- Research
- Open access
- Published:
Hypothyroidism following immunotherapy predicts more postoperative complication in oral squamous cell carcinoma
BMC Cancer volume 25, Article number: 643 (2025)
Abstract
Objective
To evaluate the impact of hypothyroidism that develops following immunotherapy on surgical outcomes in patients diagnosed with oral cancer.
Methods
Patients with surgically treated oral cancer following neoadjuvant immunochemotherapy were retrospectively enrolled. Impact of hypothyroidism on postoperative complication were analyzed.
Results
In total, 303 patients were enrolled. In comparison to patients with normal thyroid function, patients with subclinical or overt hypothyroidism did not exhibit a significantly increased risk of surgical site infection, but both conditions were associated with a higher risk of fistula formation and wound debridement. The cohort suffering from subclinical hypothyroidism exhibited odds ratios (ORs) of 1.88 [95% confidence interval (CI): 1.12–5.47] for fistula development and 1.95 [95% CI: 1.27–6.98] for wound debridement. Patients with overt hypothyroidism had a 2.03-fold higher risk of fistula formation (95% CI: 1.35–6.24) and a 2.17-fold higher risk of wound debridement (95% CI: 1.20–7.53). The rate of wound debridement escalated to 40.0% when both hypothyroidism and diabetes were present simultaneously; in contrast, it diminished to 20.0% in cases of isolated hypothyroidism, 12.1% in individuals with diabetes alone, and a mere 5.2% in patients devoid of both conditions. The incidence of fistula formation was most pronounced in patients with coexisting diabetes and hypothyroidism, followed closely by 6.7% in those with solely hypothyroidism. The occurrence of fistulas was remarkably rare among patients with only diabetes or those lacking both factors.
Conclusions
Hypothyroidism induced by neoadjuvant immunotherapy exerts a considerable negative impact on the formation of fistulas and wound debridement in patients with locally advanced oral cancer, an effect that may be exacerbated by the presence of diabetes.
Introduction
Oral squamous cell carcinoma (SCC) is the most prevalent malignancy among all head and neck cancers, with half or more of these cases presenting in a locally advanced stage at the commencement of therapy, primarily due to lymph node metastasis [1]. Traditionally, complete excision has remained the primary treatment modality, often followed by adjuvant radiotherapy or chemoradiation [2, 3].
While conventional neoadjuvant chemotherapy regimens that focus on platinum-based agents have not demonstrated a significant enhancement in survival rates for oral SCC [4], they have been associated with a notable increase in the likelihood of mandible preservation, approaching 50% [5]. As our comprehension of immune checkpoint pathways deepens, immunotherapy has emerged as a superior alternative to traditional chemoradiotherapy, contributing to extended overall survival in patients with recurrent or metastatic head and neck SCC [6, 7]. Consequently, immunotherapy has become the frontline treatment for such cases. The incorporation of immunotherapy into neoadjuvant protocols has garnered considerable interest, with a series of clinical trials showing that neoadjuvant immunotherapy, with or without the addition of chemotherapy, can achieve an impressive objective response rate that exceeds 95%. Furthermore, pathologic complete response rates of 30% or higher, along with major pathologic response rates nearing 70%, have been documented [8, 9].
However, the occurrence of immune-related adverse events (irAEs) demands significant attention, as conditions such as immune-related pneumonia can pose fatal risks to patients. Hypothyroidism emerges as the most frequently encountered adverse event, affecting up to approximately 70% of individuals undergoing immunotherapy [10]. It is well recognized that patients with hypothyroidism face an elevated incidence of postoperative fistula following salvage oropharyngectomy [11] and are more prone to flap compromise and the necessity for postoperative debridement in cases of osteoradionecrosis requiring free flap reconstruction [12], but prior radiotherapy may complicate the situation considerably. A recent extensive study reveals that hypothyroidism is associated with a 12.2% increase in the odds of readmission due to issues such as wound dehiscence, fistula formation, infection, and electrolyte imbalances [13]. Nonetheless, this study is significantly limited by its variability in surgical procedures.
