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. 2022 Mar 17;17(3):e0265543. doi: 10.1371/journal.pone.0265543

Investigation of the incidence trend of follicular lymphoma from 2008 to 2017 in Taiwan and the United States using population-based data

Yu-Chieh Su 1,2, Brian Chih-Hung Chiu 3, Hung-Ju Li 1, Wen-Chi Yang 1,2, Tsai-Yun Chen 4, Su-Peng Yeh 5,6, Ming-Chung Wang 7, Wen-Tsung Huang 8, Ming-Yang Lee 9, Sheng-Fung Lin 1,*
Editor: Carla Pegoraro10
PMCID: PMC8929617  PMID: 35298555

Abstract

Background

The incidence of follicular lymphoma (FL) in Taiwan has not been well investigated since its inclusion as a histological subtype in the Taiwan Cancer Registry in 2008. The purpose of this study was to describe the incidence patterns of FL in Taiwan and compare the trends with those in other racial groups in the United States.

Materials and methods

We conducted an epidemiological study using population-based data from the Taiwan Cancer Registry, Ministry of Health and Welfare, and the 18 Surveillance, Epidemiology, and End Results (SEER) registries to evaluate the FL incidence from 2008 to 2017. We calculated the annual percent change (APC) to describe the trends in the incidence of FL in subpopulations defined by race and sex over time.

Results

The annual age-adjusted incidence rate of FL in Taiwan increased significantly from 0.59 per 100,000 persons in 2008 to 0.82 per 100,000 persons in 2017, with an APC of 3.2. By contrast, the incidence rate in whites in the United States during the same period decreased from 3.42 to 2.74 per 100,000 persons, with an APC of −2.1. We found no significant change for the blacks (APC, −1.5%), Hispanics (APC, −0.7%), and Asians or Pacific Islanders (APC, +0.7%). The temporal trend was similar between the males and females. The relative frequency of FL among the incident non-Hodgkin lymphoma (NHL) cases also increased significantly in Taiwan from 7.64% in 2008 to 11.11% in 2017 (APC = 3.8). The relative frequency of FL among the incident NHL cases in the whites decreased from 2008 to 2012 (APC, −3.8%) and then stabilized after 2012 (APC, −0.2%). By contrast, little change in relative frequency of FL among the incident NHL cases was observed in the blacks, Hispanics, and APIs between 2008 and 2017.

Conclusion

We found increases in the incidence of FL and the relative frequency of FL among the incident NHL cases in both males and females in Taiwan from 2008 to 2017. The FL incidence rates were unchanged for all races and sex groups in the United States, except for the decreases in the whites.

Introduction

Follicular lymphoma (FL) is one of the most common subtypes of non-Hodgkin lymphoma (NHL) in the United States (US), with an incidence rate of 3·5 per 100,000 persons per year in 2008–2017 and representing 12·4% of all mature NHLs [1]. FL accounted for a higher percentage of NHLs in the United States and Western countries than in Asia [2–5]. However, evidence is accumulating that the FL incidence rate has been increasing in certain Asian countries. The proportion of FLs in Japan increased from 18·3% in 2000–2006 to 22·4% in 2007–2014 [6]. Chihara et al. showed that the world age-standardized incidence rates of FL in Japan increased from 0·1 to 1·1 per 100,000 persons between 1993 and 2008 [7]. A similar upward trend was also observed in South Korea during the 1999–2015 period [8, 9] (from 0·2 to 0·6 per 100,000 persons) and in Taiwan from 1990 to 2012 (from 0·3 to 0·9 per 100,000 persons) [10, 11].

Intensive epidemiological research, including those from the International Lymphoma Epidemiology Consortium (InterLymph), has provided intriguing new insights into the possible risk factors of FL, such as anthropometrics, family history of NHL, genetic susceptibility, pesticide use, and alcohol use [4, 12, 13]. However, the geographic heterogeneity of the incidence of FL and the upward trend in some Asian countries are widely recognized but remain largely unexplained. In addition, the increasing proportion of FLs in NHLs, approaching to that in Western countries in some regions [7, 14] but not in other regions [15, 16] in Asia remains incompletely understood. Additional evaluation of the incidence patterns in Asia using population-based registries is needed to provide leads and information for formulating etiological hypotheses.

We therefore analyzed Taiwanese and US population-based data on FL from the Taiwan Cancer Registry (TCR) and the US National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, respectively. As FL was not reported as a subtype in the TCR until 2008 [17], we limited our analysis to the period from 2008 to 2017, the most recent period with available complete data.

Materials and methods

Study purpose

The objective of this study was to describe the incidence patterns of FL in Taiwan and compare the trends with those in other racial groups in the US.

Patient population

We obtained FL cases in Taiwan for the period 2008–2017 from the TCR annual report of the Health Promotion Administration, Ministry of Health and Welfare, Taiwan [17] (S1 Table in S1 File). The data of FL cases in US for the study period of 2008–2017 was using the US National Cancer Institute’s SEER 18 program for the period 2008–2017 [18] (S1 Table in S1 File).

Data quality and completeness

The annual population was obtained from the Department of Household Registration, Ministry of the Interior, Taiwan [19] (S1 Table in S1 File). The cancer registry annual report based on the databased established by the TCR which case completeness rates increased from 97·6% in 2008 to 98·3% in 2017 [17, 20]. The TCR implemented rigorous quality control protocols to validate and verify cancer diagnoses, including submission of tissue pathology reports and random sampling of claims and diagnosis reports. It is considered a complete and accurate registry [21]. All information on the primary cancer site and histology was coded in accordance with the third edition of the International Classification of Diseases for Oncology (ICD-O-3). FL was added as a distinct lymphoma subtype to the TCR in 2008, in accordance with the 2008 revision of the World Health Organization classification [17]. Other routinely reported common subtype categories include diffuse large B-cell lymphoma, marginal zone lymphoma, peripheral T-cell lymphoma, and extranodal NK/T-cell lymphoma [17].

