High-risk human papillomavirus prevalence among South African women diagnosed with other STIs and BV

Wenkosi Qulu; Andile Mtshali; Farzana Osman; Nonsikelelo Ndlela; Lungelo Ntuli; Gugulethu Mzobe; Nivashnee Naicker; Nigel Garrett; Anne Rompalo; Adrian Mindel; Sinaye Ngcapu; Lenine Liebenberg

doi:10.1371/journal.pone.0294698

Peer Review History

Original SubmissionAugust 8, 2023
20 Oct 2023 Decision Letter - Nontuthuzelo Iris Muriel Somdyala, Editor PONE-D-23-24791High-risk human papillomavirus prevalence among South African women diagnosed with other STIs and BVPLOS ONE Dear Dr. Liebenberg, 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 a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Dec 04 2023 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. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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AM is funded by DST/NRF Innovation Postdoctoral Fellowship grant number: PDG210309589501. GM is funded by DST/NRF Innovation Postdoctoral Fellowship grant number: SFP180507326699. Poliomyelitis Research Foundation (PRF grant number: 18/16).” Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. 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Revision 1
27 Oct 2023 Author Response Response to reviewers Reviewer #1 1. The study is well conceptualized and accepted. Despite modest numbers, there is valuable information about HPV, STI, and bacterial vaginosis. Perhaps the only area for improvement is the reporting and discussion of the MMP analysis. A slightly more comprehensive justification of the importance of MMP will strengthen the manuscript. Response: The text was updated to provide a more comprehensive support for the importance of investigating the contribution of HPV on mucosal barrier integrity, particularly in this context of high HIV burden. Line 246 – 248: The association between HPV infection and the exact mechanism such as markers of epithelial barrier integrity that may contribute to cervical cancer disease progression remains an active area of research. Line 307-309: In healthy tissue, MMP expression and activity is well coordinated, however, upon HPV infection this regulation is disrupted [60]. Line 314-322: Evidently, increased MMP-10 expression has been associated with resistance to apoptosis and stimulation of pro-angiogenic factors such as hypoxia-inducible factor-1 alpha (HIF)-1α and MMP-2, and pro-metastatic factors including plasminogen activator inhibitor-1 (PAI-1) and chemokine (CXC motif) receptor 2 (CXCR2) [61]. Accordingly, in vivo siRNA therapeutics targeting MMP-10 have demonstrated a reduction in tumour growth and angiogenesis [61]. In summary, the increased expression of MMP-10 in women with STIs and/or BV suggests a potential correlation with the development of cervical intraepithelial lesions. These findings collectively underscore the significance of MMPs as a viable target for therapeutic intervention in HPV-associated cervical cancer. Line: 307 – 309: In healthy tissue, MMP expression and activity is well coordinated, however, upon HPV infection this regulation is disrupted [5]. Line: 314 – 317: In summary, the increased expression of MMP-10 in women with STIs and/or BV denotes the invasive and metastatic characteristics of cervical cancers, emphasizing the importance of MMPs as a potential therapeutic target for intervention in HPV-associated cervical cancer. Additional journal requirements 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Response: We have carefully reviewed the PLOS ONE style guidelines and have made the necessary adjustments to bring the manuscript into compliance with PLOS ONE style requirements. 2. Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." Response: The funders supported either the original cohort development or provided author salary/developmental support but had no involvement in this study. The text was updated to reflect this: The funders had no role in study design, data collection and analysis, decisions related to publication, or preparation of the manuscript. 3. We note that you have indicated that data from this study are available upon request. a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. Response: We comply with CAPRISA’s data-sharing policy for sensitive information and encourage interaction between requesters and study PIs. This connection is facilitated through a portal on the CAPRISA website prior to data sharing. The text is updated to reflect this: “Data will be made available through request on a dedicated portal on the CAPRISA website (https://www.caprisa.org/Pages/CAPRISAStudies)." 4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. Response: The ethics statement has been removed from the acknowledgment section and only appears in the method section of the manuscript 5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. 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. Response: We have revised the following references to enhance the comprehensive scope of the subject and to incorporate the most up-to-date and relevant literature: a) We substituted (Reference 51) Di Pietro, M., et al., HPV/Chlamydia trachomatis co-infection: metagenomic analysis of cervical microbiota in asymptomatic women. New Microbiologica, 2018. 41(1): p. 513 34-41, with (Reference 8) Liebenberg, L.J., et al., HPV infection and the genital cytokine milieu in women at 395 high risk of HIV acquisition. Nature Communications, 2019. 10(1): p. 5227. b) We replaced (Reference 55) Gabster, A., et al., High prevalence of sexually transmitted infections, and high-risk sexual behaviors among Indigenous adolescents of the Comarca Ngäbe-Buglé, Panama. Sexually Transmitted Diseases, 2019. 46(12): p. 780-787. with (Reference 53) Dareng, E.O., et al., Vaginal microbiota diversity and paucity of Lactobacillus species are associated with persistent hrHPV infection in HIV negative but not in HIV positive women. Scientific Reports, 2020. 10(1): p. 19095. c) We replaced: (Reference 57) Castro, J., et al., Using an in-vitro biofilm model to assess the virulence potential of bacterial vaginosis or non-bacterial vaginosis Gardnerella vaginalis isolates. Scientific Reports, 2015. 5(1): p. 1-10. and (Reference 58) Masuzzo, P., et al., An end-to-end software solution for the analysis of high throughput single-cell migration data. Scientific Reports, with (Reference 51) Godoy-Vitorino, F., et al., Cervicovaginal fungi and bacteria associated with cervical intraepithelial neoplasia and high-risk human papillomavirus infections in a hispanic population. Frontiers in microbiology, 2018. 9: p. 2533. and (Reference 55) Berggrund, M., et al., Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2+. Virology journal, 2020. 17: p. 1-9 https://doi.org/10.1371/journal.pone.0294698.r002
7 Nov 2023 Decision Letter - Nontuthuzelo Iris Muriel Somdyala, Editor High-risk human papillomavirus prevalence among South African women diagnosed with other STIs and BV PONE-D-23-24791R1 Dear Dr. Liebenberg, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Nontuthuzelo Iris Muriel Somdyala, Ph.D Academic Editor PLOS ONE Additional Editor Comments (optional): Dear Dr Liebenberg Thank you for your submission of your research to the PLOS ONE Journal. And also, on behalf of the journal I am grateful to the review made on your manuscript to which you responded carefully as advised. After checking all comments, I am satisfied that your manuscript proceeds to publication process in which our capable team will take you through. PLOS ONE Journal values your input to the science knowledge. Reviewers' comments: https://doi.org/10.1371/journal.pone.0294698.r003
Formally Accepted
20 Nov 2023 Acceptance Letter - Nontuthuzelo Iris Muriel Somdyala, Editor PONE-D-23-24791R1 High-risk human papillomavirus prevalence among South African women diagnosed with other STIs and BV Dear Dr. Liebenberg: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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. Nontuthuzelo Iris Muriel Somdyala Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0294698.r004

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