A Cross-Sectional Survey on HPV Vaccination in a Houston HIV Clinic

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Although the topic is relevant, the manuscript substantially overlaps with prior reviews and does not provide sufficient original insight; methodological weaknesses further undermine interpretability. 

Author Response

Although the topic is relevant, the manuscript substantially overlaps with prior reviews and does not provide sufficient original insight; methodological weaknesses further undermine interpretability.  

While we appreciate the reviewer’s feedback, we respectfully disagree. This study is original research, not a review, thus it should not be compared to prior reviews. We believe this study builds upon prior research looking at the role of HPV vaccination in HIV-positive patients as a means of prevention of HPV-related diseases, particularly given our findings that highlight the role of the provider in vaccination uptake.  

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript presents a cross-sectional survey assessing barriers to HPV vaccination among HIV-positive patients attending a county safety-net clinic in Houston, Texas. The topic is timely and highly relevant, particularly given persistent gaps in HPV vaccination coverage among high-risk populations such as people living with HIV. The study benefits from real-world clinical data, integration of survey and electronic medical record information, and a clear public health focus. The finding that provider recommendation and patient education substantially influence vaccine uptake is consistent with existing literature and reinforces the importance of provider-driven interventions.

Overall, the manuscript is clearly written and well-organised. However, several methodological clarifications, statistical inconsistencies, and language refinements are needed to strengthen the rigour and interpretability of the findings.

Title

• The title is clear and concise; however, consider specifying the study design (e.g., “A Cross-Sectional Survey”) to improve transparency and alignment with reporting standards.

Abstract

• Lines 10–13: The background is appropriate, but the objective could be more precise. Consider explicitly stating that the study evaluates patient- and provider-related barriers to HPV vaccination.
• Lines 14–20: The methods are clearly summarised. Consider specifying that vaccination status refers to receipt of at least one dose.
• Lines 21–22: The statement “lack of knowledge” would benefit from clarification (e.g., lack of patient knowledge vs lack of provider recommendation).
• Lines 24–25: Given the cross-sectional design, the absence of association between vaccination status and dysplasia history should be interpreted cautiously; consider adding a qualifying phrase.

Introduction

• Lines 32–36: The epidemiological background is accurate. Consider adding a brief statement acknowledging the role of non-16/18 oncogenic HPV types, particularly in immunocompromised populations.
• Lines 38–40: Well written; consider citing more recent HIV-specific HPV screening or vaccination guidelines if available.
• Lines 45–49: The description of vaccine eligibility could be clearer by explicitly distinguishing historical vs current FDA recommendations.
• Lines 55–57: Vaccine hesitancy discussion is relevant; consider briefly noting that provider hesitancy or omission may also contribute, particularly in adult populations.
• Lines 61–64: The local clinic context is a strength; however, clarify whether the reported 7% vaccination rate refers to full or partial vaccination.

Materials and Methods

• Lines 68–70: Inclusion criteria are clearly stated. Consider explaining the rationale for including participants over the age of the current vaccine eligibility.
• Lines 71–73: This is an important clarification; consider moving or reiterating this point earlier in the Methods to frame the interpretation of vaccination rates.
• Lines 74–77: Use of a convenience sample should be explicitly acknowledged as a potential source of selection bias.
• Lines 79–85: Survey domains are comprehensive. Consider stating whether the questionnaire was adapted from a validated instrument or developed de novo.
• Lines 85–86: Clarify whether surveyors were trained uniformly to minimise interviewer bias.
• Lines 89–91: The offer of vaccination post-survey is important and may influence outcomes; consider explicitly noting this as part of the study intervention rather than purely observational.
• Lines 96–99: The statement “Continuous variables were summarised as frequencies and percentages” appears to be an error and should be corrected to means/medians with appropriate dispersion measures.
• Lines 100–102:

• The use of one-way ANOVA for age comparisons across three groups (vaccinated, unvaccinated, unsure) is acceptable; however, justification for grouping “unsure” participants should be provided, or sensitivity analyses excluding this group should be considered.
• No multivariable analysis was performed. While this may be acceptable for an exploratory study, the authors should acknowledge that potential confounding factors (e.g., age, education, duration of HIV infection) were not adjusted for.

Results

• Lines 108–110: There is a discrepancy regarding the number of HIV-positive patients mentioned. The text states "a total of 132 HIV-positive patients," but Tables 1 and 2 indicate that there are only 131. Please correct this inconsistency. The demographic description is clear. However, the reported median age range (20–65) should be reconciled with the eligibility criteria.
• Line 111: Viral load categories could be better defined (e.g., specify thresholds for “detectable”).
• Lines 116–117: In Table 1, the "Missing or unknown" value for "Highest Level of Education" is 0; please remove this entry.
• Line 118: The strong association between awareness and vaccination status is important; consider reporting an effect size in addition to the p-value.
• Lines 123–126: Reasons for non-vaccination are clearly presented. Consider separating patient-level and provider-level barriers explicitly.
• Line 129: The high uptake after survey participation suggests an intervention effect; this should be highlighted more clearly.
• Lines 131–133: Age association is expected; consider stating that age may act as a proxy for eligibility.
• Lines 134–135: The lack of association with dysplasia history should be interpreted cautiously due to limited power and cross-sectional design.
• Table 2: Clarify what the “Mean (SD)” represents for co-testing; this variable is not intuitively continuous.
• Table 1 and Table 2 are informative but dense. Consider simplifying or moving less critical variables to supplementary material.
• Some table labels (e.g., “Pap and HPV co-testing available in medical record”) would benefit from clearer definitions.

