上消化呼吸道感染人類乳突瘤病毒種類分析之研究

Analysis of the Infection Types of Human Papillomavirus of the Upper Aerodigestive Tract

廖倩茹(Chien-Ji Liao)

指導教授 ： 周明智 ； 鄭雅文

中山醫學大學/醫學院/醫學研究所/碩士(2005年)

https://doi.org/10.6834/CSMU.2005.00075

摘要

人類乳突瘤病毒(HPV)與許多人類癌症有密切的關係。過去研究大多來自於子宮頸癌方面的研究，因為有極高比例的子宮頸癌患者有HPV的感染，尤其是高危險型之HPV16及18。HPV也與其他人類癌症有關，本研究室過去的研究結果亦發現，在肺癌病患之肺腫瘤組織中，HPV的感染有性別及抽菸習慣上的差異，不抽煙女性肺癌病患以HPV 16/18感染為主，而抽煙之男性肺癌患則與HPV 6/11較有關，因此推測不同性別和抽菸習慣之肺癌病患可能有不同型之HPV參與。為了了解其感染途徑，因此分析HPV6/11/16/18在上消化呼吸道的感染情形，除了可以了解HPV6/11/16/18與正常人上消化呼吸道之相關性，亦有助於了解HPV感染肺組織之可能途徑。
頭頸部惡性腫瘤病患佔台灣癌症死亡人數約5~6％，在衛生署92年的資料顯示，臺灣地區十大常見癌症死因排名中，口腔癌從過去排名在十名以外，大幅進昇為第七名，鼻咽癌也一直排在男性十大常見癌症死因的第十名。已知嚼檳榔、喝酒及吸菸是造成頭頸部惡性腫瘤的主要原因[1, 2]，還有一些像暴露在羊毛、木屑等環境因子也與頭頸部惡性腫瘤的發生有關。然而，仍有15~20%的頭頸部惡性腫瘤無法用以上原因解釋[3, 4]，因此推測可能有其他外來生物因子參與頭頸部惡性腫瘤的形成。從過去流行病學和分子生物學的文獻可知，人類乳突瘤病毒(HPV)可能參與了頭頸部惡性腫瘤的致病機轉[4-8]，其中又以HPV type-16與扁桃腺癌(tonsillar cancer)的研究最多[9-11]。此外，肺部和頭頸部在人體的解剖學上都有共通的上消化呼吸道UADT(upper aerodigestive tract) ，因此本研究共收集76位正常人的上消化呼吸道檢體與12位頭頸部惡性腫瘤病患的腫瘤檢體，以nested PCR分析檢體中HPV 6,11,16,18的感染率，結果發現76位正常人的上消化呼吸道檢體有30位HPV的感染，感染率為39.5%。12位頭頸部惡性腫瘤病患的腫瘤檢體有9位HPV的感染，感染率為75.0%。進一步分析其感染HPV的種類，發現這76位正常人之中，以HPV 6感染最多，共有19位，感染率為25% ( 19/76)；9位感染HPV的頭頸部惡性腫瘤病患，其感染種類也全都是HPV 6。
為了了解HPV在正常人上消化呼吸道的感染情形，同時做為HPV感染肺組織之可能途徑的參考，我們將76位正常人的上消化呼吸道檢體依照大體解剖部位區分為三個部分: 鼻腔(nasal cavity)、口腔(oral cavity)到咽部(pharynx)，觀察不同部位的感染情形。結果發現從鼻腔、口腔到咽部，都以感染HPV 6為最多，感染率分別為24.6%、25.0%、28.6%。若比較不同部位之易感性，發現以咽部(Pharynx)最容易受感染，平均感染率為85.7%，其HPV 6/11/16/18 的感染率分別為28.6%、14.3%、28.6%、14.3%。另外，同時想要了解是否頭頸部惡性腫瘤病患與非癌症控制組之間具有不同的吸煙習慣，結果發現12位頭頸部惡性腫瘤病患有9位吸煙 (75%)，76位非癌症控制組則有21位吸煙(27.6%)，表示頭頸部惡性腫瘤病患比正常人有較高之抽煙習慣。
由本研究之結果推測，不管在頭頸部惡性腫瘤病患或正常人之上消化呼吸道都與HPV 6有密切的關係，因此HPV 6不僅與頭頸部良性腫瘤有密切相關，也在頭頸部腫瘤癌化的過程中扮演著重要的角色，同時也提供HPV 6感染肺組織的可能途徑之證據。

