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Clinical correlation and survival analysis of hepatitis B virus infection in oral squamous cell carcinoma: a retrospective study of 1373 patients

BMC Cancer volume 25, Article number: 801 (2025) Cite this article

Abstract

Background

Chronic hepatitis B virus (HBV) infection poses a significant global public health challenge and is found closely related to extrahepatic cancers, including head and neck cancer. Oral squamous cell carcinoma (OSCC) is the major category of head and neck cancer. This retrospective study was conducted to explore the clinical correlation and survival analysis of OSCC patients with HBV.

Methods

The study involved 1,373 patients with OSCC treated at the Hospital of Stomatology, Sun Yat-sen University from 2012 to 2022. Propensity score matching was used to analyze the clinical correlations and survival outcomes, specifically overall survival (OS) and disease-free survival (DFS), in patients with or without hepatitis B surface antigen (HBsAg) seropositivity. Subgroup analyses were conducted for both the early and advanced stages of OSCC. The benefits of neck dissection in OSCC patients with HBV infection were further investigated.

Results

The prevalence of HBV infection in our cohort was 12.0%. The HBsAg (+) group had a higher percentage of individuals under 60 (73.3% versus 63.7%, p = 0.016). Post-matching for age, sex, pathological T category, pathological N category, and neck dissection, the OSCC patients with HBsAg (+) had lower 5-year OS and DFS rates rather than HBsAg (−) patients, especially those with advanced stage and cervical lymph node metastasis. HBsAg (−) was confirmed as an independent protective prognostic indicator for both OS (hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.34–0.79; p = 0.002) and DFS (HR = 0.69, 95% CI = 0.50–0.96; p = 0.027). Notably, elective neck dissection was recognized as an independent protective factor influencing 5-year OS and DFS. While DOI and pathological N category were both confirmed as the risk factors for prognosis.

Conclusions

HBsAg is a potential prognostic marker for OSCC. It is essential to screen for HBV infection prior to initiating tumor treatment. Additionally, serological testing, antiviral prophylaxis and therapy play crucial roles in preventing HBV reactivation during the course of tumor treatment. In cases of early OSCC associated with HBV infection, elective neck dissection has been shown to reduce the rates of recurrence and metastasis significantly.

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Introduction

According to the GLOBOCAN 2022 report by the International Agency for Research on Cancer, head and neck squamous cell carcinoma (HNSCC) ranked as the eighth most common cancer diagnosed globally [1]. Among head and neck squamous cell carcinomas, oral squamous cell carcinoma (OSCC) is the most prevalent, with an estimated 390,000 new cases and 190,000 deaths annually, representing 1.9% of cancer-related deaths [1, 2]. Human papillomavirus infection (HPV) is a significant risk factor for oropharyngeal cancer within the realm of HNSCC [3]. Moreover, various cancers demonstrate a clear association with viral infections, such as Epstein-Barr virus and nasopharyngeal carcinoma (NPC), as well as hepatitis B virus (HBV)/ hepatitis C virus (HCV) and Hepatocellular carcinoma [4].

Chronic hepatitis B virus infection poses a significant global public health challenge. The latest World Health Organization (WHO) report indicates that in 2019, there were approximately 1,500,000 new cases of chronic HBV infection and 820,000 related deaths worldwide [5]. Additionally, infections led to 2.2 million new cancer cases, representing 13% of all cancer cases, with HBV specifically contributing to 360,000 new cancer cases [4]. In China, the seroprevalence of the hepatitis B surface antigen (HBsAg) across all age groups was 11.9%, 8.4%, and 7.8% in 1990, 2015, and 2019, respectively, nearly double the global average rates of 6.0%, 4.4%, and 4.1% [6]. Chen et al. [7] discovered that HBx protein enhanced the proliferation and migration of pancreatic ductal adenocarcinoma cells through the PI3K/AKT pathway. Additionally, patients with NPC who tested positive for HBsAg were more likely to experience distant metastasis, particularly in the liver [8].

Our previous meta-analysis revealed a positive correlation between HBV infection and head and neck cancer (HNC), specifically oral cancer and NPC [9]. We were particularly interested in understanding the relationship between clinical variables and HBV infection in OSCC patients, as well as the prognosis for OSCC patients with HBV infection. To delve deeper into this association, we conducted a retrospective study.

