Incidence trend of nasopharyngeal carcinoma from 1987 to 2011 in Sihui County, Guangdong Province, South China: an age-period-cohort analysis

Nasopharyngeal carcinoma (NPC) is a malignant tumor arising from the epithelial cells that cover the surface and line of the nasopharynx. According to the International Agency for Research on Cancer, NPC is rare in most parts of the world, with an incidence of <1/100,000 person-years for both males and females; however, it is a prevalent malignancy in the Cantonese population in South China (including Hong Kong), with an incidence of >20/100,000 in endemic areas [1]. The incidence varies appreciably in different areas of China; the highest risk areas are in South China, especially in Guangdong Province, whereas low rates are generally observed in North China [2,3]. NPC is more predominant in males, with a male-to-female ratio of >2:1 in most populations [4]. Through much extensive research into the etiology of NPC, epidemiologic evidence suggests that Epstein-Barr virus (EBV) infection and genetic susceptibility are important etiologic factors for the disease [5]. Furthermore, diet and environmental factors might also play significant roles in the pathogenesis of NPC, including the consumption of salted fish and other preserved foods that contain nitrosamines, mutagens, and EBV-reactivating substances [6-9], occupational exposure to formaldehyde [6], and cigarette smoking [10,11].

Primary preventative measures against NPC are difficult because the underlying mechanisms of its development are unclear; therefore, screening, as a secondary preventative measure, is the most effective way by which to prevent NPC in endemic areas. Since 1986, several large-scale, population-based screening programs for NPC have been conducted in Sihui County, Guangdong Province, China using EBV-related antibodies as screening markers [12,13]; however, the effect of screening on the incidence and mortality of the disease has not yet been reported.

In the past several decades, declining incidences of NPC have been observed in Chinese populations in Hong Kong, Taiwan, Los Angeles, and Singapore [14-16]. Some important lifestyle factors such as decreased consumption of salted fish and preserved food and increased westernization of dietary habits might be responsible for the observed decrease in incidence; however, the incidence in South China remained stable [2,17,18]. A previous study indicated that the incidence of NPC in Sihui County remained stable until 2002 [17], but whether age, diagnosis period, and birth cohort affect the incidence of NPC remains unknown.

The purpose of our study was to the determine the secular trend of NPC and to explore the potential effects of age, diagnosis period, and birth cohort on the incidence changes of NPC from 1987 to 2011 in Sihui County, South China.

The present study demonstrated that the secular trend of NPC incidence remained stable with only slight fluctuation in Sihui County from 1987 to 2011. A similar incidence trend was observed in other regions of Guangdong and Guangxi Provinces, China [2,17]; however, the incidence of NPC has declined steadily in Hong Kong and Taiwan over recent decades [14,24]. The migrant epidemiologic studies conducted in Chinese populations in Singapore, Hong Kong, and Los Angeles showed a rapid reduction in NPC incidence from 1973 to 1997 in both males and females. In Singapore, the incidence of NPC in Chinese populations dropped from 1993 to 1997 in both sexes [15]. The phenomenon of heterogeneous secular trends of NPC incidence among different areas and populations might be partially explained by the diversity of environmental risk factors in different areas.

Some important lifestyle factors for NPC, such as the consumption of salted fish and preserved food and were expected to decrease as environmental changes and the westernization of dietary habits became more prevalent. This is presumed to be the reason for the decline in NPC incidence in Hong Kong and Taiwan [14,24]. During recent decades, with the rapid upward trend in the economy of Sihui County, changing lifestyles, dietary habits, and living conditions were also remarkable; however, we observed that the secular trend in NPC incidence remained stable until 2011. This coincided with the findings of other researchers [2,17,18]. We presumed that this trend might be because the effects of the changes in environmental factors lag behind the incidence of NPC or because some unknown environmental factors still exist in South China.

Our Joinpoint regression data suggested that the incidence of NPC increased from 1987 to 1999 for females and from 1987 to 1996 for males. Another significant increase for males appeared in 2003–2009, but each increase was followed by a decrease. These fluctuations within different periods are partly because of the two population-based NPC screening programs conducted in Sihui County: the first recruited participants from four towns in 1987, 1992 until 1997 [12]; the second was an ongoing screening project, of which the first round was conducted in six towns from 2008 to 2009 [13]. More early-stage NPC cases were detected, which indicated that the incidence increased during the screening period.

The age effect reflects physiologic differences among different age groups in the susceptibility to a given disease. In the present study, we found that the risk of NPC increased with age until 55-59 years and decreased thereafter; this finding was consistent with data from previous studies in endemic areas [25]. The period effect usually reflects the roles of multiple factors on the given disease that equally affect all age groups during a period of time. In our study, the introduction of new diagnostic techniques, changes in environmental factors, and modulation of lifestyles together might result in the unchanged effect by period. The birth cohort effect on NPC might result from different environmental exposure levels in different birth cohorts. The effect of lifestyle factors, which might be fixed early in life, is most likely reflected by the cohort effect [24]. Birth cohort-stratified incidences in males and females showed two trends. In males, the cohort effect is curved, with NPC risks increasing from the earliest cohorts, peaking in the 1957 cohort, and decreasing in younger cohorts from the 1957 cohort to the 1972 cohort; however, the RRs increased with undulation in the 1972 cohort of females. We presumed that the increased NPC risk in the younger female cohort might be due to increased cigarette smoking. A meta-analysis reported that cigarette smoking increased the risk of NPC [11]. Evidence from several studies conducted in Guangdong Province showed that the smoking rate was higher in males than in females but the smoking rate in males has decreased, whereas that in females has increased in recent years [26,27]. Moreover, exposure to secondhand smoke was more prevalent in females than in males [26,27].

There are several limitations that must be considered when interpreting the results from this study. With respect to the statistical methods, when using the APC model analysis, the sample size appeared too small to achieve robust estimates; thus, the age, diagnosis period, and birth cohort effects should be interpreted with caution. In addition, our study lacked adequate data to determine the incidence trend by histological subtype because the detailed histological subtype data for each cancer case were not included on the cancer report card in Sihui County. In the future, it might be better to analyze the incidence trend by different histological subtypes of NPC if the relevant data can be collected.

In conclusion, the incidence trends for NPC remained generally stable in Sihui County from 1987 to 2011, with an increase during 2003–2009. The RRs of NPC in younger female birth cohorts increased; the underlying reasons for this will be further explored. Because NPC remains a significant health burden in Sihui County, it is worthwhile to conduct epidemiologic studies on genetic susceptibility, environmental factors, and their interactions.