost pertaining to information, education and communication (IEC) activities in these previous studies.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    We improved the present analysis compared to the previous publication by adapting the model structure using long term mortality data from India, and by collecting primary data for estimating cost of treatment and quality of life valuation.

    “We improved the present analysis as compare to the previous publication by adapting the model structure using long term mortality data from India. Moreover, primary data was collected for estimating cost of treatment and quality of life valuation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Among various screening strategies, screening with both VIA 5 yearly and VIA 10 yearly is cost effective at 1-time per capita GDP, with VIA every 5 years providing greater health benefits as compared to VIA 10 years.

    “Among various screening strategies, screening with both VIA 5 yearly and VIA 10 yearly is cost effective at 1-time per capita GDP, with VIA every 5 years providing greater health benefits as compared to VIA 10 years.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The national cancer registry program generates estimates on the incidence of cancer cases in India.

    “However, the national cancer registry program generates estimates on the incidence of cancer cases in India. [21]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Bruni L, Barrionuevo-Rosas L, Albero G, et al. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in India. Summary Report 27 July 2017.

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

  • May combine two claims.

    Interpretationown data

    While the analysis would be more robust if non-high risk HPV variants are also included, the results of the present analysis in terms of their conclusion about VIA 5 years being most cost effective is valid.

    “Hence, we believe that while the analysis would be more robust, if non high risk HPV variants are also included in the study, however, the results of present analysis in terms of their conclusion about VIA 5 years being most cost effective is valid.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Since several non-high risk precancerous lesions may not progress to develop cancer, it is likely to result in an increase in false-positives, which will increase the cost of screening and hence increase the ICER value.

    “However, since several of these non-high risk precancerous lesions may not progress of develop cancer, it is likely to result in an increase in false-positives, which will increase the cost of screening and hence increase the ICER value.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Our model accounts for 85% of the benefits due to the second and the third reason mentioned above, but it doesn't capture the benefits resulting from a vaccinated woman having non-HPV 16/18 cancers detected.

    “Although our model accounts for 85% of the benefits due to the second and the third reason mentioned above, it doesn’t capture the benefits resulting from a vaccinated woman having non- HPV 16/18 cancers detected.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    In the policy of vaccination and screening combined, the additional benefit of screening besides vaccination accrues because of three reasons: vaccinated women would benefit from getting non-HPV 16/18 cancers detected; unvaccinated women would benefit from getting all cervical cancers detected; and vaccinated women on whom vaccine proved inefficacious (7%) would benefit from all cancer getting dét

    “In case of the policy of vaccination and screening combined, the additional benefit of screening besides vaccination are accrued because of three reasons, firstly, vaccinated women would benefit from getting non- HPV 16/18 cancers detected, secondly, unvaccinated women would benefit from getting all cervical cancers detected, and thirdly, vaccinated women on which vaccine proved inefficacious (7%)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Although this underestimation is likely to improve the ICER value for the policy of vaccination and screening combined, the exact effect is not straightforward, as factors like additional cost of diagnostic tests (colposcopy, biopsy etc.), averted cost of cancer treatment, and QALYs contributed by these prevented cases will play an important role in determining the ICER.

    “Although this underestimation is likely to improve the ICER value for the policy of vaccination and screening combined, yet the exact effect is not straightforward, as factors like additional cost of diagnostic tests (colposcopy, biopsy etc.), averted cost of cancer treatment, and QALYs contributed by these prevented cases will play an important role in determining the ICER.”
    Quote in the paperNot a substantial claim
33 of 33

  • The authors state this as an assumption.

    Invasive cervical cancer is treated according to India’s National Cancer Grid Guidelines.

    “The invasive cancer was assumed to be treated according to the India’s National Cancer Grid Guidelines for the treatment of invasive cervical cancer. [23, 24]”

  • The authors state this as an assumption.

    Precancerous lesions are treated as per standard guidelines with cryotherapy, loop electrosurgical excision procedure, or surgery depending on the spread of the lesion.

    “Similarly, the precancerous lesions were assumed to be treated as per standard guidelines i.e., with cryotherapy, loop electrosurgical excision procedure (LEEP) or surgery depending upon the spread of the lesion (S1 File of S1 Table). [9, 22, 25]”

  • The authors state this as an assumption.

    Women treated for precancerous lesions are considered treated for HPV infection and return to the healthy state, but remain at risk for future disease based on age-specific incidence of HPV infection.

    “Women treated for precancerous lesions were considered treated for HPV infection and were assumed to return to the healthy state, but were still at risk for future disease based on the age specific incidence of HPV infection.”

  • The authors state this as an assumption.

    The sensitivity of diagnosing stage 1 cancer is the same as that of precancerous states, and sensitivity is 100% for diagnosing women in stage 2 to stage 4 invasive cancer.

    “While the sensitivity of diagnosing stage 1 of the cancer was assumed to be same as that of the precancerous states, the sensitivity was assumed to be 100% for diagnosing women in stage 2 to stage 4 of invasive cancer.”

  • The authors state this as an assumption.

