The association of Hashimoto’s thyroiditis with central lymph node metastasis in papillary thyroid cancer: a retrospective cross-sectional study

Introduction

Background

Papillary thyroid cancer (PTC) accounts for 90% of all thyroid malignancies (1). In recent years, the global incidence has exhibited a marked upward trend. This phenomenon can be attributed not only to advancements in diagnostic technologies and the widespread adoption of screening programs, but also to a growing number of environmental risk factors, such as ionizing radiation, pesticides, persistent organic pollutants, endocrine-disrupting chemicals, heavy metals, and polychlorinated biphenyls (2,3). PTC follows an indolent clinical course and is generally associated with a favorable prognosis. The overall survival (OS) rate for PTC is exceptionally high across all age groups, and the 10-, 15-, and 20 years OS rates are 97%, 95%, and 90%, respectively (4). Lymph node metastasis serves as an adverse prognostic factor. In accordance with the guidelines of the American Thyroid Association (ATA), for patients presenting with central lymph node involvement in the clinical context or within the neck region, central lymph node dissection ought to be carried out (5).

Currently, the treatment strategies for PTC tend to be conservative and minimally invasive. In this context, the controversy surrounding the lymph node dissection procedure has been intensifying steadily (6). According to the 2025 ATA, high-risk patients with PTC are recommended to undergo prophylactic central neck dissection (PCND) (5). However, this procedure carries potential risks, including recurrent laryngeal nerve injury (1.8–9%) and permanent hypoparathyroidism (2.6%), which can substantially impair patients’ quality of life (6). Therefore, preoperative assessment of lymph node metastasis plays a crucial role in determining the extent of surgery and selecting an appropriate strategy for central lymph node dissection. However, recent studies have shown that the effects of Hashimoto’s thyroiditis (HT) on lymph node metastasis in the central region vary.

Rationale and knowledge gap

HT is an autoimmune thyroid disorder characterized by clinical symptoms, presence of antithyroid antibodies, and distinct histological features. Serum anti-thyroid peroxidase (TPO) antibodies are present in approximately 95% of patients (7). Histologically, HT is characterized by diffuse lymphocytic infiltration involving the majority of the thyroid parenchyma, formation of lymphoid follicles with prominent germinal centers, and Hurthle cell changes (eosinophilic metaplasia) in the follicular epithelium (8). Numerous studies have demonstrated that patients with HT have a significantly higher risk of developing PTC than those without HT (9,10). This may be related to the chronic inflammatory microenvironment, elevated thyroid-stimulating hormone (TSH) levels, and molecular mutations, such as Rearranged during Transfection (RET) gene rearrangement (11). And some studies found that HT could be associated with a lower risk of CLNM (11,12). However, some studies have indicated that the protective effects of HT against CLNM are limited. Zeng et al. reported that HT is associated with a high risk of CLNM (13). Zhou et al. proposed that HT only has a weak inverse association on CLNM in N1a (reducing the risk by 16.4%), whereas in N1b, the risk increased by 1.336 times (14). A meta-analysis by Hafez et al. concluded that HT was not an independent predictor of large-volume CLNM (15). Other studies have found that the lymph node metastasis rate of PTC combined with HT is increased (15-17). These differences of these conclusions have hindered the further optimization and development of current clinical work.

The reasons for these conflicting findings are likely multifactorial. The main possibilities are as follows. First, diagnostic criteria for HT vary considerably across studies. Some studies define HT solely by seropositivity for anti-TPO antibodies, while others require strict histological confirmation (e.g., dense lymphocytic infiltration, germinal center formation, and Hurthle cell change). This heterogeneity may directly influence the reported association between HT and CLNM. Second, the extent of central neck dissection (CND) is not standardized across institutions; some surgeons perform routine prophylactic CND, whereas others adopt a selective approach. Variations in surgical radicality can significantly alter the detected CLNM rate, potentially masking or exaggerating the true effect of HT. Third, many previous studies inadequately controlled for key confounders such as age, sex, tumor size, multifocality, and preoperative thyroid function, leading to residual confounding.