Therefore, our objective was to evaluate the impact of hypothyroidism that develops following immunotherapy on surgical outcomes in patients diagnosed with oral SCC.
Patients and methods
Ethical approval
This study received approval from the Zhengzhou University Institutional Research Committee, and written informed consent for medical research was obtained from all patients prior to the initiation of treatment. All methodologies were executed in accordance with the relevant guidelines and regulations.
Study design
To fulfill our objective, a retrospective review of medical records of patients with surgically treated primary oral SCC between January 2020 and December 2024 at a tertiary hospital was conducted. The sole inclusion criterion was the administration of neoadjuvant immunochemotherapy, but patients with hypothyroidism confirmed prior to neoadjuvant therapy were excluded. Data concerning demographics, treatment, and pathology were meticulously extracted.
Study variables
Both albumin levels and thyroid function were assessed in all patients before, during, and after neoadjuvant therapy. Overt hypothyroidism is defined by a thyroid-stimulating hormone (TSH) concentration exceeding the normal range (0.27–4.2 mIU/L) alongside a free thyroxine (FT4) concentration falling below the laboratory reference range (12–22 pmol/L). Subclinical hypothyroidism is characterized by an elevated TSH concentration while FT4 levels remain within the reference range [14]. Body mass index (BMI) was calculated from the patient’s weight and height, with a normal range established at 18.5 to 23 for individuals of Asian descent [15]. The normal range for albumin levels was determined to be between 40 and 55 g/L. Perioperative blood glucose level maintained from 8.0 to 10.0 mmol/L for diabetes patients.
Free flap failure was defined as a free flap that succumbs to complete necrosis due to loss of perfusion. Free flap compromise was characterized as flaps displaying evidence of reduced or total loss of perfusion, originating from either arterial or venous sources, necessitating operative microvascular revision. Conversely, free flap salvage referred to a flap that, having experienced diminished or complete loss of perfusion, underwent a microvascular revision in which vascular flow was successfully reestablished.
The primary outcome variable assessed was the influence of hypothyroidism on surgical outcomes, which encompassed surgical site infection, free flap failure, free flap compromise, free flap salvage, total necrosis of pedicled flaps, partial necrosis of pedicled flaps, wound debridement, fistula development, and 30-day readmission.
Treatment program
For individuals suffering from subclinical hypothyroidism, supplementation with levothyroxine was not administered. However, patients with overt hypothyroidism typically received an initial dose of Levothyroxine ranging from 25 to 50 micrograms daily, which was subsequently tailored in accordance with the results of thyroid function tests. Moreover, the restoration of normal thyroid function prior to surgery was not an absolute prerequisite.
The treatment protocols comprised the administration of cisplatin at a dosage of 75 mg/m² on days 1 and 2, docetaxel at 75 mg/m² on days 1 and 8, and pembrolizumab or other PD-1 inhibitors at 200 mg on day 4 of each three-week cycle for two or three cycles. Surgical intervention was scheduled within one to four weeks following the completion of the six-week neoadjuvant regimen. Surgical strategies and resection margins were predefined based on baseline evaluations prior to neoadjuvant therapy and remained unchanged regardless of treatment response. Postoperative antibiotic therapy was routinely sustained for a minimum of five days.
Statistical analysis
A univariate analysis was executed employing chi-square and Fisher’s exact test for categorical variables. Significant variables in the univariate analyses were further analyzed in a multivariable logistic regression. Two-sided tests were carried out, with a p-value of less than 0.05 indicating statistical significance. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). All statistical analyses were conducted using R 3.4.4.