The SEER registries covered approximately 35% of the US population. For each newly identified case, SEER registries report patient demographic data, including age, race, ethnicity, and sex, and information on the tumor histological type, primary site, and stage at diagnosis. The SEER program records race as assigned by the North American Association of Central Cancer Registries, which is only comprehensive source of population-based in the US and have a case completeness rate greater than 98% [22].

Data analysis

The SEER racial groups included non-Hispanic whites (hereafter referred to as whites), Hispanic whites (hereafter referred to as Hispanics), non-Hispanic blacks (hereafter referred to as blacks), and Asians/Pacific Islanders (APIs). Owing to the low numbers of cases, we did not include American Indians/Alaskan Natives in the present analysis.

Patients with FLs were identified using the International Classification of Disease for Oncology, Third Edition (ICD-O-3; Histology codes: 9690, 9691, 9695, and 9698) [23]. The incidence rates and relative frequencies of FL were calculated for FL overall and according to sex and racial groups as follows: Taiwanese (TWs), whites, Hispanics, blacks, and APIs. The age-adjusted incidence rates were standardized to the 2000 world standard population [24].

The incidence rates and relative frequency of FL among the incident NHL cases were calculated using SPSS version 24.0 (released 2016, IBM SPSS Statistics for Windows, Version 24.0, IBM Corp., Armonk, NY) and SEER*Stat software, Version 8.3.8 (Surveillance Research Program, National Cancer Institute) [25]. Temporal trends for the age-adjusted incidence rates and relative frequency of FL among the incident NHL cases from 2008 to 2017 were characterized by the annual percent change (APC) and 95% confidence intervals by using the weighted least squares method in the Joinpoint Regression Program, Version 4.8.0.1 (NCI Statistical Methodology and Applications Branch, Bethesda, MD) [26, 27]. APC is often used to characterize trends in disease rates, which assume the disease rates change at a constant percentage of the rate of the previous year by using this approach. The Joinpoint Regression Program described the change of data trend by several connected line segments on a logarithmic scale with turning points or “joinpoints.” The program used the permutation test to find the number of significant joinpoints. If no joinpoint was detected, it presented the data trend as a straight line with a single APC. When two or more joinpoints were detected, the program showed the corresponding APC for each line segment (time period) and the year of the joinpoint. The trend between males and females was compared by using a test of parallelism. An independent two-sided t test was used to determine if the APC was statistically significant from 0. The statistical significance of the differences was assessed at a p value < 0·05.

Results

From 2008 to 2017, 2,494 FL cases were reported to the TCR in Taiwan. Of the patients, 1,279 (51·3%) were males. During the same period, 27,611 patients with FL were reported to the 18 SEER registries, including 24,517 whites, 1,494 blacks, 3,956 Hispanics, and 1,600 APIs, of whom 12,486 (50·9%), 716 (47·9%), 1,848 (46·7%), and 826 (51·6%) were males, respectively.

Figs 1 and 2 show the world age-adjusted incidence rates of FL and the relative frequency of FL among the incident NHL cases for FL overall and stratified by sex according to race. The APCs and 95% confidence intervals (CIs) are listed in Table 1. The incidence of FL increased significantly from 0·59 to 0·82 per 100,000 person-years between 2008 and 2017 in Taiwan, representing a 39% increase and an APC of 3·2% (95% CI: 1·6%–4·8%). The upward trend in FL incidence occurred in both the males and females. The incidence rate increased by 2·6% (95% CI: 0·3%–5·0%) per year from 0·64 to 0·81 cases per 100,000 person-years in the males and by 3·8% (95% CI: 1·4%–6·3%) per year from 0·54 to 0·85 cases per 100,000 person-years in the females. By contrast, the incidence rates declined by −2·1% (95% CI: −2·9% to −1·2%) per year in the whites, from 3·42 to 2·74 per 100,000 person-years between 2008 and 2017, representing a 20% decrease. For the white males and females, the incidence rates decreased significantly by −1·8% (95% CI: −2·9% to −0·7%) and −2·4% (95% CI: −3·1% to −1·7%) per year from 3·75 to 3·00 per 100,000 person-years and from 3·11 to 2·50 per 100,000 person-years, respectively. The tests of parallelism for the male and female trend lines in the Taiwanese population and US white population both were not significant (p = 0.456 and 0.133). During the same period, no significant changes in the age-adjusted incidence rates were found in the blacks, Hispanics, and APIs, regardless of sex, as shown in Table 1.

Fig 1. Trends in the world age-adjusted incidence rate according to racial group for the period 2008–2017.

Fig 1

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(A) Overall. (B) Males. (C) Females. *The APC is significantly different from 0 at the alpha level of 0.05.

Fig 2. Trends in the relative frequency of FL among the incident NHL cases according to racial groups for the period 2008–2017.

Fig 2

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(A) Overall. (B) Males. (C) Females. *The APC is significantly different from 0 at the alpha level of 0.05.

Table 1. Number of follicular lymphoma cases and trends in age-adjusted rates and relative frequency of FL among the incident NHL cases according to sex for the period 2008–2017.