Clinical value and study positioning

In the context of the trend towards minimally invasive surgery, extensive lymph node dissection in the neck is becoming increasingly controversial, because it carries well-documented risks, including permanent hypoparathyroidism (up to 2.6%) and recurrent laryngeal nerve injury (1.8–9%), which substantially impair patients’ quality of life (6). Therefore, identifying factors that can predict a low risk of CLNM is of paramount clinical importance to safely omit unnecessary PCND. If HT indeed exerts a protective effect against CLNM, then PTC patients with coexisting HT, especially those with other low-risk features, might be candidates for a more conservative surgical approach. This study is explicitly framed to provide evidence-based guidance for personalized surgical stratification: to determine whether the presence of HT can serve as a criterion for safely avoiding PCND, thereby balancing oncological radicality with postoperative quality of life.

Objective

To better study the association between HT and CLNM, we employed multivariable logistic regression on the full cohort, with propensity score matching (PSM) and weighting methods as sensitivity analyses, along with subgroup analyses to investigate the relationship between HT and CLNM in patients with PTC. This study aimed to offer evidence-based recommendations regarding the necessity of CLN dissection during PTC surgery. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0101/rc).

Methods

Study design

This retrospective cross-sectional study aimed to investigate the association between HT and CLNM in patients with PTC. Based on the complete data accessibility of the Second People’s Hospital of Liaocheng’s electronic medical record (EMR) system, we consecutively retrospectively collected clinical and pathological data from 1,157 patients aged 16–84 years with PTC who underwent their first thyroidectomy and lymph node dissection at the Second People’s Hospital of Liaocheng between January 1, 2015 and December 31, 2024. No specific convenience sampling method was applied; all eligible patients during this period were included. Data collection was completed from January 2025 to August 2025. This study was a pathological data analysis without clinical follow-up. Among these patients, 27 were excluded because of a history of malignant tumors in other organ systems, and an additional seven were excluded because they concurrently had other types of malignant thyroid neoplasms. Consequently, 1,123 patients with complete clinical data were included in the final analyses. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of the Second People’s Hospital of Liaocheng (approval No. 202508), and individual informed consent was obtained from all subjects and their legal guardians involved in the study. Demographic and clinical data, including age, sex, presence of bilateral lesions, extracapsular extension, tumor diameter (cm), multifocality, coexisting nodular goiter, adenoma, preoperative thyroid hormone levels, and a history of HT, were systematically collected from the EMR system and the pathology report system of hospital. HT was established based on the presence of diffuse lymphocytic infiltration, germinal center formation, and Hurthle cell change, as independently confirmed by two board-certified pathologists. According to the ATA guidelines, the central neck compartment (Level VI) is defined anatomically as the region bounded superiorly by the hyoid bone, inferiorly by the innominate artery, and laterally by the carotid arteries, specifically including the prelaryngeal, pretracheal, and bilateral paratracheal lymph nodes (18). CLNM was strictly defined as histologically metastatic involvement of at least one lymph node within this defined Level VI region during surgical dissection. The number of CLN that were dissected, the presence or absence of metastasis, and the final count of CLNM were recorded. The CLNM ratio was defined as the proportion of CLNM relative to the total number of CLNs dissected.

Covariates

Based on a comprehensive literature review and clinical expertise, the following covariates were incorporated into the study: sex, age, extrathyroidal extension (ETE), bilateral lesions, tumor diameter, multifocality, nodular goiter, follicular adenoma, and thyroid function parameters before surgery, including TSH, free triiodothyronine (FT3), and free thyroxine (FT4). ETE is defined as the infiltration of cancer cells through the thyroid capsule into the adjacent tissues and structures. Bilateral lesions revealed the presence of tumor foci in both left and right lobes of the thyroid gland. Multifocality denotes the existence of two or more distinct lesions, irrespective of whether they are confined to a single lobe or are distributed across both lobes. Adenomas included follicular adenomas, eosinophilic adenomas, and adenomatous nodules. All pathological assessments were conducted independently by two board-certified pathologists, and the final diagnoses were established based on consensus review. The determination of thyroid function (such as TSH, FT3, and FT4) was conducted using a single, consistently calibrated fully automatic electrochemiluminescence analyzer (Cobas e601, Roche Diagnostics) throughout the entire study period [2015–2024]. To ensure inter-assay consistency, quarterly internal quality controls were performed, and the laboratory participated in national external quality assessment schemes for thyroid hormones annually.