Discussion

• Lines 138–142: The discussion appropriately emphasises education and provider recommendation. Consider more explicitly distinguishing knowledge gaps from access issues.
• Lines 144–147: This is a strong and clinically relevant observation; consider emphasising it as a key takeaway.
• Lines 154–163: The literature comparison is appropriate, but somewhat repetitive. Consider condensing similar findings into a single paragraph.
• Lines 165–172: The comparison with the Ontario study is insightful; however, differences in vaccine funding and healthcare structure should be emphasised earlier to avoid overgeneralization.
• Lines 173–179: The discussion of provider discomfort is relevant; consider linking this more directly to proposed interventions.
• Lines 189–194: Limitations are appropriately acknowledged. Consider explicitly stating that vaccination status was based on receipt of at least one dose.
• Lines 202–208: Future directions are appropriate; consider clearly separating future research from public health implementation strategies.
• Lines 209–222: Inclusion of males is an important point; consider briefly acknowledging that this study’s findings may not be generalizable to male populations.

Conclusions

• Lines 231–235: Conclusions are supported by the data. Consider softening causal language (e.g., “reveals” → “suggests”) given the study design.

Comments on the Quality of English Language

Minor Editorial Issues

• Several minor grammatical and typographical errors are present (e.g., duplicated punctuation, spacing issues, occasional tense inconsistencies). A professional language edit is recommended before publication.
• Ensure consistent use of terms such as Pap smear/Pap test and HPV vaccination/HPV vaccine throughout the manuscript.

Author Response

Reviewer 2 

This manuscript presents a cross-sectional survey assessing barriers to HPV vaccination among HIV-positive patients attending a county safety-net clinic in Houston, Texas. The topic is timely and highly relevant, particularly given persistent gaps in HPV vaccination coverage among high-risk populations such as people living with HIV. The study benefits from real-world clinical data, integration of survey and electronic medical record information, and a clear public health focus. The finding that provider recommendation and patient education substantially influence vaccine uptake is consistent with existing literature and reinforces the importance of provider-driven interventions. 

Overall, the manuscript is clearly written and well-organised. However, several methodological clarifications, statistical inconsistencies, and language refinements are needed to strengthen the rigour and interpretability of the findings. 

We greatly appreciate your time reviewing our manuscript. We have enhanced and clarified several points within the Materials and Methods, Results, and Discussion to strengthen the interpretability of our findings.  

Title 

• The title is clear and concise; however, consider specifying the study design (e.g., “A Cross-Sectional Survey”) to improve transparency and alignment with reporting standards. 

Thank you for this suggestion, we have incorporated this change into the manuscript. 

Abstract 

• Lines 10–13: The background is appropriate, but the objective could be more precise. Consider explicitly stating that the study evaluates patient- and provider-related barriers to HPV vaccination. 

Thank you for this suggestion. To clarify, we sought to evaluate specifically patient barriers to HPV vaccination through self-reported surveys and by asking about limitations they may have faced. We did not seek to evaluate provider-related barriers at the start of our study, but encountered them through discussions with participants. 

• Lines 14–20: The methods are clearly summarised. Consider specifying that vaccination status refers to receipt of at least one dose. 

Thank you for this suggestion, we have incorporated this change into the manuscript in lines 18-19. 

• Lines 21–22: The statement “lack of knowledge” would benefit from clarification (e.g., lack of patient knowledge vs lack of provider recommendation). 

Thank you for addressing this. We have clarified our findings in the abstract in lines 25-26 along with in the results/discussion. The most common reason for not receiving the vaccine was never being offered the vaccine before. 

• Lines 24–25: Given the cross-sectional design, the absence of association between vaccination status and dysplasia history should be interpreted cautiously; consider adding a qualifying phrase. 

Thank you for this suggestion, we have incorporated this change into the manuscript in lines 29-30. 

Introduction 

• Lines 32–36: The epidemiological background is accurate. Consider adding a brief statement acknowledging the role of non-16/18 oncogenic HPV types, particularly in immunocompromised populations. 

Thank you for this suggestion. We have incorporated this change into the manuscript in lines 45-48. 

• Lines 38–40: Well written; consider citing more recent HIV-specific HPV screening or vaccination guidelines if available. 

Thank you for this suggestion. We have incorporated more recent HIV-specific vaccination guidelines in the introduction, see lines 64-74. 

• Lines 45–49: The description of vaccine eligibility could be clearer by explicitly distinguishing historical vs current FDA recommendations. 

Thank you for your suggestion. This was noted by other reviewers as well. We have provided clarification to more clearly distinguish between historical and current FDA recommendations, also within line 60-74. 

• Lines 55–57: Vaccine hesitancy discussion is relevant; consider briefly noting that provider hesitancy or omission may also contribute, particularly in adult populations. 

Thank you for your suggestion. We have incorporated the role of provider hesitancy in lower vaccine uptake in lines 85-86. 

• Lines 61–64: The local clinic context is a strength; however, clarify whether the reported 7% vaccination rate refers to full or partial vaccination. 

Thank you for this note, we have now clarified this point in lines 92-93. 