Year
Total 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 APC (95% CI) p
TWs
Total Cases 2494 169 205 226 238 249 239 263 290 319 296
IR 0.77 0.59 0.69 0.75 0.76 0.77 0.74 0.77 0.83 0.91 0.82 3.2* (1.6, 4.8) 0.002
RF (%) 10.5 7.6 7.8 10.9 11.4 10.9 10.2 10.6 11.3 12.9 11.1 3.8* (0.9, 6.8) 0.017
Males Cases 1279 91 115 104 123 136 130 127 145 169 139
IR 0.81 0.64 0.79 0.71 0.80 0.85 0.82 0.76 0.85 0.99 0.81 2.6* (0.3, 5.0) 0.032
RF (%) 9.5 7.1 7.8 8.8 10.6 10.7 9.9 9.2 10.2 12.1 9.3 3.4* (0.1, 6.8) 0.047
Females Cases 1215 78 90 122 115 113 109 136 145 150 157
IR 0.73 0.54 0.60 0.79 0.73 0.69 .66 0.77 0.82 0.83 0.85 3.8* (1.4, 6.3) 0.006
RF (%) 11.7 8.5 7.9 13.5 12.3 11.2 10.6 12.5 12.7 14.0 13.4 4.2* (0.6, 7.9) 0.028
whites
Total Cases 24517 2609 2525 2574 2391 2357 2322 2522 2430 2471 2316
IR 3.03 3.42 3.26 3.30 3.02 2.96 2.84 3.01 2.92 2.92 2.74 −2.1* (−2.9, −1.2) 0.001
RF (%) 11.5 12.9 12.4 12.2 11.4 11.0 10.8 11.4 10.9 11.3 10.7 −3.8* (−6.6, −0.9) (Year 08−12) −0.2 (−2.4, 2.0) (Year 12–17) 0.021
0.796
Males Cases 12486 1320 1239 1297 1179 1210 1197 1330 1264 1251 1199
IR 3.30 3.75 3.44 3.58 3.20 3.21 3.09 3.37 3.22 3.18 3.00 −1.8* (−2.9, −0.7) 0.006
RF (%) 10.2 11.6 10.7 10.9 9.9 9.8 9.6 10.4 9.8 9.8 9.6 −1.6* (−2.6, −0.6) 0.007
Females Cases 12031 1289 1286 1277 1212 1147 1125 1192 1166 1220 1117
IR 2.80 3.11 3.10 3.05 2.87 2.75 2.62 2.70 2.66 2.68 2.50 −2.4* (−3.1, −1.7) <0.001
RF (%) 13.2 14.6 14.8 13.9 13.4 12.7 12.4 12.9 12.4 13.2 12.2 −1.9* (−2.8, −0.9) 0.002
blacks
Total Cases 1494 135 157 150 139 154 132 151 143 181 152
IR 1.24 1.29 1.44 1.34 1.22 1.29 1.07 1.20 1.10 1.36 1.14 −1.5 (−3.7, 0.7) 0.152
RF (%) 4.9 5.3 5.7 5.3 4.7 4.9 4.2 4.8 4.5 5.3 4.6 −1.6 (−3.7, 0.6) 0.137
Males Cases 716 58 68 76 67 77 55 85 74 81 75
IR 1.35 1.26 1.38 1.51 1.31 1.48 0.98 1.56 1.31 1.39 1.26 −0.3 (−3.6, 3.0) 0.816
RF (%) 4.4 4.3 4.7 5.0 4.4 4.6 3.3 5.0 4.3 4.6 4.3 −0.5 (−3.4, 2.5) 0.709
Females Cases 778 77 89 74 72 77 77 66 69 100 77
IR 1.15 1.29 1.46 1.21 1.12 1.14 1.14 0.92 0.92 1.37 1.03 −2.4 (−5.8, 1.2) 0.163
RF (%) 5.4 6.4 6.7 5.8 5.1 5.3 5.1 4.6 4.6 6.1 4.9 −2.5 (−5.3, 0.4) 0.079
Hispanics
Total Cases 3956 336 304 397 381 390 405 403 435 435 470
IR 2.34 2.45 2.10 2.68 2.39 2.36 2.37 2.24 2.33 2.23 2.32 −0.7 (−2.3, 0.9) 0.346
RF (%) 10.5 10.7 9.4 11.5 10.7 10.6 10.8 10.0 10.6 10.1 10.9 −0.1 (−1.5, 1.4) 0.928
Males Cases 1848 141 139 196 180 188 191 173 213 204 223
IR 2.35 2.24 2.07 2.88 2.45 2.41 2.44 2.07 2.41 2.22 2.36 −0.5 (−3.0, 2.1) 0.658
RF (%) 9.0 8.3 8.1 10.2 9.4 9.2 9.1 8.0 9.8 8.6 9.6 0.5 (−1.7, 2.6) 0.636
Females Cases 2108 195 165 201 201 202 214 230 222 231 247
IR 2.35 2.67 2.12 2.53 2.35 2.31 2.34 2.40 2.26 2.26 2.31 −0.9 (−2.3, 0.6) 0.197
RF (%) 12.3 13.4 10.9 13.2 12.3 12.3 13.1 12.1 11.6 11.8 12.5 −0.5 (−2.1, 1.1) 0.466
APIs
Total Cases 1600 149 119 132 152 148 165 185 160 196 194
IR 1.35 1.52 1.17 1.22 1.35 1.28 1.38 1.51 1.22 1.49 1.38 0.7 (−1.7, 3.2) 0.699
RF (%) 8.9 9.8 7.7 8.1 8.8 8.5 9.2 9.5 8.0 9.5 9.5 0.9 (−1.2, 3.0) 0.361
Males Cases 826 84 65 63 81 76 86 95 82 96 98
IR 1.56 1.89 1.43 1.32 1.63 1.46 1.60 1.74 1.40 1.61 1.57 −0.3 (−3.0, 2.5) 0.797
RF (%) 8.4 10.0 7.8 7.1 8.7 7.6 8.8 8.9 7.5 8.7 8.8 −0.1 (−2.8, 2.6) 0.923
Females Cases 774 65 54 69 71 72 79 90 78 100 96
IR 1.18 1.22 0.98 1.13 1.12 1.14 1.20 1.30 1.07 1.39 1.23 1.7 (−0.6, 4.1) 0.125
RF (%) 9.5 9.4 7.6 9.2 9.0 9.7 9.8 10.1 8.7 10.4 10.4 1.9 (−0.1, 3.9) 0.057
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IR, World age-adjusted incidence rate; RF, relative frequency of FL among the incident NHL cases; APC, annual percent change; CI, confidence interval; TWs, Taiwanese; whites, non-Hispanic whites; blacks, non-Hispanic blacks; Hispanics, Hispanic whites; APIs, non-Hispanic Asians or Pacific Islanders. *The APC is significantly different from 0 at the alpha level of 0.05.

