Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This article explores the association between incense and mosquito coil burning and the risk of nasopharyngeal cancer, which has public health significance. There are some polishments need to be done.

1. In this study, the authors included couples of studies carried out by Yu. et.al, they have simiar resluts. Therefore, so these results are consistently insignificant. But the final analysis for all the included studies is significant. The authors need to specify this.
2. In this study, the authors included both cohort and case-control studies, but there resluts are not consistent. So, how to compare them together?
3.  Title"Domestic Burning of Incense and Mosquito Coils on the Risk of Nasopharyngeal Carcinoma: Systematic Review and Meta- Analysis" need to be revised, because all data included were from Chinese participants.
4.  A meta-analysis of mosquito coil combustion during the adult period showed high heterogeneity (I²=80%, P=0.002). The conclusion was limited in reliability as only sensitivity analysis excluding individual studies was performed, without subgroup analysis (such as stratification by population, exposure assessment methods, or degree of confounding adjustment) or meta-regression to explore the source of heterogeneity.
5.  Althouth the authors found "increased risk of NPC associated with incense burning during both adulthood and childhood periods and mosquito coils burning during adulthood", they are too limted that more studies need to be included.
6.  Only 1 out of 12 case-control studies considered exposure intensity and duration;most merely categorized exposure as 'exposed' or 'unexposed' without discussing potential OR value dilution (or overestimation) due to non-differential misclassification. Besides, only 4 case-control studies adjusted for confounding factors (such as smoking, diet). Since salted fish consumption is a known risk factor for nasopharyngeal carcinoma, failure to adjust for it may also lead to residual confounding, which should be explicitly addressed in the discussion.
7.  There are also  many format issues in the manuscript, such as 3.., why two dots?

Author Response

Reviewer 1

This article explores the association between incense and mosquito coil burning and the risk of nasopharyngeal cancer, which has public health significance. There are some polishments need to be done.

1. In this study, the authors included couples of studies carried out by Yu. et.al, they have simiar resluts. Therefore, so these results are consistently insignificant. But the final analysis for all the included studies is significant. The authors need to specify this.

 

Response:

Thank you for your valuable comments.

Thank you very much for this comment. We agree with the reviewer that the studies by Yu et al. consistently showed non-significant associations. In the pooled analysis, however, these studies had relatively limited weight (e.g., 12.8% weight for incense burning during adulthood) because of their modest sample size and therefore contributed less to the overall summary estimate. Meta-analysis increases statistical power by combining evidence across studies. In addition, heterogeneity in population characteristics, exposure assessment (including potential misclassification), control of potential confounding, and random error may also explain the difference between individual study findings and the pooled summary estimate. We have elaborated exposure assessment in the previous studies in 4^th paragraph of the Discussion section. Specifically, we highlighted that potential exposure misclassification, particularly if non-differential, in previous studies might have diluted the associations. We have also addressed other methodological issues in detail in the last paragraph of the Discussion section.

To better clarify the inconsistency between previous studies and the pooled estimates, we have added the following text in the revised manuscript: “The inconsistency between findings from previous studies and the pooled estimates may be explained by differences in study design, population characteristics, exposure assessment, control of potential confounding, and chance” (3^nd paragraph, Discussion).

 

2. In this study, the authors included both cohort and case-control studies, but there resluts are not consistent. So, how to compare them together?

Response:

We acknowledge that the included studies consisted predominantly of case–control studies, whereas only one cohort study was available. We therefore combined all studies in the primary meta-analysis. We agree that study design differences may contribute to heterogeneity. To examine the robustness of our findings, we conducted a sensitivity analysis excluding the cohort study, and the pooled associations remained materially unchanged (Supplementary Figure 3).

 

3. Title"Domestic Burning of Incense and Mosquito Coils on the Risk of Nasopharyngeal Carcinoma: Systematic Review and Meta- Analysis" need to be revised, because all data included were from Chinese participants.

Response:

We acknowledge that most included studies were conducted in regions where the majority of participants were of Chinese ethnicity. However, the included studies were not all limited to Mainland China; they were conducted in several different NPC-endemic regions including Hong Kong, Taiwan, Singapore, and the Philippines. Domestic incense and mosquito coil burning are common traditional practices across multiple Asian populations, not exclusively within China. For this reason, we consider the current title still appropriate to describe the exposure of interest, as it refers to domestic burning practices rather than a specific ethnic group or geographic region.