Materials and Methods 

• Lines 68–70: Inclusion criteria are clearly stated. Consider explaining the rationale for including participants over the age of the current vaccine eligibility. 

Thank you for this suggestion, as noted by other reviewers. We have incorporated this change into the manuscript in line 104-107. 

 

• Lines 71–73: This is an important clarification; consider moving or reiterating this point earlier in the Methods to frame the interpretation of vaccination rates. 

Thank you for this suggestion. We have added more content to this clarifying point to enhance organization of the eligibility criteria in lines 75-78.  

 

• Lines 74–77: Use of a convenience sample should be explicitly acknowledged as a potential source of selection bias. 

We have added the suggested content to the manuscript within both the “Materials and Methods” and Limitations section within the Discussion on lines 120-128, and lines 314-317, respectively:  

 

“Patients were approached before or after their appointments in private clinic rooms. Attempts were made to approach each eligible patient, although some patients completed appointments before surveyors were able to approach them. Participation was voluntary and did not affect their clinical visit. Surveyors were uniformly trained to minimize interview bias.” 

 

“Limitations of this study include selection bias, recall bias and the age distribution of participants, with a proportion over age 45 and therefore ineligible for vaccination. Participants were recruited during their clinical visit and participation was voluntary. Because of this, the sample may overrepresent patients more willing to engage in research or with more positive preexisting attitudes towards HPV vaccination.” 

 

• Lines 79–85: Survey domains are comprehensive. Consider stating whether the questionnaire was adapted from a validated instrument or developed de novo. 

Thank you for this suggestion. The survey was developed de-novo. We have added this to the “Materials and Methods” section on line 113-114.  

• Lines 85–86: Clarify whether surveyors were trained uniformly to minimise interviewer bias. 

Thank you for bringing this up. We have clarified this on lines 127-128.  

• Lines 89–91: The offer of vaccination post-survey is important and may influence outcomes; consider explicitly noting this as part of the study intervention rather than purely observational. 

Thank you for pointing this out, as noted by other reviewers. We have added additional context to this finding in the “Materials and Methods” section on lines 136-140.  

 

“Following survey administration and counseling about the vaccine, including safety, side effects, and prevention of cervical cancer and other HPV-related diseases, patients were asked if they wanted to receive the vaccine. If patients wanted to receive the vaccine, surveyors collaborated with their physician and nursing staff during their visit based on their eligibility criteria. Counseling provided by the surveyors did not replace that discussed by the providing team, as it standard in a clinical context.”    

 

• Lines 96–99: The statement “Continuous variables were summarised as frequencies and percentages” appears to be an error and should be corrected to means/medians with appropriate dispersion measures. 

Thank you for pointing this out, as noted by other reviewers. We have updated this in lines 106-109.  

 

• Lines 100–102: The use of one-way ANOVA for age comparisons across three groups (vaccinated, unvaccinated, unsure) is acceptable; however, justification for grouping “unsure” participants should be provided, or sensitivity analyses excluding this group should be considered.  

 

We agree with the reviewer’s assessment. We have performed a sensitivity analysis for Table 1 excluding the participants who were unsure about prior vaccination status and found that this exclusion did not meaningfully affect the results. We have added relevant discussion of this to the Materials and Methods and Results found in lines 154-158 and 174-176, respectively.  

 

“A sensitivity analysis was performed to exclude participants who were unsure about prior vaccination status using the same statistical methods to assess for robustness of findings.“ 

 

“Results were similar in sensitivity analyses excluding participants who were unsure about prior vaccination status (“Unsure”).” 

 

• No multivariable analysis was performed. While this may be acceptable for an exploratory study, the authors should acknowledge that potential confounding factors (e.g., age, education, duration of HIV infection) were not adjusted for. 

Thank you for this suggestion. We have commented on this point in lines 156-158.  

Results 

• Lines 108–110: There is a discrepancy regarding the number of HIV-positive patients mentioned. The text states "a total of 132 HIV-positive patients," but Tables 1 and 2 indicate that there are only 131. Please correct this inconsistency. The demographic description is clear. However, the reported median age range (20–65) should be reconciled with the eligibility criteria. 

Thank you for addressing this error. We have amended the manuscript to reflect n=131.  

 

• Line 111: Viral load categories could be better defined (e.g., specify thresholds for “detectable”). 

Thank you for pointing this out. We have updated the language to stratify participants by having a viral detectable load (> 200 copies/mm3) or viral suppressed (<200 copies/mm3).   

 

• Lines 116–117: In Table 1, the "Missing or unknown" value for "Highest Level of Education" is 0; please remove this entry. 

Thank you for addressing this error. We have updated Table 1 accordingly.  

 

• Line 118: The strong association between awareness and vaccination status is important; consider reporting an effect size in addition to the p-value. 

 

We appreciate the reviewer’s suggestion and agree that reporting an effect size will strengthen the interpretation of this result. We have calculated and included an odds ratio for the relationship between the HPV vaccine awareness and vaccination status variables on lines 178-183.  

 

“Awareness of the vaccine was strongly associated with vaccination status. Partipcants who had heard of the HPV vaccine had significantly higher odds of being vaccinated compared to those who indicated they had not heard of the HPV vaccine (OR 11.05, 95% CI: 2.50-48.84, p<0.001).” 

 

• Lines 123–126: Reasons for non-vaccination are clearly presented. Consider separating patient-level and provider-level barriers explicitly. 

