While the Indonesian government is currently developing a national population‐based cancer registry system, existing epidemiological data on NPC in Indonesia are derived exclusively from hospital-based medical record registries, and therefore may not represent the disease landscape in the country. An early report from 2012 described NPC as the fourth most common malignancy in Indonesia [19], and this was supported by a recently published imPACT Review coordinated by the Ministry of Health Indonesia [20]. Indonesia comprises more than one thousand ethnic groups across 38 provinces [21] and published data were predominantly originated from hospitals located at Western Indonesia, including Java and Sumatra. Studies conducted at Dr. Cipto Mangunkusumo National Hospital Jakarta showed that between 1996 and 2011, over 60% of NPC patients were of Javanese and Sundanese origin, whereas Chinese patients accounted for 10% or fewer of cases [19, 22]. These findings suggest that NPC incidence in Indonesia did not correspond closely to the demographic distribution of Chinese descendants, despite their large population in Jakarta and surrounding areas. Nevertheless, comprehensive national-level data are needed to draw definitive conclusions.

Late presentation remains a major challenge in NPC management, particularly in Indonesia. Reports from Yogyakarta (Dr. Sardjito General Hospital), Jakarta (Dr. Cipto Mangunkusumo National Hospital) and East Java (Dr. Soetomo General Hospital) indicated that 51%–70.5% of NPC patients presented with Stage IV disease [22–24]. Strikingly, findings from Dr. Kariadi General Hospital in Central Java indicated that 31.6% of patients diagnosed at an advanced stage presented with distant metastases (Stage IVC), highlighting the burden of late presentation [25]. NPC primarily affects adults of productive age, with incidence peaking between 40 and 59 [26]. Although a bimodal age distribution has been described in North Africa, showing a modest rise in incidence among those aged 10 to 25 [27], NPC is rarely seen among adolescents in Asia. Notably, in Jakarta, 20% of NPC patients (1,121 cases diagnosed between 1996 and 2005) were younger than 31 years, without evidence of a bimodal age distribution [19]. A subsequent study at the same hospital identified 49 NPC patients under 31 years of age, of whom 79.6% presented with Stage IV disease and 14% had distant metastases [28]. Similar trends were observed in an independent study from Dr. Zainoel Abidin General Hospital, Banda Aceh (2014–2019), where the mean age at diagnosis was 17.2 years, and most patients were diagnosed during late adolescence and early adulthood (53% aged 17–25 years; 47% aged 12–16 years) [29].

The prognosis for NPC patients in Indonesia is relatively poor. An early study in Yogyakarta reported a median survival of 21 months among 78 cases diagnosed between 2008 and 2011 [24]. A subsequent analysis involving a larger cohort of 759 patients diagnosed between 2007 and 2016 at the same hospital found a median observed survival of 31.08 months [30]. When extrapolated to a five-year period, the overall survival rate reached only 35%. Similar findings were reported in Jakarta, where a study showed a two-year overall survival rate of 39%–71% among young, non-metastatic patients [28]. Collectively, these results indicate that NPC survival outcomes in Indonesia were lower than those reported from neighbouring endemic Asian countries, where treatment with induction chemotherapy (IC) and radiotherapy yielded survival rates of 54.7%–83.2% during that period [31, 32]. Encouragingly, a more recent study from Central Java involving 50 patients diagnosed in 2018 reported a three-year overall survival rate of 60.8% following chemoradiation therapy [25]. However, no statistically significant difference in overall survival was observed between early- and advanced-stage patients in this study, a finding that contrasts with earlier studies from Yogyakarta and other Asian populations [30, 33, 34].

