Nasopharyngeal carcinoma: clinicoepidemiology and treatment outcomes at a major Australian tertiary referral hospital

Introduction

Malignancies of the nasopharynx are rare and encompass various epithelial and non-epithelial tumours including lymphoma, myeloma, sarcoma, and salivary gland tumours. Within this anatomical region, the most common malignant lesions are nasopharyngeal carcinomas (NPCs) which originate from squamous epithelial cells, particularly at the fossa of Rosenmüller (1). NPC shows significant epidemiological variation across different ethnicities and geographic regions, with higher prevalence rates in East and Southeast Asia, the Middle East, and North Africa compared to developed Western countries (2). In Australia, the age-standardised incidence rate was only 0.7 per 100,000 in 2023 (3), whereas NPC contributes significantly to the overall cancer burden in endemic areas with rates reaching 3–15 per 100,000 (4). Although the pathogenesis of NPC remains unclear, it is likely multifactorial involving genetic susceptibility, environmental factors, and prior Epstein-Barr virus (EBV) infection (5). Studies have shown that the non-keratinising histological subtypes of NPC account for most cases in endemic regions and are invariably linked to EBV, whereas the keratinising subtype occurs more frequently in non-endemic regions and is associated with tobacco and alcohol use (6,7). Current literature on the clinicoepidemiology and histopathology of NPC is concentrated in high incidence regions, whilst data from non-endemic areas involving lower risk patients remains limited (8).

NPC is often diagnosed at advanced stages, owing in part to its subtle clinical presentation and difficult accessibility behind the nasal cavity, leading to many patients presenting with advanced stage disease and resulting in a poor prognosis with a 5-year survival rate of 49% in patients with systemic metastases (9). Improvements in the treatment paradigm for NPC has seen the usage of combination radiotherapy and chemotherapy with better outcomes and patient tolerability, but locoregional and distant recurrences remain common and further contribute to poor survival (10). Due to limited experiences in NPC management, Australian treatment strategies have been primarily guided by overseas studies, which fail to account for potentially distinct responses in Australia’s multicultural patient population. Immigration has increased the Asian populace in Sydney over the past two decades, leading to a gradual rise in NPC incidence and greater patient heterogeneity (3,11).

The aim of this study is to describe the long-term management of NPC in Australia and compare the clinicoepidemiology and treatment outcomes of patients from endemic and nonendemic backgrounds. By expanding upon existing data from other non-endemic regions, further research may uncover unique ethnicity-dependent mechanisms underpinning disease pathogenesis and therapeutic response, ultimately advancing NPC detection and treatment.

Methods

Study design

This retrospective cohort study included patients who attended the Northern Sydney Cancer Centre (NSCC) at Royal North Shore Hospital (RNSH), a major tertiary hospital in Sydney, Australia between December 1^st 2001 to March 31^st 2024. Data were extracted from the NSCC database which incorporates clinical questionnaires, consultation notes, and investigation reports. Key variables included demographics (age, sex, ethnicity, medical comorbidities, alcohol use, smoking status, family history), clinicopathology (tumour histology and EBV status, primary disease site, metastases, staging), treatment (intent, protocol, completion rate, side effects), and follow-up outcomes (recurrence timing and location, salvage treatment, death). Patient follow-up occurred as part of routine cancer surveillance involving three-monthly reviews for 2 years and six-monthly thereafter until 5 years. The study is reported according to the STROBE reporting guidelines (available at https://www.theajo.com/article/view/10.21037/ajo-25-17/rc).

Retention of original reports and use of standardised diagnostic criteria minimised recall and misclassification biases. Clinical staging and histological subtyping were performed for NPC only, using respectively the American Joint Committee on Cancer (AJCC) 8^th edition guidelines and the World Health Organization (WHO) criteria: keratinising (type I), non-keratinising differentiated (type II), and non-keratinising undifferentiated (type III). The rare basaloid variant of NPC was described but excluded from statistical analyses concerning histopathology. Tumour EBV status was determined via EBV-encoded RNA in-situ hybridisation (EBER-ISH) tests. Patient ethnicities were broadly categorised as Asian and non-Asian to reflect endemicity patterns and ensure statistical power. Asian ethnicity was defined as natives of the Asian continent or of Asian descent, and was determined through self-identified ancestry tracing by patients at the time of their initial clinic registration.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Northern Sydney Local Health District Human Research Ethics Committee (EC00112; approval ID: 2023/ETH01453). All data has been consented for storage and research use via implicit patient consent with an opt-out option.