There may be an error in the wording of this comment affecting the interpretation. This survey did not account for provider-level barriers in prior vaccination status, rather solely asked patients about limitations in prior receipt of the HPV vaccine.  

 

• Line 129: The high uptake after survey participation suggests an intervention effect; this should be highlighted more clearly. 

We agree that survey participation likely affected vaccine uptake. This study was observational by design but given the clinical nature of the environment in which this study was performed as well as availability of the vaccine at the clinic at no cost to the patient, information was provided after the survey about the vaccine. If patients responded that they wanted the vaccine, we coordinated with their physician to provide them the vaccine given they met eligibility criteria. We have clarified this information in the manuscript on lines 136-140. 

 

“Following survey administration and counseling about the vaccine, including safety, side effects, and prevention of cervical cancer and other HPV-related diseases, patients were asked if they wanted to receive the vaccine. If patients wanted to receive the vaccine, surveyors collaborated with their physician and nursing staff during their visit based on their eligibility criteria. Counseling provided by the surveyors did not replace that discussed by the medical care team, as it is standard in a clinical context.”    

 

• Lines 131–133: Age association is expected; consider stating that age may act as a proxy for eligibility. 

We agree with the reviewer’s assessment and have added this context to line 199.  

 

• Lines 134–135: The lack of association with dysplasia history should be interpreted cautiously due to limited power and cross-sectional design. 

You are certainly correct. We have updated the discussion with our reflection on this topic.  

• Table 2: Clarify what the “Mean (SD)” represents for co-testing; this variable is not intuitively continuous. 

Thank you for pointing out this error. The variable was entered as integers in the original data set and was not factored to more interpretable levels when transferring to the manuscript. Given this variable does not inform the key results of this study, we have eliminated it from Table 2.  

 

• Table 1 and Table 2 are informative but dense. Consider simplifying or moving less critical variables to supplementary material. 

Thank you for this suggestion. We have eliminated “Ethnicity” and “Sexual Orientation” in Table 1 as these variables do not inform the key results or discussion. Similarly, we have eliminated “Pap and HPV co-testing available in the medical record” in Table 2.  

  

• Some table labels (e.g., “Pap and HPV co-testing available in medical record”) would benefit from clearer definitions. 

Thank you for addressing this error. The variable was entered as integers in the original data set and was not factored to more interpretable levels when transferring to the manuscript. Given this variable does not inform the key results of this study, we have eliminated it from Table 2.  

Discussion 

• Lines 138–142: The discussion appropriately emphasises education and provider recommendation. Consider more explicitly distinguishing knowledge gaps from access issues. 

Thank you for this suggestion. We have clarified our findings to emphasize lack of provider offering vaccination as the most common reason in lines 222-223.  

• Lines 144–147: This is a strong and clinically relevant observation; consider emphasising it as a key takeaway. 

Thank you for this suggestion. We have emphasized this observation in the discussion in lines 234-237 as well as added it to our abstract.  

• Lines 154–163: The literature comparison is appropriate, but somewhat repetitive. Consider condensing similar findings into a single paragraph. 

Thank you for your recommendation. We have condensed the literature comparison in lines 240-252 to be less repetitive and more impactful. 

• Lines 165–172: The comparison with the Ontario study is insightful; however, differences in vaccine funding and healthcare structure should be emphasised earlier to avoid overgeneralization. 

Thank you for this suggestion. We have amended the order of the paragraphs to include earlier discussion of the differences between the two healthcare systems in lines 264-282 and contrasting factors. 

• Lines 173–179: The discussion of provider discomfort is relevant; consider linking this more directly to proposed interventions. 

Thank you for this suggestion. We have expanded our discussion of provider discomfort and linked to several studies, as well as detailing potential interventions in lines 247-257. 

• Lines 189–194: Limitations are appropriately acknowledged. Consider explicitly stating that vaccination status was based on receipt of at least one dose. 

Thank you for your suggestion. We now explicitly stated that vaccination status was based on receipt of at least one dose, which does not distinguish between partial and series completion, in the limitations. See lines 322-324. 

 

• Lines 202–208: Future directions are appropriate; consider clearly separating future research from public health implementation strategies. 

Thank you for your suggestion. We have specified the future directions from future public health implementation strategies. See lines 335 and 343. 

 

• Lines 209–222: Inclusion of males is an important point; consider briefly acknowledging that this study’s findings may not be generalizable to male populations. 

Thank you for your suggestion. We have incorporated this into the limitations section of the discussion section. See lines 318-319. 

 

 

Conclusions 

• Lines 231–235: Conclusions are supported by the data. Consider softening causal language (e.g., “reveals” → “suggests”) given the study design. 

Thank you for this suggestion. We have incorporated this change into the manuscript. See line 370. 

Minor Editorial Issues 

• Several minor grammatical and typographical errors are present (e.g., duplicated punctuation, spacing issues, occasional tense inconsistencies). A professional language edit is recommended before publication. 

We have tightened our language and grammar. All authors are native English speakers (American English) and we do not think a professional language edit would be beneficial. 

• Ensure consistent use of terms such as Pap smear/Pap test and HPV vaccination/HPV vaccine throughout the manuscript. 

We have checked for this and updated where indicated. 

