Designing Inclusive HPV Cancer Vaccines and Increasing Uptake among Native Americans—A Cultural Perspective Review

Round 1

Reviewer 1 Report

Dear Authors,

Both Americas are a melting-pot of nations of the whole world and frequently there is no place for Natives, genuine Americans. Medical science should take into account not only the most common ones, but the whole society. It’s necessity, not vanity. The difference is the most visible between overrepresented in studies non-Hispanic Euro-Americans and the rest. We should know how to prevent diseases of the rest, to diagnose and cure them - there may be and there are differences between ethnic groups. We have to take care of the whole society, in many ways, even ecological and economical. Deforestation and poverty of Africa may be an explanation of both HIV and Ebola virus epidemics. Africans or Native Americans’ problems may be problems of the others. But studies are not enough, we have to work among our patients, both medical professionals and medical scientists. I really appreciate your focus on Native Americans.

Below there are some suggestions for You:

Title

• There is not much about personalized vaccines in the manuscript.  And nothing about future HPV prevalence studies among Native Americans. 

Affiliations

• Department of Health of Sciences? https://nau.edu/health-sciences/

Simple summary and Abstract

• What is the difference? What is the purpose of both of them? I see no reason. They are overlapping. Reject ‘simple summary’.

Introduction

• Not typical, but provides sufficient background
• 1.1, line 69-70; what do you mean saying ‘the development of Pap-smear’ - frequency of screenings? Or what?
• 1.1, line 71; ‘testng? What testing? PCR?
• 1.2, line 83-84; There are more hrHPV, e.g. 53, 66, 73, 82.
• 1.2.; When some HPV type is indicated by their number, do not use ‘hr-’ prefix, please. In case of presence of lrHPV, the prefix can be considered.
• 1.2, line 88 - which meta-analysis? the meta-analysis you referred to in the sentence before  [12]? 
• 1.2; line 104; indicate the exact source of the data of the figure 1, please
• figure 1; Hopi - other, whether HPV 16, 18 as well? 

2. Chapter

• I don't feel qualified to judge. Everything seems to be correct. The chapter provides important historical background, not entirely historical.

3. Chapter

• 3.2, line 288-290; ‘The most prevalent hrHPV types in cervical cancers among Native American women is unknown. Therefore, future HPV vaccines must provide broader coverage for types not found in the general population’. No, therefore hrHPV prevalence among Native American women should be studied. 
• 3.2; Examples of Hopi or another racial/ethnic group (or nation) should be taken into account. Otherwise, the whole 3.2. should be rejected, because thesis  ‘The General Population does not Always Represent the Whole’ is not confirmed there. 

4. Chapter

• In truth, I am not a specialist of public health and I shouldn't judge the whole concept.
• 4.1.1, line 351-352. Really? When tribes do like it, we will publish results - when not, we won’t? It’s against science, it’s against objectivism. Acting without and beyond permission as well as doing science with particular influence of examined ones are against basic laws of science. 
• 4.5; very well
• 4.6, line 415; the first human inhabitants; 
• 4.6, line 415; they were or they have been? I am not a native English speaker, maybe I am wrong. 

 

References

• [7] and [13] are the same. I do not recommend to change it, if you do it manually

 

Greetings from Europe and good luck

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

The paper is an important contribution to the field. The recommendations provided by the authors to increase Native American engagement is really important. My comments are listed below:

1. In section 4.2. Tribal Data Control and Ownership, if the authors find it appropriate, it may be helpful to frame data control under the context of Indigenous data sovereignty. If the authors feel it's appropriate, they could also define Indigenous data sovereignty as "the right of a nation to govern the collection, ownership, and application of its own data". 

2. Although the CONSIDER statement is a reporting guideline on health research involving indigenous people, it contains elements of governance, prioritization, relationships, etc., some of which are covered in this paper. I am not sure if there is a way to harmonize or standardize research with and of tribal populations with your recommendations in the paper and the CONSIDER statement. It may be helpful for the authors to comment on this in the paper; however, it is not required of them. 