Patient eligibility

All NSCC patients with nasopharyngeal masses were assessed for eligibility (Figure 1). The inclusion criteria for initial demographical and clinicopathological analyses required a biopsy-confirmed nasopharyngeal malignancy. Patients with incorrect diagnoses or insufficient data for disease staging and classification were excluded. For treatment and outcomes analysis, additional exclusion criteria were applied: (I) non-NPC diagnoses; (II) treatment at other institutions; and (III) treatment with palliative intent.

Figure 1 Patient eligibility flowchart. Red outlines denote patients that form each study population. Dotted outlines denote outcomes analysed. RNSH, Royal North Shore Hospital.

Statistical analysis

Demographical and clinicopathological characteristics were compared between NPC and non-NPC patients, and between Asian and non-Asian NPC patients. Group differences were analysed with Chi-squared/Fisher tests for nominal variables and Mann-Whitney U tests for continuous variables. Time to event (TTE) was measured from treatment completion. Disease-specific survival (DSS) was defined as time to death from cancer or treatment complications, whereas intercurrent causes were censored. Relapse-free survival (RFS) was defined as time to first recurrence or death from any cause. Patients lost to follow up were censored at the timepoint of their last consultation. Univariate Cox regression models [95% confidence interval (CI)] identified prognostic factors for RFS, with P<0.15 variables selected for multivariate analysis using the enter method. Variables were grouped if the number of events or patients with corresponding characteristics were low and demonstrated similar survival outcomes. The Kaplan-Meier method was used to construct TTE curves and estimate median survival times. An alpha value of 0.05 was set as the threshold for statistical significance. Missing data were handled via multiple imputation after being assessed as missing at random. Analyses were conducted in SPSS Statistics 29 (IBM Corp., Armonk, N.Y., USA) and graphs constructed in GraphPad Prism 10 (GraphPad Software, Boston, MA, USA).

Results

A total of 132 patients were identified in the database with a nasopharyngeal mass diagnosed during the study period. Of the 118 patients meeting the inclusion criteria listed in Figure 1, 103 (87.3%) had biopsy-proven NPC. The remaining cases included lymphoma (n=5), adenoid cystic carcinoma (n=4), sinonasal undifferentiated carcinoma (n=2), extramedullary plasmacytoma (n=2), and sarcoma (n=2). Among NPC patients, 79 (76.7%) underwent definitive treatment at RNSH and had outcomes assessed, while 14 (13.6%) were treated elsewhere, 7 (6.8%) received palliative care (five of whom were of Asian ethnicity), and 3 (2.9%) declined treatment.

Patient characteristics

Most NPC patients were of Asian descent (n=75; 72.8%), primarily from East Asian countries/regions (n=52; 50.5%) including China and Hong Kong. Among non-Asian patients, three were of Middle Eastern ancestry, with the remainder predominantly of European or Anglo-European background. The median age was 55.1 [interquartile range (IQR), 44.2–62.7] years and was broadly similar between non-Asian (57.3 years) and Asian patients (53.8 years). Peak incidence was also comparable (60–69 vs. 50–59 years), with no statistically significant differences (U =0.26; P=0.80). Males were disproportionately affected (n=77; 74.8%) resulting in a male-to-female ratio of 2.96, but showing no significant ethnic variation [χ² (1, n=103) =1.11; P=0.32]. A positive family history of head and neck cancers was rare, observed in only 10 patients (9.7%), of whom 9 (90%) were Asian. Smoking was reported by 40 patients (38.8%), including 6 active (5.8%) and 34 former smokers (33.0%), while 41 patients (39.8%) regularly consumed alcohol. Non-Asians were significantly more likely to have smoked [χ² (1, n=103) =5.61; P=0.018] or consumed alcohol [χ² (1, n=103) =15.29, P<0.001]. Baseline characteristics are summarised in Table 1.

Comparison of clinicopathology between Asian and non-Asian NPC patients

NPC comprised a greater proportion of nasopharyngeal malignancies in Asian compared to non-Asian patients [n=75 (96.2%) vs. n=28 (70.0%); χ² (1, n=118) =16.30, P<0.001]. Across both cohorts, eight cases of NPC were WHO type I (7.8%), 22 were WHO type II (21.4%), 71 were WHO type III (68.9%), and 2 were basaloid NPC (1.9%). While non-keratinising undifferentiated NPC predominated in both groups, keratinising NPC was relatively more frequent in non-Asians; however, overall histological distributions did not differ significantly [χ² (2, n=101) =3.14; P=0.18] (Table 2). Smoking was associated with a higher prevalence of keratinising NPC (14.9% vs. 3.3% in non-smokers), peaking among active smokers [35.1%; χ² (1, n=101) =4.46; P=0.035]. After multiple imputation, EBER-ISH positivity was significantly higher in Asian patients [χ² (1, n=101) =4.76; P=0.033] and in non-keratinising NPC variants (type II: 87.3% and type III: 90.3%) compared to keratinising NPC [56.3%; χ² (1, n=101) =4.18; P=0.045].