Results
Baseline data
In total, 303 patients were enrolled in the study, with a mean age of 55 ± 14 years. The cohort comprised 238 males (78.5%) and 65 females (21.5%). Among these individuals, 142 (46.9%) were identified as smokers and 88 (29.0%) as drinkers. Diabetes was present in 63 patients (20.8%). Low albumin levels were observed in 101 patients (33.3%). The BMI was categorized as low in 54 patients (17.8%), normal in 201 patients (66.3%), and high in 48 patients (15.8%). The cancer staging revealed 189 patients (62.4%) diagnosed with stage III and 114 patients (37.6%) with stage IV. Among the reconstructive procedures, free flaps were applied in 180 patients (59.4%), while pedicled flaps were used in 123 patients (40.6%). Hypothyroidism was diagnosed in 60 patients (19.8%), of whom 22 cases were classified as overt and the remainder as subclinical. In comparison with patients exhibiting normal thyroid function, individuals characterized by subclinical and overt hypothyroidism demonstrated a higher propensity for positivity of anti-Tg antibodies (p = 0.011) and anti-TPO antibodies (p < 0.001). (Supplementary Table 1)
A total of 32 patients experienced surgical site infections, yielding an incidence rate of 10.6%. Wound debridement was performed in 33 patients (10.9%), while fistulas developed in 12 patients (4.0%). Additionally, 15 patients (5.0%) underwent readmission within 30 days. Among those who received free flap reconstruction, 15 flaps encountered vascular crises, with 10 cases of venous compromise and 5 cases of arterial compromise, of which 9 were ultimately salvaged. In the cohort undergoing pedicled flap procedures, complete necrosis was observed in one patient, with partial necrosis documented in 19 patients.
Univariate analysis
Tables 1, 2, 3 and 4 illustrate the univariate analysis concerning the influence of hypothyroidism, diabetes, albumin, and BMI on surgical outcomes, and the impact of additional factors on these complications was detailed in Supplementary Tables 2–5. Those significant factors were further analyzed in a multivariable logistic regression.
Neither albumin levels nor BMI demonstrated any significant effect on the occurrence of surgical complications (all p > 0.05). Conversely, hypothyroidism exhibited a substantial association with the formation of fistulas (p = 0.001) and the necessity for wound debridement (p < 0.001), yet it did not significantly affect other adverse outcomes, but exhibited a tendency to influence the incidence of surgical site infections (p = 0.084). Moreover, patients with diabetes were more prone to experience surgical site infections (p = 0.014), the need for wound debridement (p < 0.001), and the development of fistulas (p = 0.021), while showing no correlation with other events (all p > 0.05).
Multivariable analysis
A multivariable analysis of independent predictors was conducted regarding surgical site infections, fistula formation, and wound debridement (Table 5, Supplementary Table 6). In comparison to patients with normal thyroid function, those afflicted with subclinical or overt hypothyroidism did not evince an augmented risk of surgical site infection. Nonetheless, the cohort with subclinical hypothyroidism exhibited ORs of 1.88 [95% CI: 1.12–5.47] for the formation of fistula and 1.95 [95% CI: 1.27–6.98] for wound debridement, whereas patients with overt hypothyroidism had a 2.03-fold higher risk of fistula formation (95% CI: 1.35–6.24) and a 2.17-fold higher risk of wound debridement (95% CI: 1.20–7.53). When compared to patients without diabetes, those characterized by diabetes demonstrated ORs of 2.92 (95% CI: 1.57–7.44) for surgical site infections, 3.14 (95% CI: 1.53–8.56) for fistula development, and 2.69 (95% CI: 1.27–8.99) for wound debridement. However, smoking status did not impinge upon the three outcome variables.
Subgroup analysis
Both hypothyroidism and diabetes exhibited independent effects on fistula formation and wound debridement, prompting a subgroup analysis of the interplay between these two factors, as illustrated in Fig. 1. The rate of wound debridement escalated to 40.0% when both hypothyroidism and diabetes were present simultaneously; in contrast, it diminished to 20.0% in cases of isolated hypothyroidism, 12.1% in individuals with diabetes alone, and a mere 5.2% in patients devoid of both conditions. The incidence of fistula formation was most pronounced in patients with coexisting diabetes and hypothyroidism, followed closely by 6.7% in those with solely hypothyroidism. The occurrence of fistulas was remarkably rare among patients with only diabetes or those lacking both factors.