Fig 2 and Table 1 show the trends in the relative frequency of FL among the incident NHL cases. In Taiwan, the relative frequency of FL among the incident NHL cases increased from 7·6% to 11·1% from 2008 to 2017, with an APC of 3·8% (95% CI: 0·9%–6·8%). The relative frequency of FL among the incident NHL cases increased in both the males and females, from 7·1% to 9·3% between 2008 and 2017 (APC, +3·4%, 95% CI: 0·1%–6·8%) in the males and from 8·5% to 13·4% (APC, +4·2%, 95% CI: 0·6%–7·9%) in the females. In the whites, the relative frequency of FL among the incident NHL cases declined from 12.9% to 10.7%, the average APC was −1.8 (95% CI: −3.1% to −0.5%, p = 0.009). In the white males and females, the relative frequency of FL among the incident NHL cases declined from 11·6% to 9·6% (APC = −1·6, 95% CI: −2·6% to −0·6%) and from 14·6% to 12·2% (APC = −1·9, 95% CI: −2·8% to −0·9%), respectively. By contrast, the relative frequency of FL among the incident NHL cases remained stable during 2008–2017 among the blacks, Hispanics, and APIs, regardless of sex (Table 1).

Discussion

To the best of our knowledge, this report presents the most recent temporal trend of the incidence of FL in Taiwan. We found that the incidence of FL and the relative frequency of FL among the incident NHL cases increased significantly between 2008 and 2017 in Taiwan, and the upward trend was observed in both males and females. By contrast, during the same period, the FL incidence rate decreased in the whites and appeared to remain stable in the blacks, Hispanics, and APIs. The reasons for these differences have not been well explained to date.

The leading causes of the increasing incidence of FL in Taiwan are largely unknown. Several risk factors of FL have been suggested, including sedentary lifestyle, obesity, diet, environmental exposures, and recreational sun exposure [4, 13, 28]. Part of the lower risk of FL in Asians may be genetics [29], and several genetic loci have been identified, particularly in the human leukocyte antigen (HLA) region [30]. Genetic variants, however, are unlikely to fully explain the diverse trend of FL in different racial groups. Our findings of a significant increase in the incidence of FL from 2008 to 2017 in Taiwan suggest the importance of modifiable lifestyle and environmental factors. For example, cigarette smoking has been associated with the risk of FL in two large InterLymph pooled analyses [13, 31]. The frequency of t(14;18) translocation, which occurs in approximately 85% of FLs, is 3·6-fold higher in heavy smokers (>40 pack-years) than in nonsmokers and may explain the association between smoking and FL. However, a case-control study found no association between smoking and t(14;18)-positive NHL in men and women [32]. The dietary patterns in Taiwan are becoming increasingly westernized, featuring high meat and low vegetable consumptions. Meat intake and the components in meats (e.g., fat) have been associated with a risk of FL [33–38]. Dietary patterns high in meat and fat contents have been linked to excess FL risk in a case-control study [39], but not in two large prospective cohorts [34]. Obesity, a potential risk factor of FL [13], may also explain the upward trend of FL in Taiwan, as the prevalence of obesity has been increasing from 4·1% (1993–1996) to 6·2% (2005–2008), reaching 8·2% in 2013–2014 in Taiwan [40]. Recreational sunlight exposure was inversely associated with FL risk [13]. A recent study in Taiwan found that vitamin D deficiency in men and women was partly due to lack of sun exposure [41, 42]. Further studies are needed to evaluate the association between sun exposure and the development of FL in Taiwan. A combination of these modifiable risk factors may have contributed to the increasing FL incidence in Taiwan. Although the incidence of FL showed no significant changes in the APIs in the US, it was found to be increasing in other Asian countries such as Japan and South Korea and appeared to be increasing more in South Korea [8, 9] and Japan [7] than in Taiwan (S2 Table, S3 Table in S1 File and S1 Fig). The reasons for the increasing incidence of FL in these three Asian countries may be similar, but further research is needed.

For the incidence rates in Taiwan from 2002 to 2017, no joinpoint was detected, which suggests a steady increase in incidence over this period. The incidence rates in males and females in Taiwan continue to increase with APCs of 2·3 (95% CI: 1·3–3·4) and 4·1 (95% CI: 3·0–5·3), respectively (S3 Table in S1 File). The latest data indicated that the FL incidence rates in 2018 in Taiwan were 0·95 per 100,000 person-years for males and 1·00 per 100,000 person-years for females [17], which were within the 95% CI of APC calculated using the data from 2008 to 2017. These data suggest that the FL incidence in Taiwan may continue to increase in the near future.