Methods

Patient selection and virus infection status

The study utilized data from the cancer registry database and medical records of the Hospital of Stomatology, Sun Yat-sen University, spanning from October 2012 to November 2022, with a follow-up period until April 30, 2024. A total of 1,654 patients with histologically confirmed squamous cell carcinoma in various oral sites were included for clinical correlation analysis. Upon admission, all patients underwent liver function, coagulation function tests, and infectious disease screening, including HBV, HCV, treponema pallidum (TP), and human immunodeficiency virus (HIV) with the chemiluminescence method. Patients with positive HBsAg were classified as infected, those with HBsAg (−) and positive hepatitis B core antibody (HBcAb) were considered past infected, and those negative for both were deemed uninfected. Both past infected and uninfected patients were HBsAg (−), while infected and past infected patients were HBcAb (+). Cancer staging follows the American Joint Committee on Cancer TNM staging classification (eighth edition). This study was conducted in accordance with the Declaration of Helsinki. The study has received ethical approval from the Medical Ethics Committee of the Hospital of Stomatology, Sun Yat-sen University (Approval Number: ERC- [2017]-26).

Clinical correlation analysis and survival analysis

The workflow of the study is displayed in Fig. 1. A total of 281 patients with HIV, HCV, TP infection, or a history of cancer were excluded from the study. Demographic characteristics, clinical data (pathological T and N category, depth of invasion [DOI], extranodal extension [ENE], prognostic stage, histologic grade, and neck dissection), and blood test results of 1,373 patients were collected for clinical correlation analysis. Among these, 453 patients were excluded due to insufficient data (clinical data, n = 107 and follow-up data, n = 330) or short follow-up duration (less than 30 days, n = 16). Kaplan-Meier survival curves were used to assess the impact of HBsAg (+) on overall survival (OS) and disease-free survival (DFS) in patients with OSCC. Propensity score matching (R [version 4.3.2], ‘MatchIt’ [version 4.5.5], caliper value = 0.25) was employed to include 920 patients, matched for age, sex, pathological T (pT) category, pathological N (pN) category, and neck dissection, in order to minimize confounding factors. A stepwise selection method was employed for multivariable Cox proportional hazards analysis, incorporating all variables from the univariable analysis into the final regression model in 920 OSCC patients. OS was defined as the time from operation to the last follow-up or death, while DFS was defined as the time from operation to disease progression (recurrence and metastasis) or death.

Fig. 1
figure 1

The workflow of the study

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Subgroup analysis

To further explore the relationship between OSCC and HBV, a subgroup analysis was performed. Initially, a survival analysis was conducted on the advanced OSCC patients, specifically those with cervical lymph node metastasis (pTxN1−3), utilizing the propensity score matching method at a ratio of 1:3. Subsequently, 558 patients with early-stage OSCC (pT1 − 2N0) were selected to examine the impact of neck dissection. Finally, we assessed the benefits of different approaches to neck dissection among OSCC patient groups with varying HBV infection statuses.

Statistical analysis

All statistical analyses were conducted using R (version 4.3.2), employing packages such as ‘MatchIt’, ‘survival’, and ‘survminer’. Categorical variables were compared using the chi-square and Fisher exact tests, while continuous variables between groups were evaluated using the Kruskal-Wallis H test. Survival analysis was performed utilizing the Kaplan-Meier method, and group differences along with pairwise comparisons within each group were evaluated using the log-rank test. Univariate and multivariate hazard ratios for 5-year OS and DFS with the Cox proportional hazards model were utilized to determine the independent significance of variables. The significance level was set at p < 0.05.

Result

Characteristics and clinical correlation analysis in OSCC patients with different HBV status

The demographic, oncological, and hepatic profiles of the 1,373 enrolled patients were outlined in Table 1. The prevalence of HBV infection in our cohort was 12.0%. The median age at OSCC diagnosis for the entire cohort was 54 years. A male predominance was noted (63.4%). The majority of patients were initially diagnosed at an early stage. The median follow-up duration was 35.0 months (interquartile range: 19.0–57.6 months). During the follow-up period, mortality rates were 19.7% for the overall group, 33.7% for the HBsAg (+) cohort, and 17.9% for the HBsAg (−) cohort. The infected patients had a higher percentage of individuals under the age of 60 (73.3%, p = 0.003) and male (69.7%, p = 0.007). More patients in the HBsAg (−) group underwent elective neck dissection compared to the HBsAg (+) group (p = 0.015). However, there were no significant differences between the two groups in terms of the history of tobacco and alcohol use, pT category, pN category, DOI, ENE, prognostic stage, and histologic grade. In blood test results, the alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), thrombin time (TT), Fibrinogen (FIB), and international normalized ratio (INR) showed statistical differences between HBsAg (+) and HBsAg (−) groups. While no significant difference was observed in gamma-glutamyl transferase (GGT) and activated partial thromboplastin time (APTT) (Supplementary Table 1). In groups categorized by varying infection statuses, the infected patients exhibited outcomes akin to those observed in the HBsAg (+) cohort.