Discussion
Our most significant finding was that, in the context of locally advanced oral SCC, hypothyroidism that arises during neoadjuvant immunochemotherapy is markedly associated with both wound debridement and fistula formation, with the adverse effects not being contingent upon the specific type of hypothyroidism. Moreover, the detrimental influence of hypothyroidism appears to be exacerbated by the presence of diabetes. This study represents the first of its kind to examine the implications of hypothyroidism following neoadjuvant immunochemotherapy in oral SCC and reveals the necessity for heightened vigilance to prevent fistula formation and wound debridement.
Hypothyroidism can sometimes manifest asymptomatically with minimal clinical ramifications; however, when left untreated, it poses a significant risk for morbidity and, ultimately, mortality. A substantial body of literature has examined the impact of hypothyroidism on surgical outcomes. Ang et al. [16] conducted a review encompassing seven studies with a total of 1,132 patients with hypothyroidism and 11,753 euthyroid individuals undergoing percutaneous coronary intervention. Although both cohorts exhibited no differences in the incidence of myocardial infarction, major adverse cardiovascular and cerebrovascular events, or heart failure, the hypothyroid group displayed a significantly elevated risk of cardiovascular mortality, all-cause mortality, and repeat revascularization. Rosko et al. [17] sought to delineate the effects of hypothyroidism on postoperative wound healing in 182 patients undergoing salvage laryngectomy, revealing a fistula rate of 47% among hypothyroid patients compared to 23% in their euthyroid counterparts. Multivariate analysis indicated that patients experiencing hypothyroidism in the postoperative period had a 3.6-fold increased risk of fistula formation. Moreover, those with hypothyroidism faced an 11.4-fold greater likelihood of requiring reoperation (24.4% vs. 5.4%) than their euthyroid peers, with the risk for both fistula and reoperation escalating in accordance with rising TSH levels. Specifically, each doubling of TSH corresponded to an approximate 12.5% incremental increase in the absolute risk of fistula and a 10% increase in the absolute risk of reoperation. In the context of total hip arthroplasty [18], patients with hypothyroidism exhibited a higher prevalence of postoperative acute anemia and incurred greater mean hospital costs compared to the non-hypothyroid group. Li et al. [19] reported that, although no significant differences were noted in terms of mortality, organ system complications, wound dehiscence, or other postoperative metrics between patients with and without hypothyroidism in breast reconstruction, the hypothyroid cohort did possess a heightened risk for hemorrhage and hematoma. Collectively, these studies underscore that hypothyroidism is a predictor of increased postoperative adverse events. However, it is essential to acknowledge that in the studies referenced, hypothyroidism was often attributed to chronic autoimmune thyroiditis or prior radiotherapy. In the former scenario, the immune system erroneously targets the thyroid gland, precipitating chronic inflammation and cellular degradation; concurrently, an influx of lymphocytes infiltrates the thyroid, progressively undermining the integrity of the thyroid tissue [20]. In the latter case, radiotherapy induces the destruction of thyroid cells via ionizing radiation, resulting in their dysfunction or annihilation. Moreover, radiotherapy can impair the blood vessels and adjacent tissues of the thyroid gland, compromising blood circulation and further exacerbating the impairment of thyroid functionality [21]. Notably, hypothyroidism may also arise as a side effect of immunotherapy, a prominent focus in cancer treatment. Consequently, the potential for a similar detrimental influence resulting from immunotherapy-induced hypothyroidism remains ambiguous.