關鍵字

人類乳突瘤病毒 ； 上消化呼吸道 ； 頭頸部惡性腫瘤

並列摘要

Human papillomaviruses are closely related to many cancers of human. The most known research was cervical cancer because of the high relationship between cervical cancer and HPV, especially the HPV 16/18. HPV is also related to other human cancers. Our previous reports have indicated the differences of gender and smoking habit in the carcinogenesis of lung cancers: non-smoking female lung cancer patients had higher infection rate for HPV 16/18, while the smoking male lung cancer patients had a higher rate of infection for HPV 6/11, suggesting that different types of HPV are involved in the carcinogenesis of lung cancers with the differences of gender and smoking habit. To know the infection route, thus the analysis of the infection types of HPV 6/11/16/18 in the UADT can not only elucidate its relationship with upper aerodigestive tract, but also tell us the possible route of HPV infection in lung cancers.
Head and neck cancers account for about 10% of death from all cancers in Taiwan , and according to the data of the ranks of cancer death from the Department of Health, Executive Yuan, Taiwan, between 1996 and 2002, oral carcinoma raised its rank from outside the 10th to the 5th , and nasopharyngeal carcinoma remained within the most 10 prevalent cancers . Betel nut chewing, smoking, and alcohol consumption are the main carcinogenic factors in head and cancers [1.2], other known risk factors include environment exposure to wool dust, wood dust and mineral fibres. There are , however, 15~20% of head and neck cancers that develop in the absence of exposure to the above-mentioned risk factors and of any obvious predisposing genetic defect [3,4], suggesting the presence of possible additional risk factors. Human papillomavirus (HPV) may be one of the promoting factors of head and neck carcinogenesis according to the epidemiological and molecular data [4-8], the most known one is the relationship between HPV type-16 and tonsillar cancers [9-11]. The head and neck shares the common upper aerodigestive tract (UADT) with the lung in anatomy, thus this study collected the specimens of the UADT of 12 head and neck cancers and 76 non-cancer individuals as the control group, and analyzed the infection types of HPV 6/11/16/18 by nested PCR. 30 of the 76 non-cancer individuals (39.5%) had HPV infection in their UADT tissues, and 9 of the 12 head and neck cancers (75.0%) had HPV infection in their tumor tissues. According to the infection types , 19 of the 76 normal individuals were type 6 , accounting for 25% (19/76) infection rate and all type 6 in the 9 head and neck cancer patients.
In order to analyze the infection rate of HPV in the UADT of normal individuals, and the possible routes of HPV infection in lungs , we divided the UADT of the 76 normal individuals into three different anatomical sites as nasal cavity, oral cavity, and pharynx, and studied the infection of HPV by the three different anatomical sites. The results showed that HPV 6 accounted for the most common type in all the three sites, the infection rates of HPV 6 were 24.6%, 25.0%, 28.6% for nasal cavity, oral cavity and pharynx respectively. As compared the predisposition of HPV infection by the three anatomical sites, the pharynx was the most predisposing site of infection, with 85.7% infection rate of all types , and 28.6%, 14.3%, 28.6%, 14.3% for HPV 6/11/16/18 respectively. On the other hand, the smoking habit was noted of 9 (75%) in the 12 head and neck cancer patients , and 21 (27.6%) in the 76 non-cancer control group individuals,and this indicated that head and neck cancer patients did have a higher rate of smoking habit.
According to the result of this study, the HPV type 6 was frequently associated with head and neck cancers and the normal UADT tissues , HPV 6 was related to the benign head and neck tumorigenesis . It also had some important role in head and neck carcinogenesis, and the study also provided some clues for the possible route of HPV 6 infection in lung tissues.

並列關鍵字

human papillomavirus ； upper aerodigestive tract ； head and neck cancer

參考文獻

61. Hsu YH, W.T., Horng IJ, Jan WC, Su IJ., Prevalence of human papilloma virus 16 or 18 in cervical cancer in Hualien, eastern Taiwan. Kaohsiung J Med Sci. 1997, 1997. 13(5): p. 315-9.

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