Table 1 Baseline characteristics of the OSCC patients with different HBV infection status before and after matching
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Influence of chronic HBV infection on prognosis in OSCC

A total of 920 patients with OSCC were categorized into three groups based on their HBsAg and HBcAb status: uninfected patients, past infected patients, and currently infected patients. Patients with active HBV infection had the poorest prognosis, as evidenced by lower OS and DFS rates compared to uninfected and past infected patients (Fig. 2A, B; OS, p = 0.013; DFS, p = 0.034). Specifically, HBsAg (+) patients exhibited worse OS and DFS outcomes (Fig. 2C, D; OS, p = 0.003; DFS, p = 0.010), while there was no significant difference in survival rates between HBcAb (+) and HBcAb (−) groups (Fig. 2E, F; OS, p = 0.464; DFS, p = 0.355).

Fig. 2
figure 2

The survival analysis for OSCC patients. The Kaplan-Meier (K-M) survival analysis among infected patients (HBsAg [+] + HBcAb [+]), past infected patients (HBsAg [−] + HBcAb [+]), and uninfected patients (HBsAg [−] + HBcAb [−]) (A, B). The K-M survival analysis between HBsAg (+) and HBsAg (−) patients (C, D). The K-M survival analysis between HBcAb (+) and HBcAb (−) patients (E, F)

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To minimize potential confounding factors such as age, sex, pT category, pN category, and neck dissection, propensity score matching was employed. Post-matching, the HBsAg (+) group (n = 102) and HBsAg (−) group (n = 204) demonstrated similar characteristics (Table 1). These results highlighted the negative impact of HBV infection on the survival of OSCC patients. The 5-year OS rates were 65.8% for the HBsAg (+) group and 77.7% for the HBsAg (−) group (Fig. 3A, p = 0.008), with corresponding 5-year DFS rates of 60.1% and 46.9%, respectively (Fig. 3B, p = 0.048).

Fig. 3
figure 3

The survival analysis for propensity score matching analysis and subgroup analysis. The Kaplan-Meier (K-M) survival analysis between HBsAg (+) and HBsAg (−) patients by using the propensity score matching method (A, B). The K-M survival analysis in advanced-stage OSCC patients with and without HBV infection (C, D). The K-M survival analysis in OSCC patients with cervical lymph node metastasis between HBsAg (+) and HBsAg (−) group (E, F). The impact of neck dissection in early-stage OSCC patients with and without HBV infection (G, H). The Kaplan-Meier (K-M) survival analysis in HBsAg (+), HBcAb (+) patients with or without neck dissection (I, J). The Kaplan-Meier (K-M) survival analysis in HBsAg (−), HBcAb (+) patients with or without neck dissection (K, L)

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Independent prognostic factors for OSCC

After analyzing clinical parameters, we identified several factors associated with 5-year OS and DFS as presented in Table 2. HBsAg (−) was confirmed as an independent protective prognostic indicator for both OS (hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.34–0.79; p = 0.002) and DFS (HR = 0.69, 95% CI = 0.50–0.96; p = 0.027). While pN category was identified as a risk factor for OS (HR = 3.32, 95% CI = 2.13–5.18; p < 0.001) and DFS (HR = 2.22, 95% CI = 1.60–3.10; p < 0.001). Additionally, age (HR = 1.47, 95% CI = 1.08–2.01; p = 0.015) was recognized as an independent risk predictor for 5-year OS. Notably, both elective neck dissection (HR = 0.55, 95% CI = 0.35–0.86; p = 0.009 for OS; HR = 0.48, 95% CI = 0.35–0.65; p < 0.001 for DFS) and therapeutic neck dissection (HR = 0.55, 95% CI = 0.33–0.90; p = 0.018 for OS; HR = 0.48, 95% CI = 0.34–0.69; p < 0.001 for DFS) were recognized as the independent protective factors influencing 5-year OS and DFS. DOI (HR = 2.50, 95% CI = 1.45–4.31; p = 0.047 for OS; HR = 1.99, 95% CI = 1.38–2.88; p < 0.001 for DFS) was confirmed as the risk factors for prognosis. Although pT category, PT, and INR were associated with poor prognosis in OSCC, they did not emerge as independent prognostic factors in multivariate analysis. The variability observed in ENE may be attributed to our small sample size, which can introduce randomness due to individual sample differences.