Most patients presented with locoregionally advanced disease [stages III: 28 (27.2%), IVa: 31 (30.1%)] with no significant ethnic differences [χ² (4, n=103) =2.38; P=0.69]. Regarding tumour node metastasis (cTNM) classification, the majority had early T stages: 36 were classified as T₁ (35.0%), 30 as T₂ (29.1%), 15 as T₃ (14.6%), and 22 as T₄ (21.4%). Lymph node involvement (N_1–3) was reported in 81 patients (78.6%) (Table 2). Distant metastases were detected in nine patients (8.7%), most commonly in bone (n=9; 100%), liver (n=3; 33.3%), and lung (n=2; 22.2%). Concomitant metastases to the ileum and laryngeal cartilages were each reported in one patient.

Treatment outcomes

Seventy-nine patients were treated with curative intent at RNSH, with 69 (87.3%) receiving both chemotherapy and radiotherapy, while 10 (12.7%) underwent radiotherapy alone. Chemotherapy regimens included concurrent chemoradiotherapy in 38 (48.1%) patients, neoadjuvant chemotherapy alone in 3 (3.8%), and neoadjuvant plus concurrent chemotherapy in 28 (32.9%). Adjuvant chemotherapy was administered in 4 (5.1%) cases, and 3 (3.8%) patients underwent surgical resection. Cisplatin was the most common concurrent agent used in 57 (86.4%) cases, whilst docetaxel-cisplatin-fluorouracil (n=11; 35.5%) and cisplatin-fluorouracil (n=10; 32.3%) were the most frequent neoadjuvant regimens (Table 3). Completion rates for the full radiation dose (66–70 Gray in 33–35 fractions) were high with 77 (97.5%) patients finishing the course, despite one treatment-related and one unrelated fatality. Acute radiation toxicities were frequent, with 72 (91.1%) patients reporting fatigue, 68 (86.0%) with dysphagia, 67 (84.8%) with mucositis, and 65 (82.3%) with dermatitis. Late or persisting toxicities included xerostomia in 75 (94.9%) patients, dysgeusia in 71 (89.9%), hearing impairment in 34 (43.0%), neck fibrosis in 25 (31.6%), and hypothyroidism in 14 (17.7%).

At 12 weeks post-treatment, 75 (94.9%) patients achieved complete metabolic response on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) [n=54 (94.7%) Asians vs. n=21 (95.5%) non-Asians]. The median follow-up duration was 62.3 months (95% CI: 56.1–74.5), totalling 401.0 person-years. The 5-year DSS was 89.7%, with survival rates of 100% for stages I–II and 83.8% for stages III–IV [χ² (1, n=56) =4.61; P=0.032; Figure 2A]. The 5-year RFS was 72.4%, significantly higher in stages I–II (90.5%) than stages III–IV [62.2%; χ² (1, n=56) =4.49; P=0.034; Figure 2B]. Univariate and multivariate Cox regression identified unfavourable prognostic factors for 5-year RFS, including Asian ethnicity [hazard ratio (HR) =4.73; 95% CI: 1.01–22.29; P=0.049], advanced T stage (T₄ vs. T_1–2; HR =4.60; 95% CI: 1.52–13.96; P=0.007), and distant metastases at diagnosis (HR =7.85; 95% CI: 1.45–42.67; P=0.017). Patient age, sex, smoking and alcohol usage during initial visit, tumour histology and EBV status, nodal involvement, and treatment protocol were not significantly associated with RFS (Table 4).

Figure 2 Five-year treatment outcomes for NPC patients treated at Royal North Shore Hospital, stratified by clinical stage. (A) DSS and (B) RFS curves are shown for early-stage (I–II, blue) and advanced-stage (III–IV, red) disease. Kaplan-Meier estimates demonstrate superior DSS and RFS among patients with early-stage NPC. The number of patients at risk at each time point is indicated below the x-axis. DSS, disease-specific survival; NPC, nasopharyngeal carcinoma; RFS, relapse-free survival.