In Malaysia, NPC has ranked among the top ten most common cancers since the first Malaysian National Cancer Registry Report 2002 was published (https://nci.moh.gov.my/index.php/ms/main-menu-2/laporan), indicating that NPC is a major national public health issue. Malaysia is a multiethnic country comprising three main racial groups, namely Malay, Chinese and Indian, each with distinct social and cultural backgrounds. The genetic contribution to the pathogenesis of NPC in Malaysia is evident. Both Chinese males and females consistently show higher ASIRs than their Malay and Indian counterparts (Table 4). According to the Malaysian National Cancer Registry Report 2017–2021, the lifetime risks of developing NPC are 1 in 101 for Chinese, 1 in 344 for Malay and 1 in 1,233 for Indian [40]. Although a declining trend in ASIR has been observed among Chinese people over the past two decades, Malaysian Chinese males still demonstrate a higher ASIR (8.6 per 100,000 people) compared to males in China (3.4 per 100,000 people). Interestingly, an early report identified variations among Chinese subgroups, with Cantonese males showing the highest ASIR of 17.3, followed by the Hakka (Khek), while Hokkien and Teochew subgroups reported lower rates [35]. Previous studies have shown that Chinese migrants from southern China/Hong Kong to the United States retained a comparably high NPC incidence, but the risk decreased progressively across successive generation born in the United States [41]. The first generation of Malaysia Chinese was born in the 1900s, and even after more than a century of local residence, the persistently elevated ASIRs among this population suggest that environmental exposures may play an equally important role as genetic predisposition in determining NPC risk in Malaysia.

Regional disparities significantly influence the burden of NPC in Malaysia. Notably, the two states located on the island of Borneo, Sarawak and Sabah, recorded the highest ASIRs of NPC among all 13 Malaysian states [42]. The populations of Sarawak and Sabah comprise a multitude of ethnic groups, with indigenous peoples accounting for approximately 60%–70% of the total population. A landmark study published in 2004 reported that between 1996 and 1998, the Bidayuh, a native group in Sarawak, exhibited the highest ASIRs globally, reaching 31.5 in males and 11.8 in females [3]. The elevated incidence among the Bidayuh has persisted over time; a more recent analysis of 3643 NPC cases in Sarawak (1996–2015) found ASIRs of 27.8 in males and 11.6 in females [43]. These data are comparable to those reported in high-incidence regions of southern China, such as Zhongshan and Zhuhai regions, where ASIRs were approximately 25 for males and 9 for females [44]. In neighbouring Sabah, elevated NPC incidence rate has similarly been observed among indigenous populations, particularly the Dusun and Kadazan groups, although their ASIRs were lower than those reported in Bidayuh [39, 45, 46].

Consistent with global trends, Malaysia demonstrates a predominant pattern of late-stage NPC diagnosis. A multi-institutional prospective study conducted between July 2007 and February 2008 reported that 47% of new NPC cases were diagnosed at Stage IV [47]. Sadly, this challenge persisted over time. Even after more than a decade, 46.7% of NPC cases remained at Stage IV at initial presentation, according to the Malaysian National Cancer Registry Report 2017–2021. Although juvenile NPC is less common in Malaysia than in Indonesia, it has been documented among the Kadazan, the indigenous people of Sabah, in several early studies [45, 46, 48]. The first report on NPC incidence in Sabah, published only in 2021, did not provide age-specific demographic data [39]. Therefore, further study is warranted to evaluate the prevalence of juvenile NPC in Malaysia.

Existing publications on NPC survival outcomes in Malaysia are relatively dated. The unavailability of intensity-modulated radiotherapy (IMRT) facilities in public hospitals (Penang General Hospital and Hospital Kuala Lumpur) and academic medical centres (University Malaya Medical Centre and Hospital Universiti Sains Malaysia) was associated with unsatisfactorily low 5-year overall survival (OS) of 33.3%–38% for patients treated between 1998 and 2007 [49, 50]. Subsequent studies involving patients treated between 2002 and 2008 reported an improvement in OS to 51.6%–58.6%, largely attributed to the increased adoption of concurrent chemoradiotherapy (CCRT) [51, 52]. Nevertheless, these outcomes remained inferior to those achieved with IMRT-based treatment, where 5-year OS rates exceeding 80% have been reported in developed centres [53]. Consistent with this, a private medical centre in Malaysia, where IMRT is the standard of care, reported a respectable higher 5-year OS of 73% [54]. IMRT-based treatment has only been implemented in Malaysian public hospitals since 2011 [55], and outcome analyses from major cancer centres are eagerly awaited.

Singapore is a compact nation characterized by its highly urbanized setting. The Singapore Cancer Registry, established in 1967, monitors population-based cancer trends and patterns across the country. In the most recent Singapore Cancer Registry Report 2018–2022, NPC is not listed among the ten most common cancers overall [56]. However, it remains clinically relevant; NPC ranks 10th in cancer-related mortality among men, and is the third most common cancer in males aged 30–49 years. In the younger population (0–29 years), NPC also appeared as the 10th most common cancer, with 22 cases recorded during the reporting period. As young-onset NPC is rare, particularly in urban settings, it would be valuable to investigate whether its occurrence in Singapore reflects underlying genetic susceptibility or lifestyle changing, such as increasing alcohol consumption.