Table 2 The univariate and multivariate Cox regression analysis for 5-year overall survival and disease-free survival of OSCC patients
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Subgroup analysis in early and advanced OSCC

Similarly, the propensity score matching method was utilized to mitigate the influence of confounding variables. All baseline characteristics were equilibrated and presented in Supplementary Tables 2 and 3. In advanced OSCC, patients who tested negative for HBsAg had superior OS (p = 0.022; Fig. 3C) compared to those who tested positive for HBsAg, although a similar trend was observed for DFS with no significant difference (p = 0.239; Fig. 3D). Notably, the HBsAg-negative group demonstrated a more favorable survival outlook than the HBsAg-positive group in OSCC cases with cervical lymph node metastasis (OS, p = 0.020; DFS, p = 0.022; Fig. 3E, F).

In the early-stage OSCC, patients who tested negative for HBsAg and underwent neck dissection exhibited the most favorable prognosis, whereas those who tested positive for HBsAg and did not undergo neck dissection had poorer OS (p = 0.004; Fig. 3G) and DFS (p < 0.001; Fig. 3H). Pairwise comparisons showed that neck dissection could improve the DFS of early OSCC. Subsequently, we compared the effectiveness of various neck dissection options among populations with differing HBV infection statuses. In patients with a history of past infections, elective neck dissection demonstrated greater benefits compared to observation (p < 0.001, Fig. 3K, L), significantly reducing the likelihood of recurrence and metastasis. Similar trends were observed in infected patients (p = 0.064, Fig. 3I, J). However, the differences might not be statistically significant due to the limited sample size.

Discussion

Hepatitis B virus, a virus with a preference for the liver, can cause persistent and chronic infections leading to complications within and beyond the liver, posing a significant global public health challenge [10]. Recent studies [11] have demonstrated the presence of HBV DNA or protein in tumors and tissues outside the liver, such as pancreatic cancer [7, 12], gastric cancer [12,13,14], lymphocytes [14], and salivary gland tumors [15], suggesting that the hepatotropic nature of the virus may not be strict. Numerous studies have consistently highlighted a strong association between HBV infection and various extrahepatic tumors [12, 16, 17] including head and neck cancer [9], pancreatic cancer [18], gastric cancer [13], cholangiocarcinoma [19], and colorectal cancer [20].

In our previous study on HNSCC, we observed a high concurrent risk of HBV infection in patients with oral cancer, aligning with the findings of our retrospective study [9]. The infection rate of 12.0% surpassed the average levels observed in China (8.4% in 2015 and 7.8% in 2019) [6] and South China (8.8% in 2015) [21]. Interestingly, patients infected with HBV tended to be diagnosed with OSCC at a younger age, mirroring findings in research on gastric cancer [22], pancreatic cancer [14], and nasopharyngeal carcinoma [23]. These findings suggested a potential influence of HBV on the onset and progression of OSCC through mechanisms that remained unknown. Despite this, we did not observe a significant correlation between TNM stage and HBV infection in OSCC. Lai et al. [24] highlighted that HBV infection had a significant impact on OS and PFS prognosis in HNC. Consistent with this, our study revealed that HBsAg (+) patients, particularly those in advanced stages with lymph node metastasis, exhibited poorer OS and DFS compared to HBV-negative patients with OSCC. The higher mortality rate among HBV-infected patients was attributed to a higher proportion of advanced cases (62.9%) [24], while the survival rate was higher in our cohort due to a larger percentage of early-stage patients (over 65%). Additionally, elective neck dissections emerged as an independent protective factor for DFS in OSCC patients with HBV infection, this was also consistent with the results of the meta-analysis [25].

According to the National Comprehensive Cancer Network (NCCN) Oncology Clinical Practice Guidelines [26], screening for hepatitis B is recommended for patients with OSCC prior to initiating systemic treatment. Findings of chronic HBV (HBsAg [+]) or past HBV (HBsAg [−] and HBcAb [+]) infection necessitate an assessment of the risk for HBV reactivation [27]. However, there remains a deficiency of high-quality clinical studies to substantiate evidence-based management of HBV infection in the context of OSCC treatment.