    Biopsy always results in the diagnosis of the true health state.

    “It was also assumed that the biopsy always resulted in the diagnosis of true health state.”

  • The authors state this as an assumption.

    Health-related quality of life stabilizes after 4–5 months following treatment, so patients who completed at least 4 months post-treatment were eligible.

    “Based on the consultation with the oncologists, it was assumed that HRQoL tends to get stabilized after 4–5 months following treatment. Thus, those patients who had completed at least 4 months post treatment for cervical cancer were considered eligible and were interviewed at the time of their follow-up visit in the outpatient clinic of radiotherapy department.”

  • The authors state this as an assumption.

    Patients in undiagnosed cervical carcinoma can die due to cancer only after progressing through all stages of the cancer and within the first year of moving into stage 4.

    “It was assumed that patients in undiagnosed cervical carcinoma can die due to cancer, only after progressing through all the stages of the cancer (as per natural history of the cervical cancer) and within the first year of moving into the stage 4.”

  • The authors state this as an assumption.

    The utility of HPV vaccination in the model is based on its efficacy in providing immunity to HPV infection.

    “Further, the utility of vaccination was based on its efficacy in providing immunity to the HPV infection.”

  • The paper relies on this without support.

    Limited availability of infrastructure and trained manpower in India poses financial and health system feasibility challenges for implementing preventive interventions.

    “But limited availability of infrastructure and trained manpower in developing country like India, poses both financial challenge as well as the issue of health system feasibility in implementing these preventive interventions.”

  • The paper relies on this without support.

    The natural progression of disease is not expected to vary by region.

    “Moreover, since the natural progression of disease is not expected to vary by region, these estimates were considered appropriate.”

  • The paper relies on this without support.

    IEC activities play an instrumental role in the success of a screening program, especially when launched for the first time on a countrywide basis.

    “As IEC activities play an instrumental role in success of a screening program, especially when the program is thought to be launched for the first time on a countrywide basis, it is has to be essentially included in the calculation of overall cost.”

  • The paper relies on this without support.

    There is no systematic recording of incidence of precancerous lesions in India.

    “There is no systematic recording of incidence of precancerous lesions.”

  • The paper relies on this without support.

    Incidence estimates for HPV infection other than HPV 16 & 18 are not present.

    “Similarly, while the data on incidence of HPV 16 & 18 infection is available, the incidence estimates for other HPV infection is not present.”
13 of 13

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Five-year VIA screening has two different ICERs

    Major

    The discussion gives US$476 per QALY for VIA screening every five years, whereas the abstract and cost-effectiveness results give US$829 for that strategy. US$476 is reported for a different strategy: vaccination combined with five-year VIA screening.

  • Pap smear screening-cost lower bound has inconsistent currency conversion

    Minor

    Using the stated conversion rate of 66.2 INR per US$, the lower bound of INR 289 million is US$4.37 million, not the reported US$3.36 million.

    Reported 3.36 · recomputed 4.365559

  • ICERs for vaccination plus five- and ten-year screening are reversed

    Minor

    The prose assigns US$402 to five-year screening and US$476 to ten-year screening, respectively. Table 5 assigns US$476 to five-year screening and US$402 to ten-year screening.

  • HPV DNA three-year total-cost upper bound has inconsistent currency conversion

    Minor

    At the stated conversion rate, the upper bound of INR 1,849 million is US$27.93 million, not the reported US$22.50 million.

    Reported 22.5 · recomputed 27.930514

4 of 4

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Chauhan, A. S., Prinja, S., Srinivasan, R., Rai, B., Malliga, J., Jyani, G., Gupta, N., & Ghoshal, S.
Affiliations
  • Post Graduate Institute of Medical Education and Research (IN)
  • Cancer Institute (WIA) (IN)
  • Government Medical College and Hospital (IN)
Corresponding author
Prinja, Shankar
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2020-09-01
Volume
15
Issue
9
Pages
e0238291
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0238291
PMC
PMC7462298
OpenAlex
W3081739328
Cited by
75
References
41
Citations by year
2026: 10 · 2025: 9 · 2024: 19 · 2023: 9 · 2022: 14 · 2021: 10 · 2020: 4
FWCI
5.68
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Greater South Information System
Funders
Department of Health Research, India (T 11011/02/2017-HR)
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Health Systems, Economic Evaluations, Quality of Life
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Women's cancer prevention and management
Keywords
cervical cancer prevention, cost-effectiveness, HPV vaccination, visual inspection with acetic acid, Pap smear, HPV testing, cervical cancer screening, HPV 16/18, adolescent girls, Markov model, quality-adjusted life years, India, cervical cancer mortality, screening frequency, societal perspective, quality of life
MeSH terms
Adult, Aged, Uterine Cervical Neoplasms, Cost-Benefit Analysis, DNA, Viral, Female, Humans, India, Markov Chains, Mass Screening, Middle Aged, Quality of Life, Vaccination, Papillomavirus Infections, Human papillomavirus 18, Human papillomavirus 16, Young Adult, Papanicolaou Test

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.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review