The main limitation of this study is that SEER data does not cover whole US population, the incidence change in each racial population in US cannot be generalized. Another limitation of our study is that the FL data in Taiwan was retrieved from the TCR annual report, not Taiwan Cancer Registry Database. The number of FL cases by gender and age in the TCR annual report was defined by ICD-O-3 codes 9597/3, 9675/3, 9690/3, 9691/3, 9695/3, and 9698/3, that is different from the definition of FL in SEER. Although we could not know the number of cases in each ICD-O-3 codes, the ICD-O-3 code 9675/3 is not applicable since 2010. The cases with code 9597/3 were very rare in Taiwan, just one case was found in a medical center from January 1998 to December 2014 [43] and there were no case in other medical center between January 2001 and December 2010 in Taiwan [44], thus it would not affect the results in this study.

In summary, this study found that the incidence of FL increased from 2008 to 2017 in Taiwan but decreased in the whites while remaining stable in the blacks, Hispanics, and APIs in the US during the same period. The patterns were similar between the males and females. A similar upward trend was also observed in Japan and South Korea. Future etiological investigations, particularly on modifiable risk factors, in Asian countries are warranted to understand the determinants of the upward trend of the incidence of FL.

Supporting information

S1 File

(DOCX)

Click here for additional data file. (21.1KB, docx)
S1 Fig. Trends in the age-standardized incidence rates of follicular lymphoma in Taiwan, Japan, and Korea.

(TIF)

Click here for additional data file. (287.5KB, tif)

Acknowledgments

The authors would like to thank Enago (www.enago.tw) for the English language review.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

This work was supported by grant EDAHP110021 from E-Da Hospital, Taiwan. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Amir Radfar

27 Aug 2021

PONE-D-21-21835

Investigation of the incidence trend of follicular lymphoma from 2008 to 2017 in Taiwan and the United States using population-based data

PLOS ONE

Dear Dr. Su,

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Comments to the Author

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Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: For people working in cancer research, an article like this is highly valuable, because the results allow to appraise and to put into context epidemiologic as well as clinical research in this area. In addition, those data are required, if data from different countries are jointly analysed in international collaborations. Furthermore, such data are required for planning future studies on follicular lymphoma in Taiwan and other countries in Asia.

The statistical analysis is, to my knowledge, state of the art. However, the authors would improve the value of the manuscript by taking a deeper look into apparent differences in the annual percentage change between males and females as well as the analysis of age at diagnosis. The latter has not been addressed so far.

Item 1. Is the manuscript technically sound, and do the data support the conclusions?

1.

The results presented in Table 1 and Table S2 show apparent differences between males and females across the different populations. As exploratory analysis, statistical tests could be performed. For example, the difference of -1.8 in the APC between males and females in the Taiwanese population in Table S2 reveals a p-value p = 0.023, indicating a difference in the APC between males and females. This finding is in contrast to the statement that the temporal trends were similar. However, due to the explorative nature of these post-hoc analyses as well as the problem of multiple testing, possible findings have to be interpreted with caution.

2.

The SEER data show some differences across groups defined by age at diagnosis. For example, for all ethnicities, an APC of -1.9 was observed overall, while the estimates for the age groups were 8.6 for ages 0-19, -2.1 for ages 20-64 and -1.8 for ages ≥ 65. Estimates are also available for males and females. The variable age at diagnosis should also be available for the Taiwanese registry data. If so, the authors should add the estimates, as supplementary data. If data for groups by age

at diagnosis are not available, please add a note on this issue.

3.

In table S2, results from joint analysis with data from Ko et al. are presented. How were the data for Table S2 merged in order to estimate the APC? Moreover, Ko et al. count lymphoma with ICD-O-3 codes 95973 and 96753 as follicular lymphoma (Ko et al., Table 1). Did the authors consider how this discrepancy between this and their own definition of follicular lymphoma could influence the results? The authors could, for example, present the number of patients with ICD-O-3 codes 95973 and 96753 in their own data set.

Minor

1. Please provide the formal definition of the annual percentage change.

2. Please use the term “relative frequency of FL among the incident NHL cases” throughout the manuscript and in the tables and figures.

3. Please add the confidence intervals as well as the p-values to the last column of Table 1.

4. Caption to Table S2: reference number for Ko et al. should be 10 instead of 8.

5. Introduction: add the unit (per year) to the statement “incidence rate of 3·5 per 100,000 persons in 2008–2017”

6. Materials and Methods, page 7: change “race” to “race/ethnicity” in the sentence “The SEER program records race as assigned by the North American Association of Central Cancer Registries.”

7. Results, page 10: the – declining – estimates for APC in whites, all as well as males and females, should be negative, i.e. -2.1, -1.8 and -2.4.

8. Caption for figure 1: add “incidence” to the word rate.

Reviewer #2: (I) Summary

The authors of this manuscript explore recent trends in follicular lymphoma (FL) in Taiwan and United States (US) using cancer registry (Taiwan Cancer Registry and US SEER) data from 2008 to 2017 with the aim of elucidating incidence patterns in both populations. They provide recent data from both cancer registries on age-adjusted incidence rates, relative frequencies and annual percent changes (APC) of FL stratified by sex and race/ethnicity. Collected data show a steadily rising trend in FL incidence in Taiwan (+39% from 2008-17) as compared to declining incidences in US white population (-20% from 2008-17) and steady trend in Hispanic, black and Asian/Pacific Islander population. The authors discuss possible factors for changes in incidence (genetics, lifestyle, environment) and compared their newly gathered data on FL incidence to recent data from other Asian countries noting some similarities. They conclude that further etiological investigations in Asian countries are needed.