Hepatitis B virus reactivation has garnered increasing attention in the context of tumor treatment, particularly in relation to chemotherapy and immunotherapy [28, 29]. Zhang et al. reported that 2 out of 35 patients with nasopharyngeal carcinoma (NPC) experienced HBV reactivation following anti-PD-1/PD-L1 therapy. Additionally, HBsAg-positive patients who did not receive antiviral prophylaxis were found to be at a higher risk of HBV reactivation (Odd Ratio = 17.50, 95% CI = 1.95-157.07, p = 0.004) [30]. At present, the treatment failure in OSCC is primarily linked to local recurrence and cervical lymph node metastasis [3, 31]. According to the NCCN Guidelines [26], the standard approach for most advanced OSCC patients involves concurrent radiotherapy and systemic therapy. The reactivation of HBV presents a significant concern [32, 33], potentially leading to liver damage that could disrupt treatment [34] due to the hepatotoxicity of chemotherapy drugs and the metabolism of these drugs in the liver [35]. Additionally, alterations in coagulation function could impact the recovery of postoperative wounds and elevate the risk of infection. Furthermore, it has been reported that coagulation and fibrinolytic factors might be linked to intrahepatic metastasis of hepatocellular carcinoma [36]. While tumor immunotherapy, such as immune checkpoint inhibitor (ICI) therapy, is gaining attention in recurrent or metastatic HNSCC [37], there is insufficient evidence to support the idea that ICI treatment could trigger HBV reactivation [38]. Therefore, further research is essential to evaluate HBV screening and prophylaxis for OSCC patients before initiating immunosuppressive therapies.

A recent study found that HBV DNA polymerase upregulated the transcription of PD-L1 and suppressed T cell activity, facilitating immune evasion in hepatocellular carcinoma [39]. In the context of chronic HBV infection, effector CD8 + T cells exhibited various degrees of an ‘exhausted’ phenotype, as demonstrated in multiple human and animal studies [40]. Furthermore, myeloid-derived suppressor cells in patients with chronic hepatitis B were significantly elevated compared to those in healthy controls [41]. These alterations in the immune microenvironment induced by the hepatitis B virus facilitate the occurrence and progression of malignant tumors. However, limited research has been conducted on the association between OSCC and HBV infection, with no prior documentation of HBV-related proteins or DNA in OSCC tissue. In contrast, previous studies have identified the presence of HBx protein and mRNA in adenoid cystic carcinoma and Warthin’s tumor [15]. Notably, HBV has been shown to persist in salivary glands, with viral DNA frequently detected in saliva through PCR analysis [11, 42]. This observation leads to the hypothesis that the presence of HBV in saliva may influence the immune microenvironment of the oral cavity, potentially contributing to the development of oral tumors [43]. Moreover, Chen et al. found that community-wide changes of fecal microbiota in liver cirrhosis are observed compared with healthy controls, and Fusobacteria are highly enriched in the cirrhosis group [44]. Fusobacterium nucleatum, long known as a constituent of the oral microflora, has garnered attention for its association with oral cancer [45], colorectal cancer [46], and breast cancer [47, 48]. Therefore, the changes of oral flora in patients with chronic hepatitis B infection are also worth in-depth study.

To our knowledge, this is the first article to explore the clinical correlation and survival analysis of OSCC patients with HBV infection. Nevertheless, this study had several limitations. Firstly, as a single-center retrospective study, selection bias and observation bias were inevitable, such as the loss to follow-up of approximately 30% of patients and the low proportion of pN3 category patients. Secondly, we controlled for interference from most infectious diseases such as HCV, TP, and HIV. However, since HPV testing was not a routine procedure for OSCC patients, the potential impact of HPV cannot be completely ruled out. Moreover, the DNA level of HBV was not tested upon admission of the patient, making it impossible to further investigate the impact of different DNA levels on OSCC. Thirdly, due to limitations in medical records and follow-up, detailed information on radiotherapy, chemotherapy, and antiviral treatment for patients was not available, leading to a gap in the stratified study. The final and most crucial point was that, due to incomplete pathological reports, adverse pathological features such as resection margins, worst pattern of invasion, perineural invasion, and lymphovascular invasion, were not included in this study. This omission might obscure the association between HBV and adverse pathological features. Moving forward, high-quality cohort studies are needed to further explore and validate our research findings.