Statistical analysis

Progressive descriptive analyses were performed on all patients using R (version 4.4.3) and Free Statistics software (version 2.2.0). In the descriptive analysis, categorical variables (sex, bilateral lesions, extracapsular, multifocality, nodular goiter, adenoma, and CLNM) were presented as numbers with proportions (%); continuous variables were reported as means with standard deviation (SD), such as age, FT3, and FT4, or medians with interquartile range (IQR), such as TSH, tumor diameter, number of CLN and CLNM dissected, and ratio of CLNM, depending on their distribution. The normal distribution is judged by the Shapiro-Wilk test (P>0.05 is considered to conform to the normal distribution). The Chi-squared test was used for categorical variables, one-way analysis of variance (ANOVA) was employed for normally distributed variables, and the Kruskal-Wallis test was used for variables with skewed distributions. To handle missing data (18% of patients had at least one missing thyroid function value), consecutively was performed using Free Statistics software. The imputation model included all complete covariates as predictors and generated five independent imputed datasets. One of these datasets was used for all subsequent analyses, including descriptive statistics, PSM, multivariable regression, and subgroup analyses. To assess the robustness of our findings to missing data handling, we also performed a complete case analysis as a sensitivity analysis (excluding the 202 patients with any missing data), and the results were consistent with the primary analysis. Additionally, we conducted subgroup analyses in which quantitative variables, including age groups and tumor diameter categories, were categorized based on the age-related risk stratification for differentiated thyroid cancer and the commonly used clinical T-stag thresholds from the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system. Age was dichotomized as <55 and ≥55 years, while tumor diameter was divided into ≤2, >2 cm and ≤4, and >4 cm groups.

To minimize allocation bias and confounding factors, multivariate logistic regression with PSM was employed with CLNM as the independent variable. A 1:1 nearest neighbor matching algorithm with a caliper width of 0.2 was used. All covariates were included in propensity score analysis. The standardized mean difference (SMD) was used to assess the degree of PSM, with a threshold of less than 0.1 considered acceptable. Using the estimated propensity scores as weights, the inverse probability of treatment weighting (IPTW) and standardized mortality ratio weighting (SMRW) were used to generate a weighted cohort (19,20). The area under the receiver operating characteristic (ROC) curve was computed to assess the balance of covariates, and the corresponding area under the curve (AUC) value was documented. Subgroup analyses were conducted based on relevant covariates to explore potential effect modifications. Interaction across subgroups was tested using the likelihood ratio test. Significance levels were interpreted as two-sided. P<0.05 was considered statistically significant. This study continuously enrolled patients with complete clinical data between January 1, 2015 and December 31, 2024. To address missing data, multiple imputation was applied to individual variables with incomplete observations.

Results

Population characteristics

A total of 1,157 patients aged 16–84 years who underwent their first thyroidectomy were included in this study. After excluding 27 patients with a history of other systemic malignancies and seven patients with other concurrent thyroid malignancies, a final cohort of 1,123 patients was retained for the cross-sectional analysis. Among these, 243 (21.6%) had HT. Following PSM, 239 well-matched pairs were identified (Figure 1). Among 243 patients with HT, 227 (93.4%) were women, whereas among 880 patients without HT, 656 (74.5%) were women. The prevalence of nodular goiters in the two groups was 385 (43.8%) and 55 (22.6%), respectively. The median TSH levels were 1.8 (IQR, 1.2, 2.6) µIU/mL and 2.1 (IQR, 1.4, 3.3) µIU/mL, respectively. After matching, both groups demonstrated excellent balance. Specifically, the number of females in the non-HT and HT groups was 221 (92.5%) and 223 (93.3%), respectively, while the mean ages were 47.2±12.2 years and 47.8±11.5 years, respectively. All variables were complete except for thyroid function indicators (TSH, FT3, FT4), with 202 patients (18.0%) missing at least one value. Additional demographic and clinical characteristics of all participants and the matched cohort are summarized in Table 1.

Figure 1 Flowchart of arrangement. A total of 1,157 patients who underwent their first thyroidectomy were included in this study. After excluding 27 patients with a history of other systemic malignancies and 7 patients with other concurrent thyroid malignancies, a final cohort of 1,123 patients was retained for the cross-sectional analysis. Among these, 243 (21.6%) had HT. Following PSM, 239 well-matched pairs were identified. HT, Hashimoto’s thyroiditis; PSM, propensity score matching; PTC, papillary thyroid cancer.

Primary analysis: multivariable logistic regression in the full cohort

Multivariable logistic regression adjusting for all 13 covariates demonstrated that HT was independently associated with a significantly reduced risk of CLNM [adjusted odds ratio (OR) = 0.68; 95% confidence interval (CI): 0.49–0.94; P=0.02]. Unadjusted analysis yielded an OR of 0.62 (95% CI: 0.47–0.83; P=0.001).