(II) Discussion of specific areas of improvement

1.) Abstract

- clear and concise, no comment

2.) Introduction

- no comment

3.) Materials and methods

- the US are ethnically quite diverse and how SEER handles ethnicity is explained in great detail, please add a short comment if ethnicity is an issue for the Taiwan Cancer Registry.

4.) Results

- 2nd paragraph, line 3: APCs and 95% CI are listed in Figures 1 and 2, while Table 1 provide only APCs, this should be corrected accordingly.

-2nd paragraph, line 5: data of % change is provided for FL incidence in Taiwan (+39%), but no similar data provided for decrease in US white population, consider adding data.

- S1 table: reference to study by Ko et al is 10 and not 8, please correct

- S1 table: data for Korea12 and 15 shown with same color and symbol making it harder to read, consider correcting

- Table 1, whites, RF (%), APC: only variable with a joint point. Discuss with your statistician if an average APC could be calculated and added in the comment under the table or consider adding a comment why there are two number as opposed to all other APCs.

5.) Discussion

- list possible limitations of this study and/or biases (for example: SEER data do not cover whole US population; incidence change in US white population cannot be generalized

(III) Other comments

- very fluent reading, carefully edited text, no language issues.

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2022 Mar 17;17(3):e0265543. doi: 10.1371/journal.pone.0265543.r002

Author response to Decision Letter 0

7 Oct 2021

Revierwer #1:

Question 1.

The results presented in Table 1 and Table S2 show apparent differences between males and females across the different populations. As exploratory analysis, statistical tests could be performed. For example, the difference of -1.8 in the APC between males and females in the Taiwanese population in Table S2 reveals a p-value p = 0.023, indicating a difference in the APC between males and females. This finding is in contrast to the statement that the temporal trends were similar. However, due to the explorative nature of these post-hoc analyses as well as the problem of multiple testing, possible findings have to be interpreted with caution.

Answer: Thank you for your valuable opinions. We have provided it and marked it. (page 9, 10)

page 9: (Materials and Methods) The trend between males and females was compared by using a test of parallelism.

page 10: (Results) The tests of parallelism for the male and female trend lines in the Taiwanese population and US white population both were not significant (p = 0.456 and 0.133).

Question 2.

The SEER data show some differences across groups defined by age at diagnosis. For example, for all ethnicities, an APC of -1.9 was observed overall, while the estimates for the age groups were 8.6 for ages 0-19, -2.1 for ages 20-64 and -1.8 for ages ≥ 65. Estimates are also available for males and females. The variable age at diagnosis should also be available for the Taiwanese registry data. If so, the authors should add the estimates, as supplementary data. If data for groups by age at diagnosis are not available, please add a note on this issue.

Answer: The estimates had added in supplementary data, S3 Table. The APCs were 4.4 for ages 0-34, 2.6 for ages 35-64 and 4.0 for ages ≥ 65. For males, the APCs were 1.6, 2.7 and 2.9 for ages 0-34, 35-64, and ≥ 65, respectively. For females, the APCs were 8.2, 2.5 and 5.5 for ages 0-34, 35-64, and ≥ 65, respectively.

Because the numbers of FL cases were almost zero for ages < 30 from 2008 to 2017, we stratified the cases into 3 age groups: 0-34, 35-64, and ≥ 65.

Question 3.

In table S2, results from joint analysis with data from Ko et al. are presented. How were the data for Table S2 merged in order to estimate the APC? Moreover, Ko et al. count lymphoma with ICD-O-3 codes 95973 and 96753 as follicular lymphoma (Ko et al., Table 1). Did the authors consider how this discrepancy between this and their own definition of follicular lymphoma could influence the results? The authors could, for example, present the number of patients with ICD-O-3 codes 95973 and 96753 in their own data set.

Answer: The age-standardized incidence rates (ASR) between 2002 and 2007 from Ko et al. (Table 2) and the ASR between 2008 and 2017 from our data were merged to estimate the APC by using the Jointpoint regression under the “constant variance assumption”.

The ICD-O-3 code 9675/3 is not applicable since 2010. The cases with code 9597/3 were very rare in Taiwan, just one case was found in a medical center from January 1998 to December 2014 [1] and there were no case in other medical center between January 2001 and December 2010 in Taiwan [2], thus it would not affect the results in this study.

Reference:

1. Liu KL, Tsai WC, Lee CH. Non-mycosis fungoides cutaneous lymphomas in a referral center in Taiwan: A retrospective case series and literature review. PLoS One. 2020;15(1): e0228046. doi: 10.1371/journal.pone.0228046. PMID: 31978091.

2. Lee CN, Hsu CK, Chang KC, Wu CL, Chen TY, Lee JY. Cutaneous lymphomas in Taiwan: A review of 118 cases from a medical center in southern Taiwan. Dermatologica sinica. 2018; 36(1): 16-24. Doi: 10.1016/j.dsi.2017.08.004.

Minor Questions:

1. Please provide the formal definition of the annual percentage change.

Answer: We have provided it and marked it.

Page 8: APC is often used to characterize trends in disease rates, which assume the disease rates change at a constant percentage of the rate of the previous year by using this approach.

2. Please use the term “relative frequency of FL among the incident NHL cases” throughout the manuscript and in the tables and figures.

Answer: We have corrected it and marked it throughout the manuscript and in the tables and figures.

3. Please add the confidence intervals as well as the p-values to the last column of Table 1.

Answer: We have corrected it and marked it.

4. Caption to Table S2: reference number for Ko et al. should be 10 instead of 8.

Answer: We have corrected it and marked it for reference number in Supporting Information.