The ethnic makeup of Singapore closely mirrors that of Malaysia, comprising three main groups, namely Chinese, Malay and Indian. Unlike Malaysia where Malay accounts for more than 70% of the population, Singapore is predominantly Chinese (approximately 74%). Consistent with demographic patterns of Chinese ancestry, the ASIR of NPC is highest among Chinese, intermediate among Malays, and lowest among Indians [57]. Earlier analyses have also reported variation within Chinese subgroups; major dialect groups (Hokkien, Teochew, Cantonese, Hainanese, Hakka) all showed elevated risk, with Cantonese people exhibiting particularly high susceptibility [58]. A secular trend analysis covering 1973–1997 reported a significant decline in NPC incidence, especially among cohorts born after 1958 [59], suggesting environmental and lifestyle changes might have contributed to the reduction of NPC over time.

Across many SEA countries, close to 50% of NPC patients present with Stage IV disease. In contrast, the proportion appears lower in Singapore. At the National University Hospital (NUH) Singapore, 35.5% of patients treated between 2002 and 2012 were diagnosed at Stage IV [60]. Similar findings have been reported at the National Cancer Centre Singapore (NCCS), where 30% of patients treated between 2002 and 2005 and 32.6% treated between 2017 and 2023 presented with Stage IV disease [61, 62]. Notably, the latter study reported no cases of Stage IVc at diagnosis. A dedicated epidemiological investigation would help determine whether this represents a genuine downward trend and whether improved awareness was driven by higher education levels. When comparing ethnic groups, non-Chinese patients (Malay, Indian, Caucasian, Kenyan and others) were more likely to present with advanced nodal disease, although their OS did not differ significantly from Chinese patients [60].

Singapore is classified as a country with a very high HDI. Early-stage disease (stage I/II) is treated with radiotherapy (RT) alone or CCRT, while stage III/IV disease is treated with either CCRT or IC followed by CCRT, with or without adjuvant therapy [61]. IMRT has been used at NCCS since 2002, and a cohort of 195 IMRT-treated patients (2002–2005) demonstrated an impressive 3-year overall survival of 94.3% [62], comparable to other international centres. IMRT also became the standard radiotherapy modality at the NUH in 2006 [60]. Taken together, Singapore demonstrates some of the strongest NPC management outcomes in SEA, largely attributable to its high socioeconomic development and strong healthcare infrastructure, resulting in superior survival outcomes for NPC patients.

Published data on the incidence of NPC in Vietnam are quite limited but the epidemiological pattern of NPC in Vietnam appears to mirror that of other SEA countries. The first cancer registry in Vietnam was established in 1988 in Hanoi followed by a registry in Ho Chi Minh City (HCMC) in 1990. Other regional registries have subsequently been set up, but most available data come from Hanoi and HCMC, which have been reported to generate the best quality data in the country [63]. Data from these registries is used by The GLOBOCAN to model national cancer statistics and the most recent estimate indicates that NPC is the 9^th most common cancer in Vietnam and the 7^th highest cause of cancer mortality [1]. In Vietnam, local data indicate that NPC was the 5^th most common cancer in males between 2000 and 2018 [63].

Data from a number of studies demonstrates that NPC in Vietnam exhibits similar characteristics as those in other SEA countries, including age, gender and histological subtypes [64]. As in other SEA countries, patients appear to present with late-stage disease, but the data are limited. In a small single-centre study in Hanoi of 31 patients, 67.74% of patients presented with late-stage disease (stage III-IV), where 38.71% accompanied by tissue invasion and distant metastasis [65]. In a more comprehensive study of 8974 cases of head and neck cancers, NPC contributed the highest proportion of stage IV cases (14.53%) among these tumours [64], supporting the overall premise that NPC is often diagnosed at late stages. There is some evidence to indicate a geographical variation within Vietnam. Data from the Hanoi and HCMC cancer registries in 2000 indicated that NPC was more frequently observed in Hanoi (ASIR of 10.7 in males, 5.1 in females) than in HCMC (ASIR of 5.1 in males, 1.5 in females) [66], but this requires confirmation.