Patients with recurrent disease had a median age of 52.6 years at the time of relapse (IQR, 43.1–58.2) years. Among them, 15 experienced locoregional recurrence while three had distant recurrence. The most common distant sites were the lungs (n=3), followed by bone (n=1). Six patients (33.3%) recurred within 2 years, while 5 (27.8%) had late recurrences beyond 5 years (range, 74.6–117.3 months). Salvage management was multimodal involving chemotherapy (n=14), re-irradiation (n=12), surgical resection (n=7), and immunotherapy (n=4). Subsequent 5-year DSS for patients with locoregional recurrence was 36.4%, with a median survival time of 42.6 months (95% CI: 25.8–59.4).

Discussion

This Sydney-based study contributes to the current paucity of data on NPC in Australia, a non endemic region, by providing preliminary insights into ethnicity-associated differences in clinicoepidemiology such as risk factors and histopathology. These findings underscore the poorer outcomes in advanced-stage disease despite definitive treatment and suggest Asian ethnicity as a potential prognostic factor for relapse. Additionally, the reduced survival and prolonged latency of recurrent NPC illustrate the complexities of long-term disease control and highlights the importance of follow-up surveillance and early detection of recurrent disease. Overall, these insights provide a foundation for optimising management in heterogenous populations.

Asian patients comprised 72.8% of the NPC cohort, a substantial overrepresentation compared to their 17.4% share of the Australian population (12). Similar proportions have been observed in patient cohorts from other multicultural Western nations such as the United States and Canada, reaffirming the heightened risk associated with Asian ethnicity (13,14). However, NPC incidence among immigrants from endemic regions and their descendants has declined in other non-endemic countries (15,16), indicating a potential shift in the ethnic distribution of NPC cases in Australia over time. Comparing ethnicities, both non-Asian and Asian patients in this study had similar median ages and age distribution patterns with no statistically significant differences observed. In contrast, global epidemiological data show clearer trends, with NPC incidence peaking at 45–59 years in high-risk populations vs. 65–79 years in low-risk groups (2). This variability has been attributed to genetic predisposition and earlier exposure to carcinogens in Asian countries (2); consequently, shared environmental factors may have minimised differences between Asians and non-Asians in this cohort. Cancer stage distribution was also similar across ethnicities with most patients presenting with advanced disease. This trend can be related to the anatomical position of the nasopharynx, where early T_1–2 malignant lesions are relatively asymptomatic. However, staging patterns vary across other studies, with some reporting no significant differences and others identifying a higher frequency of late-stage disease in either Asians or non-Asians (17-19). These inconsistencies may reflect differences in healthcare literacy, socioeconomic status, and access to specialists, which influence diagnostic timing within study populations (20). Likewise, the histological distribution of NPC was similar between Asian and non-Asian patients. In both groups, non-keratinising carcinomas predominated. Keratinising NPC was more frequent in non-Asians (14.3%) but remained below historical estimates of 50–75% in non-endemic regions (21,22). This disparity may stem from earlier diagnostic misclassifications and evolving environmental hazards for keratinising disease such as declining cigarette use in Australia (7,16,23).

By contrast, ethnicity groups differed significantly in their association with risk factors including smoking, alcohol use, family history, and EBV infection. Higher smoking and alcohol consumption rates among non-Asian patients suggest a greater role for modifiable exposures in NPC development among low-risk ethnicities. A meta-analysis of over 30 studies found that ever-smokers have a 60% greater risk of NPC, with stronger associations in low-incidence populations (24), while alcohol shows inconsistent links but also frequently coexists with smoking in cases from non-endemic areas (25-27). Genetic predisposition remains a crucial determinant with a first-degree family history increasing risk by 4–20-fold (28). Familial clustering was observed almost exclusively among Asian patients, mirroring the higher prevalence of germline mutations identified in Asians including HLA, TERT, ITGA9, and GABBR1, whereas genetic contributors to NPC in non-Asians remain poorly characterised (29). Significantly higher rates of tumour EBER-ISH positivity were seen in Asians, possibly reflecting host genetic factors that enhance viral oncogenesis or the existence of EBV sequence variations with differing oncogenic potential (30). This is consistent with the greater prevalence of EBV-associated NPC in Asia relative to other regions and the tendency for EBV to affect Asian populations earlier, despite its near-universal prevalence (31,32). Furthermore, an association between risk factors and tumour histology was also noted, with higher rates of EBER-ISH positivity in non-keratinising carcinomas whilst keratinisation was more common in smokers. Smoking has been linked to an increased risk of developing keratinising over non-keratinising NPC (24,26,33). Additionally, significantly higher proportions of keratinising NPC in EBV-negative patients and non-keratinising NPC in EBV-positive patients have been observed (34,35). Taken together, these findings support distinct aetiology-dependent pathways for NPC carcinogenesis, analogous to lung cancer where smoking-related squamous cell carcinomas differ genetically from adenocarcinomas in nonsmokers (36).