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

1. The conclusion in the abstract need to be revised instead of “likely increase” vaccination be more specific like “Integrating vaccination prompt into HIV primary health care.
2. Check whether the Global health stats on HPV in US is up to date. Comment on the risk of HIV positive women in developing cervical cancer compare to the HIV negative.
3. What is the biological interaction between HIV and HPV? The role of HIV tat?
4. In line 62, clarify the difference on 7% and 33%. In your introduction you have mention 7% had receive vaccine but in the abstract is 33%.
5. Please clarify the confusion in line 56; you mention the stigma in adolescence but your study is adults. What is the reaction of adults toward vaccine? Please state that clear.
6. Explain the vaccine schedule clearly. For HIV-1 positive patients, the CIP recommends 3 dose schedules regardless of age.
7. I suggest that authors include the study design diagram on how the participants were included in the study. Schematic diagram
8. In 79-72, you explain that patients over 52 were likely ineligible because they over 45 in 2018, however you included patients up to 65 years. Please clarify.
9. In line 73, explain briefly the recruitment period and whether surveyor approach every patient in the waiting room or selected them randomly.
10. In line 98, “Continuous variable are summarised as frequencies and percentages. Normally continuous variable (age) are summarized in mean (SD) or median (IQR).
11. Please clarify “vaccinated” mean they had at least one dose or completed 3 doses required for HIV patients
12. Does "Vaccinated" (N=44) mean they had at least one dose (as mentioned in line 117) or the complete 3-dose series required for HIV patients? It is helpful to specify this, as a single dose is less effective in immunocompromised individuals.
13. Line 123 states 51% were "never offered" the vaccine. In your discussion, you should contrast this with the fact that 58% of those who were aware heard it from a provider. This confirms that the provider is the "gatekeeper."
14. You mention 41% are undetectable. You might want to briefly check if there is a correlation between HIV viral suppression and vaccination status (i.e., do patients with "better" HIV care also get "better" HPV care?).
15. In Table 2, "Any abnormal Pap Smear (reported)" shows nearly 50% across the board. This high prevalence of cervical dysplasia underscores the high-risk nature of your sample and makes the 7% clinic-wide uptake rate even more alarming.
16. lines 186–189, you discuss the provider’s role. Explicitly mention that for the 27–45 age group, the CDC recommends SCDM. Your data shows this "sharing" isn't happening, which is a specific clinical failure.
17. In line 226, mentioning patients with only a second-grade education is a powerful detail. Suggest that visual aids or low-literacy infographics are needed for this specific safety-net population.

Author Response

Reviewer 3 

1. The conclusion in the abstract need to be revised instead of “likely increase” vaccination be more specific like “Integrating vaccination prompt into HIV primary health care. 

Thank you for this suggestion. We have revised the statement to be more specific. See lines 34-35. 

 

2. Check whether the Global health stats on HPV in US is up to date. Comment on the risk of HIV positive women in developing cervical cancer compare to the HIV negative. 

3. What is the biological interaction between HIV and HPV? The role of HIV tat? 

Thank you for this suggestion. We have reviewed the epidemiologic data on HPV in the US and confirmed that the statistics presented are current. We have revised the introduction to explicitly include the increased risk of cervical cancer among women living with HIV. In addition, we have clarified the biological interaction between HIV and HPV, emphasizing the role of HIV-associated immunosuppression in impairing HPV clearance. We have further expanded this section to discuss the role of HIV Tat in promoting HPV-mediated carcinogenesis. See lines 50-57. 

 

4. In line 62, clarify the difference on 7% and 33%. In your introduction you have mention 7% had receive vaccine but in the abstract is 33%. 

We appreciate your comment. In the introduction, we mentioned 7% had received the vaccine in 2023 per a quality review of clinical data. In the abstract, we report our findings from this study showing 33% of patients reported HPV-vaccination in our current. The 7% data is 2 years old, but also is a comprehensive data pull from the whole clinic population, whereas our survey was a convenience sample. 

5. Please clarify the confusion in line 56; you mention the stigma in adolescence but your study is adults. What is the reaction of adults toward vaccine? Please state that clear. 

Thank you for this suggestion. This was also noted by other reviewers. We have amended this to include more information on vaccine hesitancy in adult populations. See lines 79-87. 

6. Explain the vaccine schedule clearly. For HIV-1 positive patients, the CIP recommends 3 dose schedules regardless of age. 

Thank you for this suggestion. We have updated the vaccine schedule for greater clarity. See lines 58-73. 

 

7. I suggest that authors include the study design diagram on how the participants were included in the study. Schematic diagram 

Thank you for your recommendation. We have added additional context to the recruitment process in the Materials and Methods section in lines 113-140.  We do not have a schematic diagram given that this was a convenience sample for a cross-sectional survey. 

 

8. In 79-72, you explain that patients over 52 were likely ineligible because they over 45 in 2018, however you included patients up to 65 years. Please clarify. 

We began the survey with all female patients at the Thomas Street Clinic because we were interested in the attitudes of the population as a whole, as well as the potential that the vaccine age could be expanded in the future, or that these patients have influence on others in their families.  

To provide further clarification to the attitudes of eligible patients, we have stratified Table 1 by age group to include those eligible and ineligible for the vaccine.  

 

9. In line 73, explain briefly the recruitment period and whether surveyor approach every patient in the waiting room or selected them randomly. 

Thank you for this suggestion. We have expanded on this point in lines 122-127.  

