Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: Results from a quasi-experimental pragmatic implementation trial

Anu Mary Oommen; Rita Isaac; Biswajit Paul; David Weller; Madelon L. Finkel; Anitha Thomas; Thomas Samuel Ram; Prashanth H. R.; Anne George Cherian; Vinotha Thomas; Vathsala Sadan; Rajeswari Siva; Anuradha Rose; Tobey Ann Marcus; Shalini Jeyapaul; Sangeetha Rathnam K.; Tabeetha Malini; Surenthiran N.; Paul Jebaraj; Neenu Oliver John; Charles Ramesh; Jeffers Jayachandra Raj C.; Rakesh Kumar S.; Balaji B. V.; Irene Dorathy P.; Valliammal Murali; Prema N.; Kavitha K.; Priya Ranjani D.

doi:10.1371/journal.pone.0301385

Peer Review History

Original SubmissionAugust 10, 2023
11 Jan 2024 Decision Letter - Pijush Kanti Khan, Editor PONE-D-23-25033Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: results from a quasi-experimental pragmatic implementation trialPLOS ONE Dear Dr. Isaac, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit aPlease ensure that your decision is justified on PLOS ONE’s publication criteria and not, for example, on novelty or perceived impact. Please submit your revised manuscript by Feb 25 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: First and foremost I would like to thank you for providing me an opportunity to review this research article which is a piece of outstanding work of implementation research (IR). I am very pleased to inform you that this study will bring an outstanding outcome in terms of screening coverage, treatment and compliance in low resource setting in tribal, rural and slum-urban areas of India which is a very neglected areas of our Indian society. Barriers and issues were very well addressed and explained in context of tribal, rural and slum-urban settings highlighting the challenges in real settings in terms of Indian population. Methodology is very clear and well explained to achieve the target of research question for evaluation of implementation programmes. Framework of IR is well addressing the contextual factors and is found to be feasible, adaptable and scalable to limited resource settings of the present evidence based intervention. Barriers and challenges are very well identified and addressed and programmatic changes were made to implementation strategy for its adoption in the real setting for optimization of HPV test based cervical cancer screening, and its treatment programmes. A profound and robust implementation strategy were adopted to provide large coverage to women population of the study settings. Multi-faceted approach were adopted to increase the accessibility of HPV test, health care provider capacity building, community engagement, counselling of community by self sampling by the healthcare provider and triage process by frontline health care workers (HCWs). After implementation outcome, a significant proportion of compliance to triage process was also reported in the study settings which is a signification solution of applying implementation strategy and translating research into practice. Findings of the present study will contribute a significant outcome of HPV based cervical cancer screening and its treatment programme through IR ensuring its adoption, fidelity, feasibility, adaptability, scalability in terms of women population coverage to maintain the sustainability in the limited resource settings in other states of India as well. Reviewer #2: Thanks for the invitation to review this study. This research evaluates the implementation of HPV test-based cervical cancer screening in rural, urban slum, and tribal areas in India. It employed a pragmatic, quasi-experimental design, focusing on self-collected HPV testing for women aged 30-60. The study found varied screening and triage compliance rates across settings, highlighting the importance of adapting strategies to local contexts. Key challenges included accessibility, cultural barriers, and health system limitations. The study underscores the feasibility and need for context-specific adaptations in cervical cancer screening programs in low-resource settings. The study identifies several limitations. Firstly, its quasi-experimental design limits the ability to establish causality. Secondly, self-reported data may introduce recall bias and affect the reliability of some findings. Thirdly, the study focuses on specific geographic areas in India, which may limit the generalizability of the results to other settings. Additionally, the study does not fully explore the long-term outcomes of the screening program, and the potential impact of socio-cultural factors on screening behaviours is not thoroughly examined. Finally, the study's reliance on existing health infrastructure might overlook the challenges in settings with more limited resources. Adding these items to the limitations section of the manuscript would make it more informative for the audience. Other sections and aspects of the manuscript is well prepared and I have no further comments and suggestions for improvement. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Dr. Anjali Kumari Reviewer #2: Yes: Sina Azadnajafabad, MD, MPH ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0301385.r001