 

4. A meta-analysis of mosquito coil combustion during the adult period showed high heterogeneity (I²=80%, P=0.002). The conclusion was limited in reliability as only sensitivity analysis excluding individual studies was performed, without subgroup analysis (such as stratification by population, exposure assessment methods, or degree of confounding adjustment) or meta-regression to explore the source of heterogeneity.

Response:

Thank you for highlighting this. We agree that heterogeneity was high for the adult-period mosquito coil analysis (I²=80%). We considered subgroup analyses and meta-regression; however, the number of eligible studies was small, i.e., below widely recommended thresholds for credible exploration of heterogeneity. Authoritative guidance (e.g., Cochrane Handbook) advises that meta-regression and related subgroup explorations generally require at least ~10 studies to yield interpretable and adequately powered results; with fewer studies, such analyses are prone to spurious or unstable findings and low power. Therefore, we prespecified and conducted leave-one-out sensitivity analyses to assess robustness, and we interpret the pooled estimate cautiously. We have now made this rationale explicit in the revised manuscript as follows: “Given the small number of studies available for the adult-period mosquito coil analysis, we did not perform subgroup analyses or meta-regression to investigate heterogeneity” (last paragraph, Methods section).

 

5. Althouth the authors found "increased risk of NPC associated with incense burning during both adulthood and childhood periods and mosquito coils burning during adulthood", they are too limted that more studies need to be included.

Response:

We agree with the reviewer that the number of eligible studies on this topic is still limited. This is also reflected in the overall width of confidence intervals and our cautious interpretation. Our findings therefore need to be interpreted as the best available summary of currently published evidence, rather than definitive conclusions. Nevertheless, we have further emphasised the need for more epidemiological studies with improved exposure assessment and larger sample sizes in the Conclusions.

 

6.  Only 1 out of 12 case-control studies considered exposure intensity and duration; most merely categorized exposure as 'exposed' or 'unexposed' without discussing potential OR value dilution (or overestimation) due to non-differential misclassification. Besides, only 4 case-control studies adjusted for confounding factors (such as smoking, diet). Since salted fish consumption is a known risk factor for nasopharyngeal carcinoma, failure to adjust for it may also lead to residual confounding, which should be explicitly addressed in the discussion.

Response:

We agree that most case-control studies only classified exposure as “exposed” vs. “unexposed” and did not quantify exposure duration or intensity, which may have introduced non-differential exposure misclassification and biased risk estimates towards the null. Indeed, only one study (conducted by our research team) assessed both exposure duration and frequency. Failure to sufficiently adjust for potential confounders was also a major concern in previous studies. We have already elaborated these methodological limitations in separate paragraphs in the Discussion, and therefore, no further changes have been made to the manuscript.

 

7. There are also many format issues in the manuscript, such as 3.., why two dots?

Response:

Thank you very much for pointing this out. We appreciate the reviewer’s careful reading. We have carefully checked the entire manuscript and corrected all formatting issues, including removal of double periods (e.g., “3..”), spacing, punctuation inconsistencies, and typographical errors.

Reviewer 2 Report

Comments and Suggestions for Authors

This paper is a literature review on the impact of burning incensce and mosquito coils on the risk of nasopharyngeal cancer. This topic is interesting because in many regions of the world, these devices / items are used for cultural, religious, or insecticide reasons. Combustion products can pose a significant health risk to indoor users, especially with long-term, chronic exposure.

 

Therefore, this topic is important and worth presenting to a wider audience.

The text is structured in a typical review paper. The terminology is correct.

 

Notes:

1. The Introduction requires emphasizing which substances other than PAHs are found in the smoke from burning incense and mosquito coils; The novelty should be emphasized more and the research gap should be indicated.
2. Methods

- I suggest removing the subsection titles; they add nothing valuable to the text.

- Describe in more detail which journal databases were used and why these and not others.

- What were the exact keywords or phrases used in the bibliographic search?

- What were the exclusion criteria.

3. Results

- If, out of 507 potential articles, 496 were deemed irrelevant, the question arises as to whether the criteria and keywords were adopted correctly?

4. Discussion

- page 9, the second paragraph should be moved to the introduction.

- this is definitely not a discussion; it's more of a summary.

- limitations should be indicated.

