Building resilient cervical cancer prevention through gender-neutral HPV vaccination

  1. Irene Man
  2. Damien Georges
  3. Rengaswamy Sankaranarayanan
  4. Partha Basu
  5. Iacopo Baussano

  • Curated by eLife

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    eLife assessment

    This study presents valuable findings on how gender-neutral vaccination against human papillomavirus can help improve program resilience in the case of vaccination disruptions. The evidence supporting the claims of the authors is convincing, although the results are only applicable to India and other countries with a similar HPV context; researchers can adapt the model for their local context and use it as a starting point for future research.

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Abstract

The COVID-19 pandemic has disrupted HPV vaccination programmes worldwide. Using an agent-based model, EpiMetHeos, recently calibrated to Indian data, we illustrate how shifting from a girls-only (GO) to a gender-neutral (GN) vaccination strategy could improve the resilience of cervical cancer prevention against disruption of HPV vaccination. In the base case of 5-year disruption with no coverage, shifting from GO to GN strategy under 60% coverage (before disruption) would increase the resilience, in terms of cervical cancer cases still prevented in the disrupted birth cohorts per 100,000 girls born, by 2.8-fold from 107 to 302 cases, and by 2.2-fold from 209 to 464 cases under 90% coverage. Furthermore, shifting to GN vaccination helped in reaching the World Health Organization (WHO) elimination threshold. Under GO vaccination with 60% coverage, the age-standardised incidence rate of cervical cancer in India in the long term with vaccination decreased from 11.0 to 4.7 cases per 100,000 woman-years (above threshold), as compared to 2.8 cases (below threshold) under GN with 60% coverage and 2.4 cases (below threshold) under GN with 90% coverage. In conclusion, GN HPV vaccination is an effective strategy to improve the resilience to disruption of cancer prevention programmes and to enhance the progress towards cervical cancer elimination.

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  1. Version published to 10.7554/elife.85735 on eLife
  2. eLife

    Author Response

    Reviewer #1 (Public Review):

    The sustainability of vaccination programs is subject to multiple threats, from a pandemic like COVID-19 to political changes. The present study assesses different strategies, including gender-neutral vaccination, to better respond to threats in HPV national immunization programs. The authors showed that vaccinating boys against HPV (compared to vaccinating girls alone), would not only prevent more cases of cervical cancer but also limit the impact of disruptions in the program. Moreover, it would help attain the goal set by the World Health Organization of eliminating cervical cancer as a public health problem sooner, even in the case of disruptions.

    Strengths and weaknesses: I found the manuscript well-written and easy to read. Decision-makers may find the results helpful in policy development and other researchers may use the study as an example to investigate similar scenarios in their local contexts. Nevertheless, there are some limitations. First, it should be considered that the present study is only applicable to India and other countries with a similar HPV context. Second, because it is a study based on a mathematical model, errors might arise from the assumptions considered for its construction. It also relies on the quality of the data used to construct and calibrate the model.

    Models are important tools for decision-making, they allow us to assess different scenarios when obtaining real-world data is not feasible. They also allow to carried-out multiple sensitivity analyses to test the strengths of the results. The study carries out a necessary assessment of different vaccination strategies to minimize the impact on cervical cancer prevention due to disruptions in the HPV immunization program. By using a mathematical model, the authors are able to assess different scenarios regarding vaccination coverage rates, disruption time, and cervical cancer incidence. Therefore, decision-makers can consider the scenario which best represents their current situation.

    The present study is not only valuable for decision-making, but also from a methodological point of view as future research can be conducted exploring more in deep the impact of vaccination disruptions and prevention measures.

    The conclusions of this paper are mostly well supported by data, but some aspects of the methodology need clarification; furthermore, some aspects of the calculations can be improved. It would be more informative, and better for comparisons between the four scenarios, to have relative measures instead of the absolute numbers of cases prevented.

    We thank the reviewer for the kind acknowledgement of the merits of the paper. We have tried to address the suggestions and questions as much as possible in the revised manuscript.

    We agree to the points of weaknesses raised by the reviewer regarding the applicability of our study results is limited to other countries and the possible errors arising from a using a mathematical model. We have added more elaborate discussion of these points in the manuscript, as follows: - Page 15 lines 310-312: “Extrapolation of the results of this study to other populations will be limited to those sharing similar patterns of demography, social norms, and cervical cancer epidemiology as India.”

    • Page 17 lines 361-363: “…, within the limitations of our model, the modelbased estimates show that shifting from GO to GN vaccination may improve the resilience of the Indian HPV vaccination programme while also enhancing progress towards the elimination of cervical cancer.”

    Furthermore, we have tried to clarify the rationale, advantages, and limitations of the measure of resilience we have adopted.