Although NPC has favourable initial treatment outcomes (5-year DSS: 89.7%), survival drops significantly after recurrence (5-year DSS: 36.4%). Advanced primary tumour stage (T₄) and distant metastasis (M₁) were the only disease-related predictors of recurrence, with minimal variation across T_1–3 or nodal stages. The adverse impact of advanced disease on locoregional control is recognised, though studies differ on the specific T and N stages at which risk increases (37,38). Such variability, combined with limited sample sizes in each stage, may account for the absence of differences across earlier stages. Smoking did not increase recurrence risk, likely because data reflected usage at diagnosis rather than posttreatment behaviour, though other cohorts have reported a 46% higher risk of death and 77% higher recurrence among smokers (14). Meanwhile, Asian ethnicity was a predictor of NPC relapse, and although the effect size was modest, this pattern remains consistent with prior Australian studies (39,40). However, other non-endemic countries have reported comparable recurrence rates between Asians and non-Asians, with one study noting a 40–60% reduction in 5-year mortality among Asians (14,41). These discrepancies are poorly understood but may reflect differences in treatment protocols and clinical expertise across centres. All eligible patients in this cohort were discussed at multidisciplinary meetings to standardise treatment decision-making, yet variations in treatment persisted due to evolving recommendations and individual factors. This was particularly evident in the management of recurrences, where therapeutic options are inherently limited. Reirradiation is the predominant salvage modality but offers limited efficacy, constrained by radioresistant tumour clones and normal tissue dose thresholds (42,43). This correlates with the high prevalence of late toxicities after primary therapy, including xerostomia and dysgeusia (>90%), hearing impairment (43.0%), and neck fibrosis (31.6%). Despite improved precision with intensity-modulated radiotherapy, long-term outcomes remain suboptimal, with 5-year overall survival near 40% and ongoing risks of mucosal necrosis and fatal haemorrhage (43,44). Salvage surgery avoids reirradiation-related toxicity but remains technically challenging, requiring careful selection to achieve complete resection while minimising morbidity (45,46).

The strength of this study lies in its comprehensive analysis of NPC presentation and management in an Australian setting, where recent data are scarce. However, the low incidence of NPC limits sample sizes, reducing the statistical power and generalisability of findings. Case volumes were accumulated over two decades to address this, introducing potential inconsistencies due to evolving clinical practices and environmental factors. Small cohort sizes necessitated broader subgroup classifications, such as dichotomising ethnicity into Asian and non-Asian, to achieve sufficient numbers for subgroup analysis. While this approach has been utilised in other multiracial cohorts (14,42), it reduces data granularity and may obscure ethnic differences such as the elevated risk of NPC in patients of Middle Eastern ancestry. Furthermore, some estimates demonstrated wide CIs, reflecting small subgroup sizes and underscoring the need for more cautious interpretation. As this study was conducted at a single tertiary referral centre in Sydney, the cohort may not fully reflect Australian patterns of NPC given the higher proportion and growth of residents of Asian ancestry in Sydney compared with other regions (11). Future studies should leverage multicentric collaboration and prospective data collection to generate robust evidence across larger cohorts that are generalisable to the broader Australian context.

The strong association between EBV and NPC has led to the use of EBV serology and plasma DNA as effective screening and surveillance tools in endemic regions (47-49). While such strategies are not currently adopted in non-endemic settings like Australia, risk-based screening may still be feasible. Future research should explore targeted approaches using patient factors such as Asian ethnicity, middle age, male sex, smoking history, and family history to identify individuals who may benefit from EBV-based surveillance. In parallel, current follow-up practices may also warrant reconsideration. While routine clinical examination with nasoendoscopy and imaging has enabled earlier detection of asymptomatic recurrences with improved outcomes, standard follow-up typically ends at 5 years after initial treatment (50). Notably, 27.8% of recurrences in this cohort occurred beyond that period, raising important questions about the adequacy of current surveillance protocols in sufficiently capturing relapses, particularly in non-endemic regions where delayed recurrences may be under-recognised. Supporting this, a large Asian study involving over 2,000 patients reported that 8.1% of recurrences occurred beyond 5 years, while this figure was as high as 17.1% in another study involving 351 participants (51,52). Taken together, these data underscore the need to reassess the optimal duration of NPC surveillance, as extending follow-up to 7–10 years in selected patients may potentially improve recurrence detection and management.