5. Introduction: add the unit (per year) to the statement “incidence rate of 3·5 per 100,000 persons in 2008–2017”

Answer: We have corrected it and marked i: incidence rate of 3·5 per 100,000 persons per year in 2008–2017

6. Materials and Methods, page 7: change “race” to “race/ethnicity” in the sentence “The SEER program records race as assigned by the North American Association of Central Cancer Registries.”

Answer: We have corrected it and marked it. (Page 3, 7, 9)

7. Results, page 10: the – declining – estimates for APC in whites, all as well as males and females, should be negative, i.e. -2.1, -1.8 and -2.4.

Answer: We have corrected it and marked it.

8. Caption for figure 1: add “incidence” to the word rate.

Answer: We have corrected it and marked it.

 

Revierwer #2:

Reviewer #2: (I) Summary

The authors of this manuscript explore recent trends in follicular lymphoma (FL) in Taiwan and United States (US) using cancer registry (Taiwan Cancer Registry and US SEER) data from 2008 to 2017 with the aim of elucidating incidence patterns in both populations. They provide recent data from both cancer registries on age-adjusted incidence rates, relative frequencies and annual percent changes (APC) of FL stratified by sex and race/ethnicity. Collected data show a steadily rising trend in FL incidence in Taiwan (+39% from 2008-17) as compared to declining incidences in US white population (-20% from 2008-17) and steady trend in Hispanic, black and Asian/Pacific Islander population. The authors discuss possible factors for changes in incidence (genetics, lifestyle, environment) and compared their newly gathered data on FL incidence to recent data from other Asian countries noting some similarities. They conclude that further etiological investigations in Asian countries are needed.

Answer: Thank you for your comment.

(II) Discussion of specific areas of improvement

1.) Abstract

- clear and concise, no comment

2.) Introduction

- no comment

3.) Materials and methods

- the US are ethnically quite diverse and how SEER handles ethnicity is explained in great detail, please add a short comment if ethnicity is an issue for the Taiwan Cancer Registry.

Answer: Individual data collected by Taiwan Cancer Registry doesn’t include patients’ ethnicity.

4.) Results

- 2nd paragraph, line 3: APCs and 95% CI are listed in Figures 1 and 2, while Table 1 provide only APCs, this should be corrected accordingly.

Answer: We have corrected it and marked it in Table 1.

-2nd paragraph, line 5: data of % change is provided for FL incidence in Taiwan (+39%), but no similar data provided for decrease in US white population, consider adding data.

Answer: We have provided it and marked it in 2nd paragraph, line 12: from 3·42 to 2·74 per 100,000 person-years between 2008 and 2017, representing a 20% decrease.

- S1 table: reference to study by Ko et al is 10 and not 8, please correct

Answer: We have corrected it and marked it for reference number in Supporting Information.

- S1 table: data for Korea12 and 15 shown with same color and symbol making it harder to read, consider correcting

Answer: We have corrected it and marked it: Korea_Lee, Korea_Kim.

- Table 1, whites, RF (%), APC: only variable with a joint point. Discuss with your statistician if an average APC could be calculated and added in the comment under the table or consider adding a comment why there are two number as opposed to all other APCs.

Answer: We have corrected it and marked it.

Page 17: In the whites, the relative frequency of FL among the incident NHL cases declined from 12.9% to 10.7%, the average APC was −1.8 (95% CI: −3.1% to −0.5%, p = 0.009).

5.) Discussion

- list possible limitations of this study and/or biases (for example: SEER data do not cover whole US population; incidence change in US white population cannot be generalized

Answer:

We have corrected it and marked it.

Page 21: The main limitation of this study is that SEER data does not cover whole US population, the incidence change in each racial population in US cannot be generalized. Another limitation of our study is that the FL data in Taiwan was retrieved from the TCR annual report, not Taiwan Cancer Registry Database. The number of FL cases by gender and age in the TCR annual report was defined by ICD-O-3 codes 9597/3, 9675/3, 9690/3, 9691/3, 9695/3, and 9698/3, that is different from the definition of FL in SEER. Although we could not know the number of cases in each ICD-O-3 codes, the ICD-O-3 code 9675/3 is not applicable since 2010. The cases with code 9597/3 were very rare in Taiwan, just one case was found in a medical center from January 1998 to December 2014 [41] and there were no case in other medical center between January 2001 and December 2010 in Taiwan [42], thus it would not affect the results in this study.

(III) Other comments

- very fluent reading, carefully edited text, no language issues.

Answer: Thanks for your comments.

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (23KB, docx)

Decision Letter 1

Amir Radfar

7 Jan 2022

PONE-D-21-21835R1Investigation of the incidence trend of follicular lymphoma from 2008 to 2017 in Taiwan and the United States using population-based dataPLOS ONE

Dear Dr. Su,

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.

Specifically,

  • Please make sure that the limitation section of your paper indicates" that despite the SEER database, the Taiwan Cancer registry doesn’t include patients’ ethnicity".

  • Please explain how the study handled missing data.

  • Please answer comments made by reviewer#3

Please submit your revised manuscript by Feb 21 2022 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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We look forward to receiving your revised manuscript.

Kind regards,

Amir Radfar, MD,MPH,MSc,DHSc

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: I Don't Know

Reviewer #3: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have adequately addressed all questions from the previous round of review posted by both reviewers. The manuscript has been improved in the Materials, Results and Discussion sections, tables and charts have been revised according to recommendations. At this point I have no further comments.

Reviewer #3: 1- Why the authors compared the incidence of FL in Taiwan and US? What is the rationale behind it?