    Reviewer #2 (Public Review):

    This study evaluated the effect of population-based HPV vaccination programs in India which is suffering from the disease burden of cervical cancer. The authors used model simulations for estimating the outcomes by adopting the latest available data in the literature. The findings provide evidence-based support for policymakers to devise efficient strategies to reduce the impacts of cervical cancer in the country.

    Strengths.

    The study investigated the potential impact of cervical cancer elimination when HPV vaccination was disrupted (e.g., during the COVID-19 pandemic) and for meeting the WHO's initiatives. The authors considered several settings from the low to high effects of vaccination disruption when concluding the findings. The natural history was calibrated to local-specific epidemiological data which helps highlight the validity of the estimation.

    Weaknesses.

    Despite the importance and strengths, the current study may likely be improved in several directions. First, the study considered the scenario of using a recently developed domestic HPV vaccine but assuming vaccine efficacy based on another foreign HPV vaccine that has been developed and used (overseas) for more than 10 years. More information should be provided to support this important setting.

    Second, the authors are advised to discuss the vaccine acceptability and particularly the feasibility to achieve high coverage scenarios in relatively conservative countries where HPV vaccines aim to prevent sexually transmitted infection. Third, as the authors highlighted, the health economics of gender-neutral strategies, which is currently missing in the manuscript, would be a substantial consideration for policymakers to implement a national, population-based vaccination program.

    We thank the reviewer for the kind acknowledgement of the merits and strengths of the paper.

    We have tried to address the reviewer’s three points of weaknesses as comprehensively as possible in the revised manuscript.

    Regarding the first two points of weaknesses, we have provided more background information about the current situation of HPV introduction and screening in India (see the more specific replies below for where changes have been made), and some data of observed coverage in India in the states where HPV vaccination has been introduced.

    Regarding the reviewer’s third point about the health economics of genderneutral strategies, we agree fully that it is an important aspect to consider for the local policymakers. However, a health economic assessment is out of the scope of the present paper. In the present paper, we are interested in highlighting the potential health benefits on GN HPV vaccination. Given the current context of HPV vaccination in India we think it is too early to provide a realistic assessment of the health-economic balance of GN vaccination. Please note that one manuscript (de Carvalho et al., MedRxiv, doi: https://doi.org/10.1101/2023.04.14.23288563) based on the same modelling exercise and reporting a health economic assessment of girls-only (routine and catch-up) HPV vaccination in India is currently submitted for peer-review.

    Reviewer #3 (Public Review):

    The authors put together a rigorous study to model the impact of HPV vaccine programme disruptions on cervical cancer incidence and meeting WHO elimination goals in a low-income country - using India as an example. The study explores possible scenarios by varying HPV vaccination strategies for 10-year-old children between a) increasing vaccine coverage in a girls-only vaccination programme and b) vaccinating boys in addition to girls (i.e a gender-neutral vaccination programme).

    The main strength of this study is the strength of the modelling methodology in helping to make predictions and in contingency planning. The study methodology is rigorous and uses models that have been validated in other settings. The study employs a high level of detail in calibrating and adapting the model to the Indian context despite poor data availability. The detailed methodology allows future studies to employ the model and techniques with locally-contextualised parameters to study the potential impact of HPV vaccine programme disruptions in other countries.

    The work in this field can begin to help lower-income countries explore varying HPV vaccination strategies to reduce cervical cancer incidence, keeping in mind the potential for future supply chains or other related disruptions. However, the scenarios could be better sculpted to model potentially realistic scenarios to guide policymakers to make decisions in situations with limited vaccine supplies - in other words comparing scenario alternatives based on a fixed number of vaccines being available. Using comparative alternatives will help policymakers grapple with the decisions that need to be made regarding planning national HPV vaccination programmes. The results could afford to provide readers with a clearer measure of vaccine strategy 'resilience'.

    In all, the authors are able to successfully explore the potential impact of varying HPV vaccination strategies on cervical cancer cases prevented in the context of vaccine disruptions, and make valid conclusions. The results produced are rich in information and are worthy of deeper discussion.

    We thank the reviewer for the kind acknowledgement of the merits and strengths of the paper.

  3. eLife

    eLife assessment

    This study presents valuable findings on how gender-neutral vaccination against human papillomavirus can help improve program resilience in the case of vaccination disruptions. The evidence supporting the claims of the authors is convincing, although the results are only applicable to India and other countries with a similar HPV context; researchers can adapt the model for their local context and use it as a starting point for future research.

  4. eLife

    Reviewer #1 (Public Review):

    The sustainability of vaccination programs is subject to multiple threats, from a pandemic like COVID-19 to political changes. The present study assesses different strategies, including gender-neutral vaccination, to better respond to threats in HPV national immunization programs. The authors showed that vaccinating boys against HPV (compared to vaccinating girls alone), would not only prevent more cases of cervical cancer but also limit the impact of disruptions in the program. Moreover, it would help attain the goal set by the World Health Organization of eliminating cervical cancer as a public health problem sooner, even in the case of disruptions.