Conclusions

This study enhances the understanding of NPC in Australia by examining its clinicoepidemiology and treatment outcomes in an ethnically diverse population. Known risk factors for NPC contribute differently to disease pathways in patients from endemic and nonendemic regions, with Asians showing higher rates of familial disease and EBV-positive tumours, while non-Asians had greater smoking and alcohol use. Recurrent disease, most frequently involving advanced-stage Asian patients, remains a key contributor to mortality and may emerge long after treatment. Improved treatments for recurrence and extended follow-up beyond 5 years in appropriate patients are crucial for better outcomes.

Acknowledgments

The author would like to thank Paula Macleod for her contributions to the provision of study materials. This manuscript was delivered as a verbal presentation at the 2025 Australian Society of Otolaryngology Head and Neck Surgery Annual Scientific Meeting (ASOHNS ASM) in Sydney, Australia on 28–30 March 2025.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://www.theajo.com/article/view/10.21037/ajo-25-17/rc

Data Sharing Statement: Available at https://www.theajo.com/article/view/10.21037/ajo-25-17/dss

Peer Review File: Available at https://www.theajo.com/article/view/10.21037/ajo-25-17/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://www.theajo.com/article/view/10.21037/ajo-25-17/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. The study was approved by the Northern Sydney Local Health District Human Research Ethics Committee (EC00112; approval ID: 2023/ETH01453). All data has been consented for storage and research use via implicit patient consent with an opt-out option.

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/.