In this study, we incorporated several well-established indicators for assessing postoperative complications and discovered that hypothyroidism is a predictor of an increased risk of fistula formation and wound debridement, with comparable probabilities observed between subclinical and overt forms of the condition. This finding is significant for several reasons. First, immunotherapy has emerged as an essential component in the initial management of locally advanced oral SCC [22]. While current literature has predominantly examined the incidence and patterns of adverse events, with conclusions suggesting that neoadjuvant immunotherapy does not delay surgical schedules [23], our study provides the inaugural evidence of the adverse effects of hypothyroidism on wound healing, thus offering valuable insights for clinical management in these scenarios. Secondly, overt hypothyroidism tended to introduce additional complications; typically, higher TSH levels are associated with greater difficulties in healing compared to lower levels, and overt forms of hypothyroidism are linked to an increased risk of complications [24]. This discrepancy may be elucidated by the fact that, unlike previous studies, thyroid function was rigorously monitored during immunotherapy. Even when free T4 levels did not return to the normal range, the timely administration of levothyroxine mitigated the detrimental effects commonly associated with overt hypothyroidism. Thirdly, subclinical hypothyroidism was similarly correlated with an increased incidence of surgical complications. Potential explanations may involve disruptions to the immune response, impairments in angiogenesis, or a deceleration of metabolism following immunotherapy [25].
In addition to hypothyroidism, factors such as albumin levels, smoking, diabetes, and BMI also significantly influence wound healing. In a cohort of 415 patients undergoing free tissue transfer [26], type 2 diabetes was identified as an independent risk factor for increased infectious complications, a finding that aligns with our analysis. Low albumin levels were correlated with the need for a second flap procedure [12], while a higher prevalence of abdominal aortic aneurysm among obese patients has been documented [27]; smoking resulted in a 2.49 times higher overall complication rate [28]. However, these results appear to contradict our findings. Potential explanations might include the relatively mild severity of hypoproteinemia in our study, as well as the fact that the most significant negative impact of BMI was attributed to prolonged operation times due to intraoperative exposure difficulties. Another noteworthy finding from our study was the interaction between hypothyroidism and diabetes; the incidence of adverse events, particularly wound debridement, was significantly heightened in the presence of both conditions. This carries substantial clinical implications, given the widespread prevalence of diabetes and the critical need for meticulous perioperative management in affected patients.
We must acknowledge several limitations in the current study: firstly, there is an inherent bias associated with retrospective research; secondly, our sample size may be inadequate, potentially reducing the statistical power of our findings confirmed by Bootstrap analysis, a substantial cohort from a multicenter investigation was imperative; lastly, our analysis was confined to a single institution, highlighting the necessity for external validation.
In conclusion, hypothyroidism induced by neoadjuvant immunotherapy exerts a considerable negative impact on the formation of fistulas and wound debridement in patients with locally advanced oral cancer, an effect that may be exacerbated by the presence of diabetes.
Data availability
All data generated or analyzed during this study are included in this published article. And the primary data could be achieved from the corresponding author.
References
Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, Kalia K, Mandoli A. Overview of oral cavity squamous cell carcinoma: risk factors, mechanisms, and diagnostics. Oral Oncol. 2021;121:105451.
Quadri P, McMullen C. Oral cavity reconstruction. Otolaryngol Clin North Am. 2023;56:671–86.
Ritschl LM, Singer H, Clasen FC, Haller B, Fichter AM, Deppe H, Wolff KD, Weitz J. Oral rehabilitation and associated quality of life following mandibular reconstruction with free fibula flap: a cross-sectional study. Front Oncol. 2024;14:1371405.
Zhong LP, Zhang CP, Ren GX, Guo W, William WN Jr, Sun J, Zhu HG, Tu WY, Li J, Cai YL, Wang LZ, Fan XD, Wang ZH, Hu YJ, Ji T, Yang WJ, Ye WM, Li J, He Y, Wang YA, Xu LQ, Wang BS, Kies MS, Lee JJ, Myers JN, Zhang ZY. Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma. J Clin Oncol. 2013;31:744–51.
Chaukar D, Prabash K, Rane P, Patil VM, Thiagarajan S, Ghosh-Laskar S, Sharma S, Pai PS, Chaturvedi P, Pantvaidya G, Deshmukh A, Nair D, Nair S, Vaish R, Noronha V, Patil A, Arya S. D’Cruz A. Prospective phase II Open-Label randomized controlled trial to compare mandibular preservation in upfront surgery with neoadjuvant chemotherapy followed by surgery in operable oral cavity cancer. J Clin Oncol. 2022;40:272–81.