 

10. In line 98, “Continuous variable are summarised as frequencies and percentages. Normally continuous variable (age) are summarized in mean (SD) or median (IQR). 

Thank you for addressing this error, as noted by other reviewers. We have amended this on lines 106-108.  

 

11. Please clarify “vaccinated” mean they had at least one dose or completed 3 doses required for HIV patients 

This question was posed to participants as, “Have you ever received the HPV vaccine?;” therefore “vaccinated” is a self-reported variable regardless of the number of doses. We have updated the “Materials and Methods” section to better explain this variable in lines 119-121.  

 

12. Does "Vaccinated" (N=44) mean they had at least one dose (as mentioned in line 117) or the complete 3-dose series required for HIV patients? It is helpful to specify this, as a single dose is less effective in immunocompromised individuals. 

We appreciate this suggestion and have provided clarification for this variable throughout the “Materials and Methods” and “Results” sections, including within the table headings, “Vaccinated prior to survey.”   

 

13. Line 123 states 51% were "never offered" the vaccine. In your discussion, you should contrast this with the fact that 58% of those who were aware heard it from a provider. This confirms that the provider is the "gatekeeper." 

Thank you for this suggestion. We have included this comparison in line 222. 

 

14. You mention 41% are undetectable. You might want to briefly check if there is a correlation between HIV viral suppression and vaccination status (i.e., do patients with "better" HIV care also get "better" HPV care?). 

Thank you for this helpful recommendation. We have added a Viral Suppression variable (<200 copies/mm3) to Table 1 to demonstrate there was no significant association between being viral suppressed and HPV vaccination status.  

 

15. In Table 2, "Any abnormal Pap Smear (reported)" shows nearly 50% across the board. This high prevalence of cervical dysplasia underscores the high-risk nature of your sample and makes the 7% clinic-wide uptake rate even more alarming. 

You are correct about this. This highlights the “high risk” nature of our population, as expected. We have added to the discussion a note on this finding in lines 296-303. 

 

16. lines 186–189, you discuss the provider’s role. Explicitly mention that for the 27–45 age group, the CDC recommends SCDM. Your data shows this "sharing" isn't happening, which is a specific clinical failure. 

Thank you for this suggestion. We have added a section highlighting this clinical failure in the discussion. See lines 309-315. 

17. In line 226, mentioning patients with only a second-grade education is a powerful detail. Suggest that visual aids or low-literacy infographics are needed for this specific safety-net population. 

Thank you for this suggestion. We included this at the end of our discussion. See lines 364-365. 

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

Please see attached word file. 

Comments for author File: Comments.pdf

Author Response

Reviewer 4 

General Comments:  

• The intent of this research to describe uptake of HPV vaccine in an HIV clinic was an important endeavor. However, the study design was a bit confusing, and it is unclear why adults up to age 65 were included. Furthermore, the data were not presented such that the reader could easily understand the data for those <45 years (X of 132 ) vs those 45 and older (0r those age eligible vs those who were not eligible). There is little need to vaccinate those 45 and older, but there is great need to determine how to vaccinate those <45 years and that should be the focus of the data analysis. (If there is an obvious reason to have surveyed those 46-65 years of age this should be clearly stated in the text.) The data definitely need to be presented by age group, not just who was previously vaccinated and who was not. This would likely require a fairly major revision of the data analysis and manuscript. You will see several instances in the specific comments below where presentation of data by age would be so much more useful. 

Thank you for this comment. We set out to survey our female HIV-positive clinic population regarding their attitudes toward HPV vaccination. We decided to include our entire clinic population despite the older patients possibly having not been eligible to receive the vaccine. Patients 46-65 were included in the study to comprehensively evaluate knowledge, prior vaccine exposure, and attitudes towards vaccination in a population that may have been counseled under evolving guidelines. 

We have extensively updated our manuscript to better clarify this issue, including using your excellent and detailed feedback below. We will respond individually to your comments below in how we have updated the manuscript. 

Specific Comments:  

• Title – suggest adding vaccination of “females” to the title since no males were included. 

Thank you for your suggestion. We considered adding “female”, but we feel the current title accurately reflects the study scope and population, and we prefer to keep it concise while maintaining clarity. 

• Abstract – add year survey conducted. Add something about % who agreed to be vaccinated after the survey. This is an important finding worth highlighting. 

Thank you for your suggestion. We have now incorporated it into the abstract. See lines 31-32. 

• Line 15 - add the age of the study participants. 

Thank you for your suggestion. We have incorporated the age into the abstract. See lines 15-16. 

• Line 26 – what data support that education of providers should be increased? While this may be true, the reader does not receive any information on the education level of the patient’s providers to substantiate this recommendation. 

Thank you for your suggestion. We have clarified the statement in the abstract to  support clinicians in delivering confident counseling in lines 35-36. We have also included a reference in the discussion in lines 255-263 supporting lack of provider confidence in having these discussions.  

• Line 23 -24 – seeing the mean ages of 38.4 v s 51.0 years instantly leaves the reader with a lack of understanding of why older females were included in the survey. Limiting to vaccine eligible participants would be much more useful and easier to follow. 

Thank you for your suggestion. We have removed this line from the abstract for clarity. 

 

• Line 45 – best to clarify vaccine was approved by the FDA and that its use was recommended by the ACIP as shared clinical decision making etc. (FDA does not make recommendations.) 