In the full cohort, the crude incidence of CLNM was significantly lower in the HT group than in the non-HT group (43.6% vs. 55.5%; P=0.001). Similarly, both the number and ratio of CLNM were significantly lower in the HT group than in the non-HT group [ 0.0 (0.0, 2.0) vs. 1.0 (0.0, 3.0); rate: 0.0 (0.0, 0.3) vs. 0.2 (0.0, 0.7), respectively; P<0.001]. Furthermore, the total number of CLN was significantly higher in the HT group (P<0.001). In the multivariable logistic regression model, the area under the ROC curve for predicting CLNM was 71.7% (Figure 2A).

Figure 2 Comprehensive evaluation of the effects of propensity score matching. (A) The ROC curve shows that the predictive ability of the propensity score model for treatment allocation is moderate (AUC =71.7%). At a cutoff value of 0.3, the sensitivity is 69.0% and the specificity is 66.3%, suggesting that the model has an acceptable discriminatory ability. (B) This stacked dot plot presents the SMD of 11 covariates including gender, nodular goiter, TSH, tumor diameter, age, extrathyroidal invasion, bilateral lesions, FT4, FT3, multifocality, and adenoma in the original cohort (unmatched) and five propensity score adjustment schemes (matched, weighted-IPTW, weighted-SMRW, weighted-PA, weighted-overlap). The horizontal axis represents the absolute value of SMD, and the vertical axis lists each covariate. Generally, an |SMD| <0.1 indicates good balance between groups. It can be seen that in the original cohort, the SMD of most covariates is greater than 0.1, suggesting significant baseline differences; however, after propensity score matching or weighting, the SMD of all covariates drops below 0.1, indicating that each adjustment scheme successfully achieves balance of covariates between groups. (C) Both prior to and following PSM, HT was inversely associated with CLNM (OR =0.62, 95% CI: 0.47–0.83, P=0.001; OR =0.67, 95% CI: 0.47–0.96, P=0.02, respectively). This consistency was maintained even after adjusting for all covariates in the model (OR =0.68, 95% CI: 0.49–0.94, P=0.02). Likewise, weighted analyses conducted using IPTW (OR =0.74, 95% CI: 0.56–0.98) and SMRW (OR =0.7, 95% CI: 0.53–0.94) also produced congruent findings. (A) ROC curve for CLNM. (B) SMD before and after propensity-score adjustment. (C) The associations between HT and CLNM using different statistical models. AUC, area under the curve; CI, confidence interval; CLNM, central lymph node metastasis; FT3, free triiodothyronine; FT4, free thyroxine; HT, Hashimoto’s thyroiditis; IPTW, inverse probability of treatment weighting; OR, odds ratio; PA, propensity score adjusted; PSM, propensity score matching; ROC, receiver operating characteristic curve; SMD, standardized mean differences; SMRW, standardized mortality ratio weighting; TSH, thyroid-stimulating hormone.

Sensitivity analyses: PSM and weighting

To assess the robustness of the primary finding, we performed multiple sensitivity analyses. First, after 1:1 PSM (239 well-matched pairs), the risk of CLNM remained significantly lower in the HT group (43.5% vs. 53.6%, P=0.03). The number of metastatic CLNs, total dissected CLNs, and CLNM rates in the HT group were consistent with those observed prior to PSM (Table 2). The covariate balance before and after PSM is shown in Figure 2B. Second, IPTW confirmed the inverse association (OR =0.74; 95% CI: 0.56–0.98; P=0.04). Third, SMRW produced a consistent result (OR =0.70; 95% CI: 0.53–0.94; P=0.02). All sensitivity analyses supported the primary finding that HT is associated with a reduced risk of CLNM (Figure 2C). Fourth, to assess the impact of missing data handling, we repeated the multivariable logistic regression using complete case analysis (excluding 202 patients with missing thyroid function values). The association between HT and CLNM remained significant (adjusted OR =0.67; 95% CI: 0.48–0.94; P=0.02), consistent with the primary analysis using multiple imputation.

Subgroup analysis

Subgroup analyses revealed that HT was associated with a reduced risk of CLNM across most subgroups. This association was particularly pronounced in the female sub-group (OR =0.67; 95% CI: 0.46–0.98), individuals aged under 55 years (OR =0.58; 95% CI: 0.38–0.89), patients with multifocal tumors (OR =0.54; 95% CI: 0.31–0.93), and those without concurrent adenoma (OR =0.66; 95% CI: 0.46–0.96). Notably, no significant interaction effects were observed among the subgroups (Figure 3).