2- It is highly recommended to provide the report based on the guidelines such as STROBE or the following: https://www.ncbi.nlm.nih.gov/books/NBK208602/.

The authors should provide some subheadings in the methods to cover the main following questions regarding registry data:

• Study purpose: Were the objectives/hypotheses predefined or post hoc?

• Patient population: Who was studied?

• Data quality: How were the data collected, reviewed, and verified?

• Data completeness: How were missing data handled?

• Data analysis: How were the analyses chosen and performed?

3- In the abstract the authors stated that “Our findings suggest that modifiable risk factors may be important determinants of the diverse trend of FL, especially in Taiwan.” This conclusion does not seem logical since the authors did not examine the role of modifiable risk factors in this study. Conclusions should be consistent with the findings of the study.

4- It is recommended to quantify the association of age, period, and cohort using age–period–cohort models.

5- Reporting incidence rate ratios (IRRs) for assess the cohort effect is recommended.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #2: No

Reviewer #3: No

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PLoS One. 2022 Mar 17;17(3):e0265543. doi: 10.1371/journal.pone.0265543.r004

Author response to Decision Letter 1

20 Jan 2022

Answer to Editor’s comments:

• Please make sure that the limitation section of your paper indicates" that despite the SEER database, the Taiwan Cancer registry doesn’t include patients’ ethnicity".

• Please explain how the study handled missing data.

• Please answer comments made by reviewer#3

Answer: Thank you for your reminder.

1. The TCR annual report does not include patients’ ethnicity have been confirmed.

2. The follicular lymphoma data in Taiwan and US available from the Taiwan Cancer Registry annual report of the Health Promotion Administration, Ministry of Health and Welfare, Taiwan and the US National Cancer Institute’s SEER 18 program, respectively. The cancer registry annual report based on the databased established by the Taiwan Cancer Registry which case completeness rates greater than 97%. The Taiwan Cancer Registry implemented rigorous quality control protocols to validate and verify cancer diagnoses, including submission of tissue pathology reports and random sampling of claims and diagnosis reports. It is considered a complete and accurate registry. The SEER program records race as assigned by the North American Association of Central Cancer Registries, which is only comprehensive source of population-based in the US and have a case completeness rate greater than 98%.

Answer to Reviewers’ comments:

Revierwer #2: The authors have adequately addressed all questions from the previous round of review posted by both reviewers. The manuscript has been improved in the Materials, Results and Discussion sections, tables and charts have been revised according to recommendations. At this point I have no further comments.

Answer: Thank you for your comments.

 

Revierwer #3:

1- Why the authors compared the incidence of FL in Taiwan and US? What is the rationale behind it?

Answer: We want to compare the trends for incidence rates of follicular lymphoma in Taiwan and other Asian ethnic groups in recent years, but we cannot obtain these data from Japan, South Korea and other Asian countries. Therefore, we compared the data for Taiwanese and Asian ethnic groups in US from SEER database, and also observed the trends for incidence rates of FL for other ethnic groups in US from SEER database.

2- It is highly recommended to provide the report based on the guidelines such as STROBE or the following: https://www.ncbi.nlm.nih.gov/books/NBK208602/.

The authors should provide some subheadings in the methods to cover the main following questions regarding registry data:

• Study purpose: Were the objectives/hypotheses predefined or post hoc?

• Patient population: Who was studied?

• Data quality: How were the data collected, reviewed, and verified?

• Data completeness: How were missing data handled?

• Data analysis: How were the analyses chosen and performed?

Answer: Thank you for your comments. We have provided it and marked it in red (Page 6-9).

3- In the abstract the authors stated that “Our findings suggest that modifiable risk factors may be important determinants of the diverse trend of FL, especially in Taiwan.” This conclusion does not seem logical since the authors did not examine the role of modifiable risk factors in this study. Conclusions should be consistent with the findings of the study.

Answer: Thank you for your comments. We have deleted this conclusion in the abstract.

4- It is recommended to quantify the association of age, period, and cohort using age–period–cohort models.

5- Reporting incidence rate ratios (IRRs) for assess the cohort effect is recommended.

Answer: Thank you for your comments. Since the number of FL cases in Taiwan were showed by age in 5-year age groups from the TCR annual report and the study period was from 2008 to 2017, the number of consecutive 5-year periods was just two, therefore, the age-period-cohort model was not applicable. We will use the age-period-cohort models in the future studies.

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (19.4KB, docx)

Decision Letter 2

Carla Pegoraro

4 Mar 2022

Investigation of the incidence trend of follicular lymphoma from 2008 to 2017 in Taiwan and the United States using population-based data

PONE-D-21-21835R2

Dear Dr. Su,

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,

Carla Pegoraro

Staff Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have addressed questions from the previous round of review. The manuscript has been adequately improved according to STROBE guidelines and presents data in a clear way. No further comments.

Reviewer #3: Dear editor

I reviewed the manuscript and all comments have been addressed adequately by authors.

regards

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

Acceptance letter

Carla Pegoraro

8 Mar 2022

PONE-D-21-21835R2

Investigation of the incidence trend of follicular lymphoma from 2008 to 2017 in Taiwan and the United States using population-based data

Dear Dr. Su:

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 plosone@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 Carla Pegoraro

Staff Editor

PLOS ONE

Associated Data

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    Supplementary Materials

    S1 File

    (DOCX)

    Click here for additional data file. (21.1KB, docx)
    S1 Fig. Trends in the age-standardized incidence rates of follicular lymphoma in Taiwan, Japan, and Korea.

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    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (23KB, docx)
    Attachment

    Submitted filename: Response to Reviewers.docx

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    Data Availability Statement

    All relevant data are within the manuscript and its Supporting Information files.

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