5. References - Check the accuracy of the authors and the completeness of the titles. For example, Ref. 26 has an incomplete title.

The text's editing page requires thorough revision.

In my opinion, only 12 papers cannot constitute a reliable review. I understand that the authors attempted to narrow the search criteria as much as possible to meet the criteria proposed in section 2.2. However, this leaves us without a broader picture of the scale of the problem. The source papers date from 1973 to 2014, with studies from the 1980s dominating. Over the years, methods of diagnosing diseases and conducting epidemiological studies have changed, and additional environmental factors that can cause nasopharyngeal cancer have emerged. The 12 selected papers do not provide a complete scale of the problem; on the contrary, they distort its presentation for case studies. A better solution would be to broaden the search criteria.

Comments on the Quality of English Language

Lingustic correction is recommended.

Author Response

Reviewer 2

This paper is a literature review on the impact of burning incensce and mosquito coils on the risk of nasopharyngeal cancer. This topic is interesting because in many regions of the world, these devices / items are used for cultural, religious, or insecticide reasons. Combustion products can pose a significant health risk to indoor users, especially with long-term, chronic exposure.

Therefore, this topic is important and worth presenting to a wider audience.

The text is structured in a typical review paper. The terminology is correct.

Response:

Thank you very much for your positive evaluation and encouraging comments. We appreciate your recognition of the importance of this topic and the relevance of presenting these findings to a wider scientific audience.

 

Notes:

1. The Introduction requires emphasizing which substances other than PAHs are found in the smoke from burning incense and mosquito coils; The novelty should be emphasized more and the research gap should be indicated.

Response:

We agree that incense and mosquito coil combustion releases multiple harmful substances beyond PAHs. We have already mentioned some suspected carcinogens such as formaldehyde and benzene in the Introduction. 

Previous studies on this topic reported inconsistent findings. Our study uniquely addresses this gap by statistically combining available evidence and evaluating methodological limitations of previous studies. We have now clarified this as follows in the manuscript: “To clarify such associations and explore reasons underlying such inconsistency, we con-ducted this systematic review of available epidemiological evidence with a comprehensive literature search, quality assessment and a statistical synthesis of available evidence. Needs for future research in light of the methodological issues in previous studies are also discussed hereby” (last paragraph, Introduction section).

 

2. Methods

- I suggest removing the subsection titles; they add nothing valuable to the text.

- Describe in more detail which journal databases were used and why these and not others.

- What were the exact keywords or phrases used in the bibliographic search?

- What were the exclusion criteria.

Response:

We appreciate your view and we fully considered removing the subsection subtitles. However, given the complexity of the exposure domains and time windows covered in this review, we believe that keeping the subtitles helps guide readers through the narrative synthesis more clearly and improves the structure and readability of the text. Subsection titles are commonly used in systematic reviews to assist readers in following the logic of evidence synthesis. Therefore, we respectfully prefer to keep the subtitles in the current version.

We conducted a comprehensive search in MEDLINE and Embase through Ovid. These two databases were selected because they are the most widely used major biomedical literature databases and are considered the core sources for epidemiological and clinical research, and together provide the broad and complementary coverage of global biomedical publications. We have now clarified this rationale as follows in the revised manuscript: “A comprehensive search of studies published through October 2024 in MEDLINE and Embase databases was performed through the interface provided by Ovid with no language restriction. These two databases were selected because they are the most widely used major biomedical literature databases, and are considered the core sources for epidemiological and clinical research, providing broad and complementary global coverage of the biomedical literature” (2^nd paragraph, Methods section).

The exact key words used in literature search are provided in Supplementary Table 1.

In this systematic review, studies that fulfilled all pre-specified inclusion criteria were included. We did not apply additional exclusion criteria beyond these eligibility criteria. We have now clarified this explicitly in the revised manuscript as follows to avoid misunderstanding: “” (3^rd paragraph, Methods section).

 

3. Results

- If, out of 507 potential articles, 496 were deemed irrelevant, the question arises as to whether the criteria and keywords were adopted correctly?

Response:

We agree that the number of initially identified records was large compared with the number finally included. This is expected because we intentionally applied a broad search strategy in order to maximise sensitivity and avoid missing any eligible studies. Most of the initially retrieved articles were screened out at title/abstract level because they did not address incense or mosquito coil burning on the risk of nasopharyngeal carcinoma, or were not epidemiological studies evaluating onset of nasopharyngeal carcinoma as an outcome. Therefore, the high number of exclusions mainly reflects the specificity of our research question, rather than an inappropriate choice of search terms.