In conclusion, HBsAg is a potential prognostic marker for OSCC. It is essential to screen for HBV infection prior to initiating tumor treatment. Additionally, serological testing, antiviral prophylaxis and therapy play crucial roles in preventing HBV reactivation during the course of tumor treatment. In cases of early OSCC associated with HBV infection, elective neck dissection has been shown to significantly reduce the rates of recurrence and metastasis.

Data availability

The data are not publicly available for privacy or ethical restrictions but are available upon reasonable request. A proposal with detailed description of study objectives and statistical analysis plan will be needed for evaluation of the reasonability of requests. Additional materials might also be required during the process of evaluation. Deidentified participant data will be provided after approval from the corresponding author and study center.

Abbreviations

HNSCC:

head and neck squamous cell carcinoma

OSCC:

oral squamous cell carcinoma

HPV:

Human papillomavirus

NPC:

nasopharyngeal carcinoma

HBV:

Hepatitis B virus

HCV:

hepatitis C virus

WHO:

World Health Organization

HBsAg:

hepatitis B surface antigen

HNC:

head and neck cancer

STROBE:

Reporting of Observational Studies in Epidemiology

TP:

Treponema pallidum

HIV:

human immunodeficiency virus

HBcAb:

hepatitis B core antibody

DOI:

depth of invasion

ENE:

extranodal extension

pT:

pathological T

pN:

pathological N

OS:

overall survival

DFS:

disease-free survival

VIF:

variance inflation factor

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

PT:

prothrombin time

TT:

thrombin time

FIB:

Fibrinogen

INR:

international normalized ratio

GGT:

gamma-glutamyl transferase

APTT:

activated partial thromboplastin time

HR:

hazard ratio

CI:

confidence interval

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Acknowledgements

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China (No.82103558) and Clinical Research Fund for Western Stomatology of the Chinese Stomatological Association (No. CSA-W2022-06).

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Author notes

  1. Rukeng Tan, Yiyao Zhu and Zengyu Chen authors have contributed equally to this work and share the first authorship.

  2. Le Yang and Guiqing Liao contributed equally to this work.

Authors and Affiliations

  1. Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, Guangzhou, 510055, Guangdong, China

    Rukeng Tan, Yiyao Zhu, Zengyu Chen, Xinkai Feng, Yujie Liang, Sien Zhang, Guiqing Liao & Le Yang

  2. Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China

    Rukeng Tan, Yiyao Zhu, Zengyu Chen, Xinkai Feng, Yujie Liang, Sien Zhang, Guiqing Liao & Le Yang

  3. The First People’s Hospital of Kashi Area, Xinjiang Uygur Autonomous Region, No.120, Yingbin Avenue, Kashi, People’s Republic of China

    Nuerbiya Abuduxiku

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  1. Rukeng Tan
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Contributions

Conceptualization: Le Yang, Guiqing Liao, Rukeng Tan, Yujie Liang. Methodology: Rukeng Tan, Yiyao Zhu, Le Yang.Data curation: Rukeng Tan, Yiyao Zhu, Nuerbiya •Abuduxiku.Formal analysis: Zengyu Chen, Xinkai Feng. Investigation: Yiyao Zhu, Sien Zhang, Nuerbiya •AbuduxikuVisualization: Rukeng Tan, Zengyu Chen.Funding acquisition: Le Yang, Nuerbiya •Abuduxiku.Writing– original draft: Rukeng Tan, Zengyu Chen.Writing– review & editing: Le Yang, Yiyao Zhu, Rukeng Tan, Zengyu Chen. Project administration: Le Yang, Yujie Liang.Supervision: Guiqing Liao, Le Yang.

Corresponding authors

Correspondence to Guiqing Liao or Le Yang.

Ethics declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki. Ethical approval for this study was obtained from the Medical Ethics Committee of the Hospital of Stomatology, Sun Yat-sen University (Approval No.: ERC-[2017]-26). This retrospective study was conducted in accordance with “Ethical Review Measures for Biomedical Research Involving Human Subjects” promulgated by the Chinese government. According to the regulations of the Ethical Committee of the Hospital of Stomatology, Sun Yat-sen University and the data usage requirements of biomedical databases, informed consent can be waived for this retrospective study.

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The authors declare no competing interests.

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Tan, R., Zhu, Y., Chen, Z. et al. Clinical correlation and survival analysis of hepatitis B virus infection in oral squamous cell carcinoma: a retrospective study of 1373 patients. BMC Cancer 25, 801 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12885-025-14188-8

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BMC Cancer

ISSN: 1471-2407

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