Thank you for your suggestion. We have added a clarification to this portion of the introduction to make the recommendation by the ACIP clearer. See lines 63-65. 

• Lines 59-64 – describe the study population here. On line 167 you first describe the SES of the study population. This should come earlier. 

Thank you for your suggestion. We added more SES information in lines 88-90. 

• Line 67 – add the month and year the survey was conducted. 

Thank you for pointing this out. We have incorporated this change into the manuscript in line 98.  

• Line 70 – consider limiting the entire analysis in this paper to those 18-45 years or explain in more detail why those 46-65 were included. The paper is very confusing & hard to follow because those age 65 were too old to be vaccinated in 2006 (and certainly in 2018) when the vaccine was first licensed/recommended. 

Thank you for this suggestion. We have included additional content and justification for our eligibility criteria, including patients ages 46-65 in lines 122-128.  

 

• Line 92 – Clinical data” were obtained (not “was”). 

Thank you for pointing this out. We have incorporated this change into the manuscript.  

 

• Line 108 – Is the N 132 as shown here or 131 as shown in Table 1. Please correct so they match. 

Thank you for pointing this out. We have changed all instances to reflect N=131.  

 

• Table 1: Show the data by age group (<45, 46-65 yrs.) or just present data for only those participants <45 (or age eligible for vaccination) through the entire manuscript. Column headers should say Vaccinated “Prior to Survey” and Unvaccinated “Prior to Survey”. 

Thank you for this suggestion. We have incorporated these changes into the manuscript in Table 1.  

• Add a row showing the % who received the vaccine after the survey. This is important data. 

Thank you for this suggestion. We have incorporated this change into the manuscript in Table 1.   

• The value of the highly significant finding about who had heard of the HPV vaccine is questionable because it is confounded by the age of the participant. The reader is not interested in the responses of 65-year-olds who are not eligible for vaccination. 

For this pilot study, we began the survey with all female patients at the Thomas Street Clinic because we were interested in the attitudes of the population as a whole, as well as the potential that the vaccine age could be expanded in the future, or that these patients have influence on others in their families.  

To provide further clarification to the attitudes of eligible patients, we have stratified Table 1 by age group to include those eligible and ineligible for the vaccine.  

 

• Line 117 – limit analysis to those who could have been age eligible for the vaccine. Present the data by age groups. 

Thank you for your suggestion. We agree that it would be helpful to focus on age-eligible participants, but the nature of this survey was to explore attitudes towards vaccination of Thomas Street patients as a whole. To further clarify differences between age-eligible and ineligible participants, we have stratified by age in Table 1.  

 

• Line 129 - how many eligible unvaccinated participants were there? Assume this is 45-year-olds and younger only. Please add. 

Thank you for this suggestion. We have incorporated this change into Table 1. 

• Lines 143-152 – once again, the presentation of the results is not clear because of the age range of the entire study population. Strongly recommend limiting to those 45 and younger as they are the ones for whom vaccination is still needed. ( It is too late for those 46-65 years).Did you look at what % of those who were vaccinated received all 3 doses and if they different from those who received only 1 dose? This would be useful data as well. 

Thank you for this important comment. We agree that HPV vaccination eligibility is influenced by age. Our study, however, was designed to evaluate knowledge, attitudes, and vaccination patterns across the full clinic population rather than to assess vaccine eligibility or clinical need exclusively among those ≤45 years. While we have kept participants > 65 years in the analysis, we have stratified by subgroup in Table 1 as well as added additional context and discussion of limitation in the Materials and Methods and Discussion, respectively.  

Regarding vaccine series completion, we agree this is valuable. Unfortunately, dose-level completion data were not consistently available during chart abstraction, which precluded reliable analysis of three-dose completion versus partial vaccination.  

 

• Lines 176-177 – suggest this sentence be removed or reworded. Mandates are not routine for HPV vaccine. The ACIP does not mandate vaccines, but HPV vaccine has been recommended by them for almost 20 years, and all HCPs know that vaccines on the ACIP schedule should be discussed with patients. The vaccine is routinely recommended for adolescents and simply should be discussed. (Mandates are not well received these days.) 

Thank you for your suggestion. We have removed the mandate portion of the discussion and instead are focusing on shared clinical decision making.  

• Line 181 – what data do you have to support that the HCPs for these study participants did not discuss HPV vaccine? This statement should be made with caution as you did not check medical records to see if the vaccine was discussed or contact any of the participants’ HCPs. 

Thank you for your comment. Our study focused on patient-reported data.  

Our participants reported not having discussions with their providers about the HPV vaccine (i.e. had never been offered the vaccine by a physician or medical provider), which is what our claim is based on. 

• Lines 181-188 – the reasons for not being vaccinated discussed here would be important to have in a table – as long as it is stratified by age. 

Thank you for your helpful suggestion. We have included additional Figures 1-2 to provide better context for reasons why participants were not vaccinated prior to the survey.  

• Line 190 – need to note in limitations that use of surveyors to interview participants could impact honesty of responses (vs using a written, anonymous survey). 

Thank you for your suggestion. We have included interview-bias into the limitations.  

• Line 190-194 - what proportion of participants were >45 years? This section is a bit confusing & could be easily corrected by limiting the data presentation from the entire survey to those who were age eligible for vaccination. That would make these results much more useful and less confusing. 

Thank you for your suggestion. We have included the percentage of participants over the age of 45. However, we wanted to leave in the remainder of the data to prevent cherry-picking.  