References

1. Jicman Stan D, Niculet E, Lungu M, et al. Nasopharyngeal carcinoma: A new synthesis of literature data Exp Ther Med 2022;23:136. (Review). [Crossref] [PubMed]
2. Chang ET, Ye W, Zeng YX, et al. The Evolving Epidemiology of Nasopharyngeal Carcinoma. Cancer Epidemiol Biomarkers Prev 2021;30:1035-47. [Crossref] [PubMed]
3. Australian Institute of Health and Welfare. Cancer data in Australia. Available online: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia
4. Zhang Y, Rumgay H, Li M, et al. Nasopharyngeal Cancer Incidence and Mortality in 185 Countries in 2020 and the Projected Burden in 2040: Population-Based Global Epidemiological Profiling. JMIR Public Health Surveill 2023;9:e49968. [Crossref] [PubMed]
5. Su ZY, Siak PY, Leong CO, et al. The role of Epstein-Barr virus in nasopharyngeal carcinoma. Front Microbiol 2023;14:1116143. [Crossref] [PubMed]
6. Vaughan TL, Shapiro JA, Burt RD, et al. Nasopharyngeal cancer in a low-risk population: defining risk factors by histological type. Cancer Epidemiol Biomarkers Prev 1996;5:587-93.
7. Jia WH, Qin HD. Non-viral environmental risk factors for nasopharyngeal carcinoma: a systematic review. Semin Cancer Biol 2012;22:117-26. [Crossref] [PubMed]
8. Xing CY, Lin MQ, Luo WT, et al. The 100 most cited papers in nasopharyngeal carcinoma between 2000 and 2019: a bibliometric study. Transl Cancer Res 2023;12:848-58. [Crossref] [PubMed]
9. Surveillance, Epidemiology, and End Results (SEER) program. SEER*Explorer: An interactive website for SEER cancer statistics. Available online: https://seer.cancer.gov/explorer
10. Perri F, Della Vittoria Scarpati G, Caponigro F, et al. Management of recurrent nasopharyngeal carcinoma: current perspectives. Onco Targets Ther 2019;12:1583-91. [Crossref] [PubMed]
11. Australian Bureau of Statistics. Australia 2021 Census Community Profiles: General Community Profile. Available online: https://www.abs.gov.au/census/find-census-data/community-profiles/2021/AUS
12. Australian Bureau of Statistics. Cultural diversity: Census. Available online: https://www.abs.gov.au/statistics/people/people-and-communities/cultural-diversity-census/2021
13. Clark P, Taparra K, Miller JA. Identification of a High-Risk Population in the United States for Anti-EBV Serologic Screening for Nasopharyngeal Carcinoma. International Journal of Radiation Oncology*Biology*Physics 2024;120:S72.
14. Howlett J, Hamilton S, Ye A, et al. Treatment and outcomes of nasopharyngeal carcinoma in a unique non-endemic population. Oral Oncol 2021;114:105182. [Crossref] [PubMed]
15. Yu WM, Hussain SS. Incidence of nasopharyngeal carcinoma in Chinese immigrants, compared with Chinese in China and South East Asia J Laryngol Otol 2009;123:1067-74. review. [Crossref] [PubMed]
16. Sun LM, Epplein M, Li CI, et al. Trends in the incidence rates of nasopharyngeal carcinoma among Chinese Americans living in Los Angeles County and the San Francisco metropolitan area, 1992-2002. Am J Epidemiol 2005;162:1174-8. [Crossref] [PubMed]
17. Hamilton SN, Ho C, Laskin J, et al. Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis. Am J Clin Oncol 2016;39:575-80. [Crossref] [PubMed]
18. Su CK, Wang CC. Prognostic value of Chinese race in nasopharyngeal cancer. Int J Radiat Oncol Biol Phys 2002;54:752-8. [Crossref] [PubMed]
19. Yu D, Xu HB, Chen GP, et al. Racial Disparities in Nasopharyngeal Carcinoma Characteristics and Survival. Ear Nose Throat J 2024; Epub ahead of print. [Crossref]
20. Meng DF, Zhang HB, Liu GY, et al. Association of Socioeconomic Disparities With Nasopharyngeal Carcinoma Survival in an Endemic Area, China. Cancer Control 2023;30:10732748231188261. [Crossref] [PubMed]
21. Marks JE, Phillips JL, Menck HR. The National Cancer Data Base report on the relationship of race and national origin to the histology of nasopharyngeal carcinoma. Cancer 1998;83:582-8. [Crossref] [PubMed]
22. Chang ET, Hildesheim A. Nasopharyngeal Cancer. In: Thun M, Linet MS, Cerhan JR, et al. editors. Cancer Epidemiology and Prevention (4th ed). New York: Oxford University Press; 2017:489-504.
23. Australian Institute of Health and Welfare. Alcohol, tobacco & other drugs in Australia. Available online: https://www.aihw.gov.au/reports/alcohol/alcohol-tobacco-other-drugs-australia/contents/about
24. Xue WQ, Qin HD, Ruan HL, et al. Quantitative association of tobacco smoking with the risk of nasopharyngeal carcinoma: a comprehensive meta-analysis of studies conducted between 1979 and 2011. Am J Epidemiol 2013;178:325-38. [Crossref] [PubMed]
25. Feng R, Chang ET, Liu Q, et al. Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China. Cancer Epidemiol Biomarkers Prev 2021;30:545-53. [Crossref] [PubMed]
26. Polesel J, Franceschi S, Talamini R, et al. Tobacco smoking, alcohol drinking, and the risk of different histological types of nasopharyngeal cancer in a low-risk population. Oral Oncol 2011;47:541-5. [Crossref] [PubMed]