Published data on prognosis and survival outcomes in Vietnam remain limited. In a recent cohort of patients with advanced-stage (III/IVA) undifferentiated NPC treated at the Vietnam National Cancer Hospital (2021–2024), 96.6% received IC followed by CCRT. IMRT was administered to 70.7% of patients, and 77.5% achieved disease-free survival beyond 12 months [67]. These findings highlight the need for more comprehensive epidemiological and clinical studies to better characterise the NPC landscape in Vietnam.

To date, only one study has assessed the incidence of NPC in Philippines. The country has two recognised population-based cancer registries, namely the Philippine Cancer Society-Manila Cancer Registry (PCS-MCR) and the Department of Health-Rizal Cancer Registry (DOH-RCR), which cover Metropolitan Manila and the nearby Rizal Province. In collaboration with the World Health Organisation International Agency for Research on Cancer (WHO IARC), these registries have made significant contributions to cancer data collection in the Philippines. Between 1980 and 2007, data from these registries consistently ranked NPC among the top 10 cancers in Filipino males [68]. However, these sources do not comprehensively represent all regions of the Philippines. In recognition of this limitation, a multicentre study was conducted across four major oncology centres in different cities, University of Santo Tomas (Manila), Makati Medical Centre (Makati), Philippine Oncology Centre Corporation (Quezon), and Cardinal Santos Memorial Medical Centre (San Juan), to collect demographic data on NPC patients [69]. Although the sample size was small (49 NPC patients), the study provided insights not captured by the IARC reports. Particularly, it showed that approximately one-third of cases originated from the northern and central Luzon provinces (Manila is at the southern Luzon), with incidence increasing with age and peaking at 50–59 years. Consistent with trends in other SEA countries, 44.9% of cases were diagnosed at Stage IV [69]. This study also highlighted that NPC incidence in the Philippines may have been underreported.

Thailand currently has 16 population-based regional cancer registries that collectively provide national coverage across different regions. In collaboration with these registries, National Cancer Institute of Thailand publishes the Cancer in Thailand monograph, a series of comprehensive statistical reports on cancer incidence and epidemiology. Although NPC is not listed among the ten most common in Thailand in the latest monograph 2019–2021 [70], it ranks 7^th among cancers in men according to the 2023 hospital-based cancer registry [71]. While the ASIR of NPC in Thailand (2.2 per 100,000 people) is considerably lower than in neighbouring SEA countries, the country still ranks 6^th worldwide in NPC incidence [1]. These data underscore that NPC remains an important cancer in Thailand. The comparable ASIRs across all regions indicate no significant geographical disparity within the country [70].

NPC is well recognised to be predominantly of the non-keratinising subtype in endemic regions [72]. An analysis of 1990–2014 data from four Thai registries (Chiang Mai, Khon Kaen, Songkhla, and Lampang) provided additional insight [73]. Non-keratinising subtype constituted 66%–79% of cases in Chiang Mai, Khon Kaen, and Lampang. In contrast, in Songkhla (located at the southern Thailand), the keratinising subtype accounted for approximately 60% of cases, and the authors attributed to historically high smoking prevalence in the region. Nonetheless, the incidence of keratinising NPC has significantly declined over time and non-keratinising NPC now represents the predominant subtype in Thailand [74, 75].

Although comprehensive, the Cancer in Thailand monograph does not include information on disease staging. Evidence from independent studies, however, indicates that late-stage presentation is also common in Thailand [74, 75]. Between 2008 and 2020, 43%–45% of NPC patients treated in hospitals in Bangkok and Songkla presented with Stage IV disease. A multicentre study involving four major Thai cancer centres (Ramathibodi and Siriraj Hospitals at Mahidol University, King Chulalongkorn Memorial Hospital and Songklanagarind Hospital) reported that CCRT was the predominant treatment modality from 2008 to 2020, with a 5-year OS rate of 62% [75]. The widespread adoption of IMRT and volumetric modulated arc therapy (VMAT), supported by national health coverage since 2007, has contributed to significant improvements in survival and reductions in treatment-related toxicities. Patients treated with IMRT/VMAT achieved a 5-year OS of 76%, compared with 51% for 2D techniques and 58% for 3D conformal radiotherapy.