 

4. Discussion

- page 9, the second paragraph should be moved to the introduction.

- this is definitely not a discussion; it's more of a summary.

- limitations should be indicated.

Response:

We appreciate your view. The purpose of the first paragraph of the Discussion was to briefly summarise the main findings before presenting interpretation, explanation and implications in subsequent paragraphs. This structure is commonly used in many journals to orient readers at the beginning of the Discussion section. Therefore, we respectfully prefer to retain this introductory summary paragraph as the opening part of the Discussion.

The limitations, including potential risk of selection bias and influence from primary studies have been discussed in the two last paragraphs of the Discussion section.

 

5. References - Check the accuracy of the authors and the completeness of the titles. For example, Ref. 26 has an incomplete title.

Response:

We sincerely appreciate your careful review of the reference list. We have now thoroughly checked all references for accuracy, including authors’ names, publication years, journal titles, and the completeness of article titles. We have corrected the incomplete title for Reference 26 and any other inconsistencies identified during the check.

 

The text's editing page requires thorough revision.

Response:

We have now thoroughly revised the entire manuscript for language clarity, grammar, punctuation, and formatting consistency.

 

In my opinion, only 12 papers cannot constitute a reliable review. I understand that the authors attempted to narrow the search criteria as much as possible to meet the criteria proposed in section 2.2. However, this leaves us without a broader picture of the scale of the problem. The source papers date from 1973 to 2014, with studies from the 1980s dominating. Over the years, methods of diagnosing diseases and conducting epidemiological studies have changed, and additional environmental factors that can cause nasopharyngeal cancer have emerged. The 12 selected papers do not provide a complete scale of the problem; on the contrary, they distort its presentation for case studies. A better solution would be to broaden the search criteria.

Response:

Thank you very much for this thoughtful and important comment. We fully agree that the number of eligible studies is limited and that this restricts the strength of conclusions that can be drawn. However, the small number of studies reflects the current state of published epidemiological evidence rather than an overly narrow search strategy. We applied broad search terms and no language restriction in both MEDLINE and Embase databases to capture all potentially relevant studies. After careful screening, only one cohort study and 12 case-control studies fulfilled the predefined eligibility criteria, namely, original epidemiological investigations assessing incense or mosquito coil burning in relation to nasopharyngeal carcinoma risk.

We also acknowledge that most studies were conducted between the 1980s and early 2010s. These limitations have been explicitly discussed in the Discussion section. We have now added the short following statements to further emphasise that the limited number and age of available studies reflect a major research gap that future studies should address: “Notably, the limited number of eligible studies, most of which were conducted several decades ago, reflects the current scarcity of epidemiological research on this topic. This highlights a substantial research gap and the need for updated, large-scale studies using contemporary study design and exposure assessment methods” (last paragraph, Discussion).

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors' revisions in response to the initial review comments have improved the quality of the manuscript. To further enhance the rigor and readability of the paper, following minor suggestions:

1. I accept the authors' rationale for retaining the current title. However, to ensure readers accurately understand the applicability of the evidence from the outset, I suggest adding a statement in the Discussion section noting that "the evidence included in this meta-analysis was primarily derived from studies conducted in East Asian and Southeast Asian populations."
2. Salted fish consumption is a well-established and important risk factor for nasopharyngeal carcinoma. To ensure this critical point is not obscured in the general discussion of "potential confounding factors," please explicitly identify "salted fish consumption" as a key example of a residual confounding factor that may not have been adequately adjusted for in the paragraph discussing relevant limitations.
3. There are still formatting issues throughout the manuscript, such as 4.. and 5.., why two dots？

Author Response

Please refer to the attached responses.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

I would like to thank the authors for responding to the reviewer's suggestions and comments. The changes to the text can be described as symbolic. Therefore, the new version of the manuscript does not differ significantly from the first. I understand the authors' position that they wanted to limit the number of works on which they based their review. However, in my opinion, this is not the correct approach. Such a small number of references limits the true state of knowledge on this topic.

Author Response

Please refere to the attached responses.

Author Response File: Author Response.pdf