Figure 3 Subgroup analysis evaluating the relationship between HT and CLNM in patients with PTC. Subgroup analyses revealed that HT was associated with a reduced risk of CLNM across all subgroups. This association was particularly pronounced in the female subgroup (OR =0.67, 95% CI: 0.46–0.98), individuals aged under 55 years (OR =0.58, 95% CI: 0.38–0.89), patients with multifocal tumors (OR =0.54, 95% CI: 0.31–0.93), and those without concurrent adenoma (OR =0.66, 95% CI: 0.46–0.96). Notably, no significant interaction effects were observed among the subgroups. CI, confidence interval; CLNM, central lymph node metastasis; ETE, extrathyroidal extension; HT, Hashimoto’s thyroiditis; OR, odds ratio; PTC, papillary thyroid cancer.

Discussion

Key findings

In this cross-sectional study of patients with PTC, using multivariable regression and sensitivity analyses including PSM, we found that HT was associated with a significantly reduced risk of CLNM. In addition, HT not only markedly decreased the number of CLNM but also increased the total number of lymph nodes, thereby reducing the ratio of CLNM. Subgroup analysis further revealed that the inverse association of HT was more pronounced in female patients, those aged <55 years, patients with multifocal tumors, and individuals without concurrent adenoma. The findings indicate that the inverse association between HT and CLNM is particularly evident in specific patient subgroups with HT, especially in women and those younger than 55 years.

Comparison with similar research

This study confirmed, after further verification by PSM, that HT was associated with a significantly reduced risk of CLNM in patients with PTC, which aligned with the reported observed inverse association (13,14,18). Consistently, a recent large-scale retrospective study focusing specifically on papillary thyroid microcarcinoma (PTMC) by Huang et al. also demonstrated a negative association between HT and lymph node metastasis. After PSM (2,324 matched pairs), HT was associated with significantly lower risks of CLNM, as well as fewer positive lymph nodes (21). Regarding the situations of PTC and HT, more detailed and in-depth studies have been conducted. Zhou demonstrated that this conclusion applies exclusively to patients with N1a stage tumors (14). Furthermore, Hafez did not provide evidence to support HT as a predictive factor for large-volume CLNM (15). In comparison with previous studies, this study simultaneously accounted for 13 high-risk factors for CLNM (including thyroid function parameters such as TSH/FT3/FT4, adenoma, and multifocality) and validated the robustness of the results using two weighting methods (IPTW and SMRW). Specifically, subgroup analysis indicated that the inverse association of HT was more pronounced in patients without adenomas (OR =0.66), suggesting that adenomas may serve as a critical confounding variable that obscures the true effect of HT.

Explanations of findings

The observed inverse association between HT and CLNM in patients with PTC is likely underpinned by a complex interplay of immunological, molecular genetic, and endocrine mechanisms. Recent experimental and translational studies, including single‑cell transcriptomic analyses, have substantially advanced our understanding of how pre‑existing thyroiditis may modulate PTC behavior.

First, HT is characterized by extensive lymphocytic infiltration, particularly by CD8 + cytotoxic T lymphocytes and plasma cells (22). Experimental evidence from the NOD.H2^h4 mouse models has demonstrated that pre-existing thyroiditis exerts a beneficial effect on PTC growth and progression through a distinctive expansion of effector memory CD8⁺ T cells (23,24). This enhances local immunosurveillance may effectively inhibit tumor cell migration and their ability of lymphatic vessel infiltration, thereby restricting early CLNM. Furthermore, a recent single-cell RNA sequencing study by Ma et al. provided high‑resolution insights into the HT‑PTC tumor microenvironment using 140,456 cells from 11 patients. The authors identified that HT patients have significantly higher proportions of specific immune cell subsets, including CD4⁺ Tn Tregs, CD8⁺ Tex Teffs, intermediate B cells, and conventional dendritic cells (cDCs), indicating better activation of the immune system in HT patients. Notably, the high proportion of CD4⁺ Tn Tregs helps prevent excessive immune activation to maintain homeostasis, while CD8⁺ Tex Teffs effectively mobilize the immune system to kill PTC cells. In addition, they also proved HT-specific cell populations facilitate intricate immune-stromal communication through the MIF-(CD74 + CXCR4) signaling axis, emphasizing the role of immune regulation in modulating tumor progression (25).