NPC frequently presents at an advanced stage, largely due to its hidden anatomical location and the non-specific nature of early symptoms (such as nasal congestion or discharge), which are often overlooked or misattributed to benign conditions [102]. Most patients seek medical attention only when visible neck lumps appear, making this the most common presenting symptom [103]. This delay is particularly relevant for patients in rural areas, where educational levels and socioeconomic status are generally low. A Malaysian study found that 41.5% of rural respondents had limited health literacy [104]. In Sarawak Malaysia, a study involving 216 patients reported a mean delay of 176 days from symptom onset to seeking professional attention [105]. The primary reasons identified were lack of awareness of NPC and its seriousness (72%), absence of pain (30%) and initial reliance on traditional treatment (24%). A similar pattern was observed in Indonesia, where a majority of the patients experienced unilateral ear problem (the earliest sign of NPC) several months before presenting with cervical lymph node enlargement (a sign of late stage NPC) [19]. In the Philippines, the average duration of symptoms before first consultation was 18.3 months, with 78% (28 of 36) of patients had symptoms more than 3 months at presentation [106]. Beyond limited awareness, cultural reliance on traditional medicine further delays diagnosis and treatment. Some patients abandon standard treatment mid-course in favour of alternative medicine, which are often unregulated and lack scientific validation [91]. Denial of diagnosis also contributes to treatment delays.

Early detection of NPC is often hindered by its symptom overlap with common upper respiratory infections, leading to misdiagnosis by general practitioners (GPs) and thereby a delay in referral. A study in Yogyakarta Indonesia revealed that knowledge on NPC of GPs working in the Primary Healthcare Centres was insufficient, with many of them were unaware of NPC prevalence in their region [107]. This knowledge gap stems from insufficient training during medical education and limited knowledge in clinical practice. Similarly in Kuala Lumpur Malaysia, an early study revealed delayed diagnosis was attributed to poor awareness among primary healthcare workers, with a median diagnostic delay of 127 days [108]. Furthermore, NPC symptoms such as blurred vision and diplopia may prompt patients to consult ophthalmologists, underscoring the need for broader awareness among various medical specialties [106]. Enhancing education and training for regional healthcare providers is a critical first step for timely diagnosis and intervention.

Treatment delays also arise from prolonged overall treatment time (OTT) in SEA countries. Interruptions in radiotherapy causing a prolonged OTT have been reported to be detrimental for local disease control and survival outcomes of NPC [109]. An early study in Kuala Lumpur Malaysia showed that only 72.2% of patients completed their treatment within the recommended OTT [52]. This issue was further well-documented in a study in Yogyakarta Indonesia involving 68 patients between 2011 and 2012 [110]. The results showed that limited radiotherapy units led to treatment delay of 3–4 months and extended OTT by 10–12 days, significantly affecting treatment outcomes. In part this issue is often caused by equipment downtime due to poor maintenance or aging infrastructure. While urban centres may have addressed these challenges, they likely persist in rural areas across SEA.

Access to healthcare facilities remains a major barrier to the timely diagnosis and treatment of NPC in SEA, particularly in rural and remote regions [73, 91]. Geographic isolation, inadequate infrastructure, and limited transportation options significantly hinder patients from reaching appropriate medical services. In many rural areas, hospitals or oncology centres are located far from communities, requiring patients to travel over long distances. For example, in Sarawak Malaysia, patients from interior regions must rely on logging roads or rivers to reach tertiary hospitals, creating substantial delays and discouraging treatment-seeking behaviour [111]. Similar challenges are reported in Indonesia, where rural patients frequently struggling with the absence of reliable public transport and long travel times to urban medical centres [112]. Beyond the direct costs of treatment, the urban-centric distribution of healthcare providers compels rural patients to incur additional costs for travel, accommodation, and caregiving. These financial and logistical burdens often lead to delays in seeking care or, in some cases, abandoning treatment altogether. Although this issue has not been specifically documented in the literature as directly influencing NPC outcomes in SEA, it has been implied in a study from Thailand [73]. Northern Thailand encapsulates a “hill tribe” population; incidentally, registries from Chiang Mai and Lampang (north) reported poorer survival outcomes compared with those from Khon Kaen (northeast) and Songkhla (south). Given that limited access to healthcare is a well-recognised challenge across many developing countries, it is highly plausible that NPC patients in SEA experience similar barriers.