Revision 1
24 Feb 2024 Author Response Response to Reviewers On behalf of all the authors, I want to place on record our sincere thanks to the reviewers for an excellent review and appreciation of our hard work and study methods chosen. We see the reviewers have a good understanding of the implementation science research. We want to thank the editors too for identifying the right people for the review. Response to academic editor’s review • We haven’t made any changes in the financial disclosure. • We do not have any figure in the manuscript. • We have used publicly available, routinely used laboratory tests for this research, so depositing the laboratory protocols in protocol.io is not applicable. • We have followed the PLOS ONE's style requirements while formatting to the best of our ability • We have removed the reference no.21 from the previous submitted version as it is not a published article. It is a reference to data from the existing health information system of the research organisation. We have mentioned that in parenthesis in the text. 21. Health information system, RUHSA. Christian Medical College Vellore. • We have edited the references 4 and 5 to comply with PLOS ONE publication criteria Reviewer’s comments Reviewer 1# We would like to thank the reviewer once again for the excellent review and appreciation of our work and study methods. Reviewer 2# 1. The study identifies several limitations. Firstly, its quasi-experimental design limits the ability to establish causality. As the reviewer has suggested, we have added a few additional lines to explain why a quasi-experimental design was chosen and its merits in 342 to 355 lines. 2. Secondly, self-reported data may introduce recall bias and affect the reliability of some findings. We have mentioned in the methodology section that the study focused on rigorous training of the data collectors to reduce the recall bias. Also the intervention was rolled out only for a short period of 8 months and therefore pre-post intervention qualitative data collected on the barriers and challenges of cancer screening may not be significantly affected by recall bias. As the main outcomes we measured were screening and follow-up rates which were objective measures based on our program data, these are not affected by recall bias. 3. Thirdly, the study focuses on specific geographic areas in India, which may limit the generalizability of the results to other settings. Across all states in India, the society has been broadly divided into tribal, rural and urban societies on the basis of their geographical surroundings and socio-cultural characteristics. We have chosen the 3 resource limited settings within the existing geographic divisions. Though there may be some sociocultural differences in the uptake of interventions across states, the 3 sites largely represent rural, tribal and urban slums, the major geographical divisions in India 4. Additionally, the study does not fully explore the long-term outcomes of the screening program, This study is a short term pragmatic pilot trial. There is a fund approved RCT being planned in the study site which will also measure long term outcomes. 5. the potential impact of socio-cultural factors on screening behaviours is not thoroughly examined. We believe the differences that this study have picked up in 3 diverse societies explain the impact of sociocultural factors. We have also examined these through qualitative studies in the area before and after the intervention, which will be published separately. 6. Finally, the study's reliance on existing health infrastructure might overlook the challenges in settings with more limited resources. We agree with the reviewer that the existing health infrastructure in the study sites would have certainly impacted the outcomes. It will be more challenging to implement this screening programme in more limited settings. 7. Adding these items to the limitations section of the manuscript would make it more informative for the audience. As per the reviewer’s suggestion, we have added a few lines under limitations. Please see the lines 342 to 355. Thank you, Prof. Rita Isaac Corresponding Author Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0301385.r002
14 Mar 2024 Decision Letter - Pijush Kanti Khan, Editor Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: results from a quasi-experimental pragmatic implementation trial PONE-D-23-25033R1 Dear Dr. Isaac, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at http://www.editorialmanager.com/pone/ and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Pijush Kanti Khan, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0301385.r003
Formally Accepted
26 Mar 2024 Acceptance Letter - Pijush Kanti Khan, Editor PONE-D-23-25033R1 PLOS ONE Dear Dr. Isaac, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Pijush Kanti Khan Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0301385.r004

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