作者: 奇譽 劉耿僚 醫師
頭頸部癌症(head and neck cancers)病患佔台灣癌症死亡人數約5~6％，且95%以上為扁平細胞癌(squamous cell carcinomas of head and neck , HNSCCs)。其中口腔癌從過去排名在十名以外，大幅進昇為第五名，更位於男性癌症中的第四名。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。但仍有10~20%的頭頸部惡性腫瘤無法用常見的原因解釋，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誘發與形成。從過去的文獻可知，人類乳突瘤病毒(human papillomavirus, HPV)與許多人類癌症有密切的關係。其中研究最多的是子宮頸癌方面，尤其是高危險型之HPV type 16及18。至於其與頭頸部惡性腫瘤的關係則仍不清楚，至今未有定論。本研究先收集76位非癌症正常上消化呼吸道(upper aerodigestive tract；UADT)黏膜檢體及23位頭頸癌患者血液，利用巢疊式聚合酶連鎖反應(nested PCR)與real-time quantitative PCR分別分析高危險型HPV 16與18的感染情形，結果發現76位非癌症組的上消化呼吸道黏膜檢體有4位HPV 16或18的感染，感染率為5.3%。而本實驗室先前的研究顯示非癌症黏膜中較常見的低危險型HPV 6/11感染率可達32.9%，可見高危險型的HPV 16/18在正常上消化呼吸道黏膜中並不多見(32.9% vs 5.3%)。而在23位頭頸癌患者血液中以real-time quantitative PCR分析血液中HPV 16/18的DNA copy numbers，結果有7位HPV 16陽性(30.4%)，其平均copy number為26505.58±7525.01/μg DNA，8位HPV 18陽性(34.8%)，其平均copy number 為2586.86±368.0/μg DNA。分析其臨床相關性發現HPV與腫瘤期別有關，癌症早期者血液中病毒感染率較高，且病毒DNA拷貝數也較高，而晚期者較低。HPV在極具局部侵犯性或遠處轉移能力的頭頸癌中較少見，而且HPV的感染率在患有糖尿病的癌症患者中較高。因此推論，如果HPV是頭頸癌的致癌因子之一，則其可能是在頭頸癌發生過程的早期介入，並形成一類不同於由傳統致癌因子起始的頭頸癌。
Head and neck cancers account for about 5~6% of death from all cancers in Taiwan , and 95% of them are squamous cell carcinomas ( HNSCCs). Oral cancers , one subset of head and cancers raised its rank of annual death of cancers from outside the 10th to the 5th , and to the 4th in men. Betel quid chewing, tobacco smoking and alcohol intake are well-known risk factors in the aetiology of HNSCCs. There are , however, 10~20% of HNSCCs that occur in the absence of exposure to the well-known risk factors , suggesting the presence of possible additional biological risk factors. Human papillomavirus (HPV) is involved closely in many of human cancers reported by the literature. Its relationship with the uterine cervical cancers has been well documented , especially the high-risk HPV type 16 and 18, but it is still unclear about its role in the HNSCCs. In this study we collected the mucosa of 76 non-cancerous normal upper aerodigestive tract (UADT) and the blood of 23 patients with head and neck cancers, and analyzed the infection status of the high-risk HPV 16/18 by nested PCR and real-time quantitative PCR respectively. There were 4 cases of HPV 16/18 infection in the 76 specimens of non-cancerous normal UADT mucosa, with infection rate of 5.3%. It implied that it was relatively rare of high-risk HPV infection in the normal UADT while compared with our previous reported 32.9% infection rate of low-risk HPV 6/11. Then we quantified the DNA copy numbers of HPV 16/18 in the blood of the 23 patients with head and neck cancers by real-time quantitative PCR. There were 7 cases of positive HPV 16 (30.4%) with a mean value of 265055.76±7525.01 copy numbers per μg DNA, and 8 cases of positive HPV 18 (34.8%) with a mean value of 2586.86±368.0/μg DNA. The analysis with clinical parameters showed that HPV infection was related to the earlier stage of head and neck cancers, but less in the late stages and those with aggressive and distant metastatic tumors. The significant higher infection rate of HPV in the cancer patients with diabetes mellitus compared with those cancer patients without diabetes mellitus was also noted. So we concluded that HPV might involve in the early stage of the tumor transformation and represent one special subset of the HNSCCs that was different from those initiated by the
traditional well-known carcinogenic risk factors if HPV was definitely one of the
carcinogenic factors.
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