臺灣口腔和咽癌發生率趨勢分析- 歸類方式根據腫瘤原發部位及年齡-年代-世代分析

Abstract

背景 口腔和咽癌是主要的頭頸部惡性腫瘤，根據位置可分成口腔癌、鼻咽癌、口咽癌和下咽癌，這四類癌症的臨床特徵、治療方式、疾病預後互不相同。過去流行病學的研究，因特殊目的或受限於研究對象多寡，常見合併幾個部位的癌症為主題，卻鮮少有個別癌症的研究。本研究使用以全人口為基礎的臺灣癌症登記資料，主要目的是比較個別癌症的發生率趨勢和各自的年齡、年代、世代效應。 材料與方法 以臺灣癌症登記資料，取得西元1979到2008年間臺灣口腔和咽癌的個案，限制病理型態為鱗狀細胞癌或未分化癌，根據腫瘤原發部位採用ICD9四碼予以疾病歸類，計算口腔癌、鼻咽癌、口咽癌和下咽癌個別癌症不同性別的年齡標準化發生率、相對變化百分率、累計風險，以Joinpoint Regression Program比較各癌症的發生率趨勢，並以自我廻歸年齡-年代-世代模型分析臺灣男性口腔癌、鼻咽癌、口咽癌和下咽癌的發生率趨勢。 結果 臺灣口腔和咽癌以男性居多，男性以口腔癌發生率最高(24.74人/每十萬人, 2008年)，女性發生率最高則為鼻咽癌(2.54人/每十萬人, 2008年)。男性口腔癌、口咽癌和下咽癌的發生率趨勢是逐年增加，且男性口咽癌(6.51人/每十萬人, 2008年)、下咽癌(4.98人/每十萬人, 2008年)的發生率已逐漸逼近鼻咽癌(7.65人/每十萬人, 2008年)。鼻咽癌在男女性別間呈現不同的趨勢，男性鼻咽癌發生率趨勢為緩步上升，女性發生率則是緩步下降。此外，女性口腔癌發生率(2.07人/每十萬人, 2008年)也逐漸追上鼻咽癌的發生率(2.54人/每十萬人, 2008年)。 過去研究常用的ICD9三碼的疾病歸類方式和本研究採用ICD9四碼的疾病歸類相比較，前者會高估口腔癌的發生率和低估口咽癌的發生率。若研究未予以病理限制為鱗狀細胞癌或未分化癌，則男性鼻咽癌發生率趨勢將呈現不同的變化，為緩步下降。 將年齡、年代、世代三個效應分別取效應最強群組除以效應最弱群組，結果得到男性口腔癌、鼻咽癌、口咽癌、下咽癌年齡效應分別為7.96、3.35、17.09、60.45，年代效應分別為6.67、1.27、8.27、7.32，世代效應分別為2.08、1.19、1.63、1.99。 分析發現男性鼻咽癌的年齡-年代-世代模型效應明顯不同於口腔癌、口咽癌和下咽癌，而口腔癌、口咽癌和下咽癌彼此間有類似的年齡、年代、世代效應。 結論 鼻咽、口咽和下咽雖然構造相連，但是癌症發生率呈現兩種截然不同的表現，其原因可能是口咽、下咽和口腔有類似的致癌危險因子，和使用菸、酒、檳榔有關，而鼻咽癌則來自不同的致癌機轉，主要和遺傳、種族、EB病毒及環境因子相關。 根據腫瘤原發部位的ICD9四碼疾病歸類方式，和病理限制為鱗狀細胞癌或未分化癌的研究方式，可正確估計口腔和咽癌的發生率和趨勢，此方式值得後續研究者採用 和世界各國相比，臺灣男性口腔和咽癌的高發生率已名列前茅，而且男性口咽癌、下咽癌的發生率也逐漸追上鼻咽癌，從公共衛生、醫學研究和臨床診療三大觀點，將口腔癌、口咽癌、下咽癌和鼻咽癌個別分析研究，並建立防治計畫，實為臺灣當前重要的公共衛生議題。

Background and Objectives Cancers of the oral cavity and pharynx are common malignancy in the head and neck. According to location, they can be divided into cancers of the oral cavity, nasopharynx, oropharynx and hypopharynx. Each of them has different clinical feature, treatment and prognosis. And different sites of these cancers were usually combined in past epidemiological studies because of special purposes or limited case number in each group. Studies focused on individual cancer were less common before. Therefore, we conducted a population-based study here using the database from Taiwan Cancer Registry. The main objective of this study is to compare the incidence trend and the age, period, cohort effects for each of the four cancers. Materials and Methods Between 1979 and 2008, patients with cancers of the oral cavity and pharynx were enrolled from Taiwan Cancer Registry and classified according to the primary site of cancer by four digits of ICD-9. Only squamous cell carcinoma or undifferentiated carcinoma was included in this study. Gender-specific age-standardized incidence rate, percentage difference of incidence and cumulative risk were calculated for each cancer. The incidence trend of cancer was compared by the Joinpoint regression program. Then the individual cancer incidence of men between 1979 and 2008 was analyzed with autoregressive age-period-cohort model. Results In Taiwan, cancers of the oral cavity and pharynx had high incidence in men. As for the incidence in different gender, cancer of the oral cavity was highest in men and cancer of nasopharynx in women. Incidences of cancers of the oral cavity, oropharynx and hypopharynx in men continued to increase in recent three decades. And the incidence of cancer of the oropharynx or hypopharynx was close to that of the nasopharynx in men recently. Different incidence trend pattern happened in nasopharyngeal carcinoma between men and women. The incidence trend of nasopharyngeal carcinoma increased slowly in men but decreased slowly in women. Besides, the incidence of cancer of the oral cavity was rather close with that of the nasopharynx in women. The incidence of cancer of the oral cavity will be overestimated and that of cancer of the oropharynx will be underestimated, if cancer is classified by three digits of ICD-9 rather than by four digits of ICD-9. Besides, if the pathological restriction is not included in the study, the incidence trend of nasopharyngeal carcinoma in men will be changed completely which will decrease slowly. In age-period-cohort model, the relative risk of age effect for cancers of the oral cavity, nasopharynx, oropharynx and hypopharynx in men is 7.96, 3.35, 17.09 and 60.45 respectively. The relative risk of period effect for four cancers in men is 6.67, 1.27, 8.27 and 7.32 respectively. The relative risk of cohort effect for four cancers in men is 2.08, 1.19, 1.63 and 1.99 respectively. The result shows similar pattern of age-period-cohort model in cancers of the oral cavity, oropharynx and hypopharynx . Nevertheless, nasopharyngeal carcinoma has different pattern from those of other three cancers. Conclusions Though oropharynx is adjacent to nasopharynx and hypopharynx, the incidence trend is quite different among these three cancers. The reason is possibly that cancers of the oropharynx, hypopharynx and oral cavity have similar carcinogens including betel quid, tobacco and alcohol, whereas cancer of the nasopharynx is associated with inheritance, ethnicity, Epstein-Barr virus and environmental factors. Accurate estimation of the incidence and trend of cancers of the oral cavity and pharynx can be achieved by classification according to the primary site of cancer by four digits of ICD-9 and the pathological inclusion criteria only for squamous cell carcinoma or undifferentiated carcinoma. The methods and criteria of this study are good standards for the future study about this topic. In Taiwan, male has higher incidence of cancers of the oral cavity and pharynx than in the world. Besides, the incidence of cancer of the oropharynx or hypopharynx is getting close to that of the nasopharynx in men. From the viewpoint of public health, medical research and clinical medicine, it is important to study each of the four cancers individually to set up appropriate cancer prevention programs in Taiwan.