Keam B, Machiels JP, Kim HR, Licitra L, Golusinski W, Gregoire V, Lee YG, Belka C, Guo Y, Rajappa SJ, Tahara M, Azrif M, Ang MK, Yang MH, Wang CH, Ng QS, Wan Zamaniah WI, Kiyota N, Babu S, Yang K, Curigliano G, Peters S, Kim TW, Yoshino T, Pentheroudakis G. Pan-Asian adaptation of the EHNS-ESMO-ESTRO clinical practice guidelines for the diagnosis, treatment and follow-up of patients with squamous cell carcinoma of the head and neck. ESMO Open. 2021;6:100309.
Zhang Z, Wu B, Peng G, Xiao G, Huang J, Ding Q, Yang C, Xiong X, Ma H, Shi L, Yang J, Hong X, Wei J, Qin Y, Wan C, Zhong Y, Zhou Y, Zhao X, Leng Y, Zhang T, Wu G, Yao M, Zhang X, Yang K. Neoadjuvant chemoimmunotherapy for the treatment of locally advanced head and neck squamous cell carcinoma: A Single-Arm phase 2 clinical trial. Clin Cancer Res. 2022;28:3268–76.
Wu D, Li Y, Xu P, Fang Q, Cao F, Lin H, Li Y, Su Y, Lu L, Chen L, Li Y, Zhao Z, Hong X, Li G, Tian Y, Sun J, Yan H, Fan Y, Zhang X, Li Z, Liu X. Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial. Nat Commun. 2024;15:2177.
Specenier P. Immunotherapy for head and neck cancer: from recurrent/metastatic disease to (neo)adjuvant treatment in surgically resectable tumors. Curr Opin Otolaryngol Head Neck Surg. 2021;29:168–77.
Profili NI, Castelli R, Gidaro A, Merella A, Manetti R, Palmieri G, Maioli M, Delitala AP. Endocrine side effects in patients treated with immune checkpoint inhibitors: A narrative review. J Clin Med. 2023;12:5161.
Prince ADP, Huttinger ZM, Heft-Neal ME, Chinn SB, Malloy KM, Stucken CL, Casper KA, Prince MEP, Spector ME, Rosko AJ. Hypothyroidism predicts fistula development following salvage oropharyngectomy. J Otolaryngol Head Neck Surg. 2024;53:19160216241296126.
Mayland E, Curry JM, Wax MK, Thomas CM, Swendseid BP, Kejner AE, Kain JJ, Cannady SB, Miles BA, DiLeo M, McMullen C, Tasche K, Ferrandino RM, Sarwary J, Petrisor D, Sweeny L. Impact of preoperative and intraoperative management on outcomes in osteoradionecrosis requiring free flap reconstruction. Head Neck. 2022;44:698–709.
Nyirjesy SC, Zhao S, Judd R, McCrary H, Kuhar HN, Farlow JL, Seim NB, Rocco JW, Kang SY, Haring CT. Hypothyroidism as an independent predictor of 30-day readmission in head and neck cancer patients. Laryngoscope. 2023;133:2988–98.
Taylor PN, Medici MM, Hubalewska-Dydejczyk A, Boelaert K, Hypothyroidism. Lancet. 2024;404:1347–64.
Gan YY, Yang J, Zhai L, Liao Q, Huo RR. Specific depressive symptoms, body mass index and diabetes in middle-aged and older Chinese adults: analysis of data from the China health and retirement longitudinal study (CHARLS). J Affect Disord. 2025;369:671–80.
Ang SP, Chia JE, Jaiswal V, Bandyopadhyay D, Iglesias J, Mohan GVK, Gautam S, Win T, Kumar T, Iqbal A, Chia TH, Aronow W. Subclinical hypothyroidism and clinical outcomes after percutaneous coronary intervention: A Meta-Analysis. Curr Probl Cardiol. 2023;48:101719.