    Strengths and weaknesses: I found the manuscript well-written and easy to read. Decision-makers may find the results helpful in policy development and other researchers may use the study as an example to investigate similar scenarios in their local contexts. Nevertheless, there are some limitations. First, it should be considered that the present study is only applicable to India and other countries with a similar HPV context. Second, because it is a study based on a mathematical model, errors might arise from the assumptions considered for its construction. It also relies on the quality of the data used to construct and calibrate the model.

    Models are important tools for decision-making, they allow us to assess different scenarios when obtaining real-world data is not feasible. They also allow to carried-out multiple sensitivity analyses to test the strengths of the results. The study carries out a necessary assessment of different vaccination strategies to minimize the impact on cervical cancer prevention due to disruptions in the HPV immunization program. By using a mathematical model, the authors are able to assess different scenarios regarding vaccination coverage rates, disruption time, and cervical cancer incidence. Therefore, decision-makers can consider the scenario which best represents their current situation.

    The present study is not only valuable for decision-making, but also from a methodological point of view as future research can be conducted exploring more in deep the impact of vaccination disruptions and prevention measures.

    The conclusions of this paper are mostly well supported by data, but some aspects of the methodology need clarification; furthermore, some aspects of the calculations can be improved. It would be more informative, and better for comparisons between the four scenarios, to have relative measures instead of the absolute numbers of cases prevented.

  5. eLife

    Reviewer #2 (Public Review):

    This study evaluated the effect of population-based HPV vaccination programs in India which is suffering from the disease burden of cervical cancer. The authors used model simulations for estimating the outcomes by adopting the latest available data in the literature. The findings provide evidence-based support for policymakers to devise efficient strategies to reduce the impacts of cervical cancer in the country.

    Strengths.
    The study investigated the potential impact of cervical cancer elimination when HPV vaccination was disrupted (e.g., during the COVID-19 pandemic) and for meeting the WHO's initiatives. The authors considered several settings from the low to high effects of vaccination disruption when concluding the findings. The natural history was calibrated to local-specific epidemiological data which helps highlight the validity of the estimation.

    Weaknesses.
    Despite the importance and strengths, the current study may likely be improved in several directions. First, the study considered the scenario of using a recently developed domestic HPV vaccine but assuming vaccine efficacy based on another foreign HPV vaccine that has been developed and used (overseas) for more than 10 years. More information should be provided to support this important setting.

    Second, the authors are advised to discuss the vaccine acceptability and particularly the feasibility to achieve high coverage scenarios in relatively conservative countries where HPV vaccines aim to prevent sexually transmitted infection. Third, as the authors highlighted, the health economics of gender-neutral strategies, which is currently missing in the manuscript, would be a substantial consideration for policymakers to implement a national, population-based vaccination program.

  6. eLife

    Reviewer #3 (Public Review):

    The authors put together a rigorous study to model the impact of HPV vaccine programme disruptions on cervical cancer incidence and meeting WHO elimination goals in a low-income country - using India as an example. The study explores possible scenarios by varying HPV vaccination strategies for 10-year-old children between a) increasing vaccine coverage in a girls-only vaccination programme and b) vaccinating boys in addition to girls (i.e a gender-neutral vaccination programme).

    The main strength of this study is the strength of the modelling methodology in helping to make predictions and in contingency planning. The study methodology is rigorous and uses models that have been validated in other settings. The study employs a high level of detail in calibrating and adapting the model to the Indian context despite poor data availability. The detailed methodology allows future studies to employ the model and techniques with locally-contextualised parameters to study the potential impact of HPV vaccine programme disruptions in other countries.

    The work in this field can begin to help lower-income countries explore varying HPV vaccination strategies to reduce cervical cancer incidence, keeping in mind the potential for future supply chains or other related disruptions. However, the scenarios could be better sculpted to model potentially realistic scenarios to guide policymakers to make decisions in situations with limited vaccine supplies - in other words comparing scenario alternatives based on a fixed number of vaccines being available. Using comparative alternatives will help policymakers grapple with the decisions that need to be made regarding planning national HPV vaccination programmes. The results could afford to provide readers with a clearer measure of vaccine strategy 'resilience'.

    In all, the authors are able to successfully explore the potential impact of varying HPV vaccination strategies on cervical cancer cases prevented in the context of vaccine disruptions, and make valid conclusions. The results produced are rich in information and are worthy of deeper discussion.

  7. Version published to 10.1101/2023.01.17.23284655v1 on medRxiv