Second, BRAF mutations have been demonstrated to contribute to a more aggressive clinical course in patients with PTC (26,27). Previous studies have shown that patients with PTC and concomitant HT exhibit a lower prevalence of BRAF mutations (11), and tumors negative for BRAF mutations have lower invasiveness in the context of HT (28). Interestingly, Ma et al. further validated that in The Cancer Genome Atlas-Thyroid Carcinoma (TCGA-THCA) cohort, molecular subtyping based on HT-associated specific cell populations (HASCs) revealed two distinct clusters with different mutation patterns: cluster 1 (HT-like) showed higher tumor mutation burden and better drug sensitivity to chemotherapeutic agents such as sunitinib, paclitaxel, and vinblastine, while cluster 2 showed mutations in NRAS and HRAS. It suggests that the immune microenvironment associated with HT may inhibit the development or progression of BRAF mutations (25,29).

Third, although HT is often accompanied by elevated TSH levels, some subsets of HASCs, marked by malignant thyroid epithelial cells 3 (mTE3), non-malignant thyroid epithelial cells 0 (nTE0), and non-malignant thyroid epithelial cells 2 (nTE2) cells enriched in thyroid hormone pathways, may exert their biological functions through the thyroid hormone metabolic pathway, leading to increased production of thyroid hormones and subsequent suppression of TSH secretion, thereby contributing to the establishment of a TSH-suppressive microenvironment (17,25,30).

Taken together, these mechanistic hypotheses—enhanced immune surveillance (via effector memory CD8⁺ T cells, CD4⁺ Tn Tregs, CD8⁺ Tex Teffs, intermediate B cells, and cDCs), TSH suppression (via mTE3/nTE0/nTE2 thyroid cell clusters and MIF signaling), and reduced prevalence of BRAF mutations—are not mutually exclusive. Rather, they may operate synergistically to create a tumor microenvironment that is less permissive for lymphatic dissemination. Future studies integrating multi‑omics approaches (e.g., single‑cell transcriptomics coupled with targeted mutational profiling) are warranted to further elucidate the causal relationships underlying these associations.

Strengths and limitations

This study has several key strengths, including a large sample size that ensured adequate statistical power, rigorous control of 13 potential confounders through PSM, and validation of the robustness of findings via multiple methods (multivariable regression, IPTW, SMRW) and sensitivity analyses. In addition, multiple imputation was used to address missing data and minimize selection bias, while subgroup analyses provided valuable insights to support individualized clinical decision-making.

Despite the consistency of our findings across multiple analyses, this study has several limitations. First, the study design was retrospective, which may have introduced selection bias and limited the causal inference of the observed associations (31). However, further prospective studies are required to validate our findings. Second, although we accounted for multiple potential confounding factors in our analysis, residual confounding factors may still exist. For example, the presence of other autoimmune diseases and use of thyroid hormone replacement therapy were not considered in our analysis. Third, the study population was limited to a single center in China, which may limit the generalizability of our results to other populations. Additionally, the relatively sample size of HT was relatively small and the study period was relatively long, which may have introduced variability in surgical techniques and pathological assessments over time.

Implications and actions needed

The study provides evidence that HT is associated with a reduced risk of CLNM in patients with PTC, particularly in specific subgroups. This finding suggests that HT may play an important role in the metastatic process of PTC and highlights the need for further investigation of the underlying mechanisms. Future studies should focus on elucidating the immune and molecular interactions between HT and PTC, as well as exploring the potential clinical implications of these findings for the management of patients with PTC and HT.

Conclusions

This study, using multivariable logistic regression on the full cohort and validated by PSM and weighting methods, confirms that coexisting HT is significantly associated with a lower risk of CLNM in patients with PTC (adjusted OR =0.68; 95% CI: 0.49–0.94; P=0.02), with a more pronounced inverse association observed in subgroups such as females and patients aged <55 years. This finding was consistently supported by sensitivity analyses. This conclusion, sustained after controlling for 13 potential confounders, provides strong evidence to address ongoing clinical debate. Consequently, for PTC patients with HT, surgical decision-making should involve a more cautious evaluation of the necessity for prophylactic CND, aiming to better balance oncological radicality and patient quality of life.

Acknowledgments

We thank the Second People’s Hospital of Liaocheng for providing resources, laboratory facilities, data access, and administrative assistance.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0101/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0101/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0101/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0101/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of the Second People’s Hospital of Liaocheng (approval No. 202508), and individual informed consent was obtained from all subjects and their legal guardians involved in the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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