Rosko AJ, Birkeland AC, Bellile E, Kovatch KJ, Miller AL, Jaffe CC, Shuman AG, Chinn SB, Stucken CL, Malloy KM, Moyer JS, Casper KA, Prince MEP, Bradford CR, Wolf GT, Chepeha DB, Spector ME. Hypothyroidism and wound healing after salvage laryngectomy. Ann Surg Oncol. 2018;25:1288–95.
Huang Y, Huang Y, Chen Y, Yang Q, Yin B. Complications and hospitalization costs in patients with hypothyroidism following total hip arthroplasty. J Orthop Surg Res. 2023;18:567.
Li R, Ranganath B. Effect of hypothyroidism on short-term outcomes after autologous and implant-based breast reconstruction. Updates Surg. 2024;76:2351–9.
Li R, He T, Xing Z, Mi L, Su A, Wu W. The immune system in Hashimoto’s thyroiditis: updating the current state of knowledge on potential therapies and animal model construction. Autoimmun Rev. 2025;24:103783.
Rooney MK, Andring LM, Corrigan KL, Bernard V, Williamson TD, Fuller CD, Garden AS, Gunn B, Lee A, Moreno AC, Morrison WH, Phan J, Rosenthal DI, Spiotto M, Frank SJ. Hypothyroidism following radiotherapy for head and neck cancer: A systematic review of the literature and opportunities to improve the therapeutic ratio. Cancers (Basel). 2023;15:4321.
Daste A, Larroquette M, Gibson N, Lasserre M, Domblides C. Immunotherapy for head and neck squamous cell carcinoma: current status and perspectives. Immunotherapy. 2024;16:187–97.
Kürten CHL, Ferris RL. Neoadjuvant immunotherapy for head and neck squamous cell carcinoma. Laryngorhinootologie. 2024;103:S167–87.
Ling XW, Howe TS, Koh JS, Wong MK, Ng AC. Preoperative thyroid dysfunction predicts 30-day postoperative complications in elderly patients with hip fracture. Geriatr Orthop Surg Rehabil. 2013;4:43–9.
Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: A review. JAMA. 2019;322:153–60.
Khan MN, Russo J, Spivack J, Pool C, Likhterov I, Teng M, Genden EM, Miles BA. Association of body mass index with infectious complications in free tissue transfer for head and neck reconstructive surgery. JAMA Otolaryngol Head Neck Surg. 2017;143:574–9.
Wu Y, Zhang H, Jiang D, Yin F, Guo P, Zhang X, Zhang J, Han Y. Body mass index and the risk of abdominal aortic aneurysm presence and postoperative mortality: a systematic review and dose-response meta-analysis. Int J Surg. 2024;110:2396–410.
Landeen KC, Vittetoe KL, Smetak M, Gong W, Lindsell CJ, Wood CB, Bennett M. Predicting complications in head and neck surgery: comparing calculators to surgeons. Ear Nose Throat J. 2024. https://doi.org/10.1177/01455613241266468
Acknowledgements
None declared.
Funding
The study was supported by Henan Research Program of Medical Education (No.Wjlx2022031).
Author information
Authors and Affiliations
Contributions
Study design: WZ, PL, XL, QF. Manuscript writing: WZ, PL, XL, QF. Studies selecting: WZ, PL, XL, QF. Data analysis: WZ, PL, XL, QF. Study quality evaluating: WZ, PL, XL, QF. Manuscript revising: WZ, PL, XL, QF. The final manuscript was read and approved.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
This study was approved by Zhengzhou University Institutional Research Committee, and written informed consent for medical research was obtained from all patients prior to initial treatment. All methods were performed in accordance with relevant guidelines and regulations.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Zhang, W., Lu, P., Li, X. et al. Hypothyroidism following immunotherapy predicts more postoperative complication in oral squamous cell carcinoma. BMC Cancer 25, 643 (2025). https://doi.org/10.1186/s12885-025-14070-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12885-025-14070-7