3. In line 116, I think the authors meant to say Hopi.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Dear Authors,

I checked your changes. Below there are some suggestions to You: one minor, second major. 

 

Best regards and good luck

 

1.

Me: 1.2, line 88 - which meta-analysis? the meta-analysis you referred to in the sentence before [12]?

Your response: 1.2, line 102; Yes, the meta-analysis referred to is in the sentence before.

My response: So, put a reference ([12]) after that sentence. 

 

2.  

Lines: 276-279. Changes in that sentence are acceptable partially. No one cares about producing vaccines before a target is known. If sth is unlikely (to identify the prevalence among all of the 570 unique tribes in the US), probability of funding is very low. Maybe broad-spectral (against a consensus element of each type of HPV) vaccines are probable, but I’m not someone who can answer this question. The manuscript is not about personalized vaccines, now it seems to be about nothing. Nevertheless, it is the essence of your entire manuscript. Therefore some additional changes are necessary, otherwise I will not accept Your article. Some suggestions, some discussions, whatever, but more than wishes, should be placed there, if you are not interested in HPV-PCR testing. It is not Scientific American, it should not be a popular science article. ‘Inclusive’ in the title seems to be a good idea.

Author Response

Dear Reviewer 1,

Thank you for your quick response. We have made the suggested edits to the minor and major comments.

Minor comment 1: Add reference ([12]) after that sentence in. (line 102)

Response: The system reformatted the assigned lines. The new lines are now 76-77 and reads as “In a meta-analysis study of women, the most prevalent hrHPV types were reported globally and by continent [12].”

Major comment 1: Lines: 276-279. Changes in that sentence are acceptable partially. No one cares about producing vaccines before a target is known. If this is unlikely (to identify the prevalence among all of the 570 unique tribes in the US), probability of funding is very low. Maybe broad-spectral (against a consensus element of each type of HPV) vaccines are probable, but I’m not someone who can answer this question. The manuscript is not about personalized vaccines, now it seems to be about nothing. Nevertheless, it is the essence of your entire manuscript. Therefore, some additional changes are necessary, otherwise I will not accept Your article. Some suggestions, some discussions, whatever, but more than wishes, should be placed there, if you are not interested in HPV-PCR testing. It is not Scientific American, it should not be a popular science article. ‘Inclusive’ in the title seems to be a good idea.

Response: In Revision 1, lines 276-279 stated " The most prevalent hrHPV types in cervical cancers among Native American women has not been well studied, however two studies suggest that other hrHPV genotypes not represented in the current FDA-approved vaccines are found frequently in these populations [7, 13].” However, in the original document, we addressed “comment 7: 3.2, line 288-290; ‘The most prevalent hrHPV types in cervical cancers among Native American women is unknown. Therefore, future HPV vaccines must provide broader coverage for types not found in the general population’. No, therefore hrHPV prevalence among Native American women should be studied.”

Regardless, we agree that further research is needed prior to producing new vaccines. Therefore, we have revised lines 264-267 to read “Otherwise, vaccines designed for the general population may not be as efficacious in populations excluded from the clinical trials – as suggested by the prevalence of hrHPV types among two Native American tribes not included in the current FDA approved vaccine (Figure 1). Additional studies of the prevalence of hrHPV types among other Native American tribes are warranted and may inform future vaccine development.”

As for your comment about a consensus sequence, we agree and that is the target for our ongoing lab-based research but not published at this time. Therefore, we also included the statement (lines 282-283), “For example, coverage against HPV-51 – as it is the most prevalent in two geographically separated Native American tribes (Figure 1) [7, 13].”

Round 3

Reviewer 1 Report

Dear Authors,

Thank You for your recent revision. 

What a pity, that there is nothing about a consensus sequence, when it is under your ongoing lab-based research. What a pity.

Now, I can accept the whole manuscript.

Greetings from Europe.