• Lines 209-222 – while agree that vaccination of males is important, this is not the focus of this research and would just limit to 1-2 sentences. 

Thank you for your comment. To address the concern about length, we have condensed the discussion of HPV vaccination in males while keeping it long enough to highlight its relevance and importance for future research directions. See lines 343-358. 

• Conclusions – would note that HCPs should seize every opportunity to vaccinate including after a survey like this. You had a good vaccine uptake after the survey & that should be emphasized in the Discussion and the Conclusions. 

Thank you for your suggestion. We have highlighted the good vaccine uptake in the conclusion. See lines 369-371. 

 

Author Response File: Author Response.pdf

Reviewer 5 Report

Comments and Suggestions for Authors

please see uploaded report

Comments for author File: Comments.pdf

Author Response

Reviewer 5 

The authors conducted a cross-sectional survey among HIV-positive individuals attending 

a single urban safety-net clinic to assess knowledge and attitudes on HPV vaccination. 

The manuscript addresses a relevant and interesting topic. However, clarification of several 

methodological aspects and of Results is necessary. 

Abstract 

- It is incorrect to use the term “more virulent forms of HPV” in scientific language. It 

would be more appropriate to refer to “high-risk HPV genotypes” as defined by the 

IARC. 

Thank you for this suggestion. The change has been incorporated into the manuscript in line 14.  

Introduction 

• Lines 34-35: Please update this information. More than 200 HPV genotypes have 

been identified (e.g. doi: 10.3390/v7072802, or a more recent article). 

Thank you for this suggestion. We have updated the language to include 200 genotypes and included an additional reference in lines 43-45. 

Materials and Methods 

• It should be more appropriate to divide “Materials and Methods” section in 

subparagraphs (e.g., “study population and exclusion/inclusion criteria”, 

“questionnaire administration and clinical data acquisition”, “statistical analysis”). 

Thank you for this suggestion. We have added subheadings to the “Materials and Methods” section to enhance readability and organization.  

• Line 71: The manuscript does not specify when the survey was conducted and 

questionnaire administered. 

Thank you for pointing this out. This was also noted by other reviewers, and we have incorporated this change into the manuscript in line 96.  

• Lines 69-73: The authors include participants aged 18–65 but then specify that the 

individuals over the age of 52 would not have been eligible. Although this point is explained in the discussion as a limitation (lines 190-195), please justify the inclusion of these participants in the “Materials and Methods” section. 

Thank you for this suggestion. This was noted by other reviewers, and we have included justification for inclusion of the subset of the population in lines 102-105.  

 

• Line 74: The use of a convenience sample could generate a selection bias. Please discuss this potential phenomenon and its impact on the survey results. In addition, how many individuals refused to participate to the survey? 

Thank you for this suggestion, as noted by other reviewers. We have added additional content on lines 186-188 and in the Limitation section on lines 106-110. We did not track the number of participants approached versus agreed to participate in the survey.  

• Lines 99: “Continuous variables were summarized as frequencies and percentages”: Rather than using this expression, it would be more appropriate to specify that mean ± SD or median [IQR] was used for continuous variables. 

Thank you for this suggestion. We have incorporated this change into the manuscript.  

Results 

• Please report percentages accurately in the text so that they match those in the tables or add “about” if you want to round the number (line 110 “63%,” line 112 “40%,”line 114 “90%,” line 117 “75%”). Also, add “data not shown” to the percentages reported in the text but not described in a table (lines 110-112). 

Thank you for pointing this out. We have incorporated these changes to the Results section.   

• Lines 123-127: It is surprising that, despite the fundamental issue addressed in the paper being awareness of HPV vaccination and the possible reasons for lack of awareness, there is no table highlighting the results relating to this topic. 

Thank you for this suggestion. We have added “Figure 1. Sources of Information for Prior Knowledge of HPV Vaccine” to line 205 and “Figure 2. Reasons Patients Did not Receive the HPV Vaccine Prior to Survey” to line 208 in the Results section to further elaborate on this important finding.  

Discussion  

It is unclear why the authors want to explore associations between HPV vaccination status and cytological abnormalities if they do not include any comments on this in the discussion. 

Thank you for this suggestion. We have included a discussion exploring HPV vaccination and dysplasia history in lines 291-300. 

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

The authors have done a excellent job of responding to my comments on clinical and biological critiques into specific manuscript improvements.  The addition of the HIV Tat protein discussion and stratification of data by age and viral suppression significantly elevates the sceintific rigor of the paper. Including the role of HIV Tat in HPV-mediated carcinogenesis is a high-level addition that shifts the paper from a simple survey to a more robust clinical-biological study.The authors’ willingness to explicitly label the lack of Shared Clinical Decision-Making (SCDM) for the 27–45 age group as a "clinical failure" adds a powerful, advocacy-driven edge to the Discussion.The explanation for the discrepancy between the 7% (clinic-wide) and 33% (surveyed) vaccination rates is honest and scientifically sound. Stratifying Table 1 by age to address the inclusion of older patients (up to 65) clarifies the "denominator" issue.Responding to the "second-grade education" detail by suggesting low-literacy visual aids makes the study’s conclusions highly actionable for safety-net clinics.

Reviewer 5 Report

Comments and Suggestions for Authors

The authors discussed and included every suggestion . I accept the manuscript in present form.