27. Nam JM, McLaughlin JK, Blot WJ. Cigarette smoking, alcohol, and nasopharyngeal carcinoma: a case-control study among U.S. whites. J Natl Cancer Inst 1992;84:619-22. [Crossref] [PubMed]
28. Liu Z, Chang ET, Liu Q, et al. Quantification of familial risk of nasopharyngeal carcinoma in a high-incidence area. Cancer 2017;123:2716-25. [Crossref] [PubMed]
29. Bei JX, Zuo XY, Liu WS, et al. Genetic susceptibility to the endemic form of NPC. Chin Clin Oncol 2016;5:15. [Crossref] [PubMed]
30. Tsao SW, Tsang CM, Lo KW. Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond B Biol Sci 2017;372:20160270. [Crossref] [PubMed]
31. Wong Y, Meehan MT, Burrows SR, et al. Estimating the global burden of Epstein-Barr virus-related cancers. J Cancer Res Clin Oncol 2022;148:31-46. [Crossref] [PubMed]
32. Winter JR, Jackson C, Lewis JE, et al. Predictors of Epstein-Barr virus serostatus and implications for vaccine policy: A systematic review of the literature. J Glob Health 2020;10:010404. [Crossref] [PubMed]
33. Long M, Fu Z, Li P, et al. Cigarette smoking and the risk of nasopharyngeal carcinoma: a meta-analysis of epidemiological studies. BMJ Open 2017;7:e016582. [Crossref] [PubMed]
34. Umar B, Ahmed R. Nasopharyngeal carcinoma, an analysis of histological subtypes and their association with EBV, a study of 100 cases of Pakistani population. Asian J Med Sci 2014;5:16-20.
35. Al-Anazi AE, Alanazi BS, Alshanbari HM, et al. Increased Prevalence of EBV Infection in Nasopharyngeal Carcinoma Patients: A Six-Year Cross-Sectional Study. Cancers (Basel) 2023;15:643. [Crossref] [PubMed]
36. Takamochi K, Oh S, Suzuki K. Differences in EGFR and KRAS mutation spectra in lung adenocarcinoma of never and heavy smokers. Oncol Lett 2013;6:1207-12. [Crossref] [PubMed]
37. Wang L, Guo Y, Xu J, et al. Clinical Analysis of Recurrence Patterns in Patients With Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy. Ann Otol Rhinol Laryngol 2017;126:789-97. [Crossref] [PubMed]
38. Wang M, Chen X, Zhao M, et al. Risk factors analysis of local failure following radiotherapy and chemotherapy to nasopharyngeal carcinoma. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2013;27:1187-90.
39. Wong CH, Kelly LE, Tripcony LB. Nasopharygeal carcinoma in Queensland, Australia: a review of 10 years experience. Australas Radiol 2007;51:276-82. [Crossref] [PubMed]
40. Corry J, Fisher R, Rischin D, et al. Relapse patterns in WHO 2/3 nasopharyngeal cancer: is there a difference between ethnic Asian vs. non-Asian patients? Int J Radiat Oncol Biol Phys 2006;64:63-71. [Crossref] [PubMed]
41. Stepan KO, Mazul AL, Skillington SA, et al. The prognostic significance of race in nasopharyngeal carcinoma by histological subtype. Head Neck 2021;43:1797-811. [Crossref] [PubMed]
42. Zhu D, Huang M, Fang M, et al. Induction of radioresistant nasopharyngeal carcinoma cell line CNE-2R by repeated high-dose X-ray irradiation. Int J Radiat Res 2019;17:47-55.
43. Leong YH, Soon YY, Lee KM, et al. Long-term outcomes after reirradiation in nasopharyngeal carcinoma with intensity-modulated radiotherapy: A meta-analysis. Head Neck 2018;40:622-31. [Crossref] [PubMed]
44. Fatima K, Andleeb A, Sofi MA, et al. Clinical outcome of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy in locally advanced nasopharyngeal carcinoma: Comparative study at SKIMS Tertiary Care Institute. J Cancer Res Ther 2022;18:133-9. [Crossref] [PubMed]
45. Zhao Y, Fang J, Zhong Q, et al. Surgical treatment and prognosis of recurrent and radiotherapy insensitive nasopharyngeal carcinoma. Braz J Otorhinolaryngol 2024;90:101366. [Crossref] [PubMed]
46. Tsang RK, Wei WI. Salvage surgery for nasopharyngeal cancer. World J Otorhinolaryngol Head Neck Surg 2015;1:34-43. [Crossref] [PubMed]
47. Lam WKJ, King AD, Miller JA, et al. Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions. J Natl Cancer Inst 2023;115:355-64. [Crossref] [PubMed]
48. Lou PJ, Jacky Lam WK, Hsu WL, et al. Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches. J Clin Oncol 2023;41:4257-66. [Crossref] [PubMed]
49. Yang L, Kartsonaki C, Simon J, et al. Prospective evaluation of the relevance of Epstein-Barr virus antibodies for early detection of nasopharyngeal carcinoma in Chinese adults. Int J Epidemiol 2024;53:dyae098. [Crossref] [PubMed]
50. Thamboo A, Tran KH, Ye AX, et al. Surveillance tools for detection of recurrent nasopharyngeal carcinoma: An evidence-based review and recommendations. World J Otorhinolaryngol Head Neck Surg 2022;8:187-204. [Crossref] [PubMed]
51. Chen YH, Luo SD, Wu SC, et al. Clinical Characteristics and Predictive Outcomes of Recurrent Nasopharyngeal Carcinoma-A Lingering Pitfall of the Long Latency. Cancers (Basel) 2022;14:3795. [Crossref] [PubMed]
52. Li JX, Lu TX, Huang Y, et al. Clinical characteristics of recurrent nasopharyngeal carcinoma in high-incidence area. ScientificWorldJournal 2012;2012:719754. [Crossref] [PubMed]