高危型HPV-18感染可增加口腔癌患者患上第二恶性口腔肿瘤的机会

　　根据台湾的研究结果，约三分之一的口腔鳞状细胞癌（OSCC）的病人由人类乳头状瘤病毒（HPV）感染导致，而其中高危HPV感染为四分之三左右。同时研究表明，HPV变种HPV-18的感染较其他未变异的同属病毒更能有效的导致病人继发性的恶性肿瘤的发生。

　　研究者同时指出，因为病人纳入数量有限，研究结果仍需要大样本的研究去进一步明确。然而，对于“高危HPV-18的感染在继发性恶性肿瘤的发生中产生重要的作用”的研究结论，他们补充说目前还仅适用于口腔疾病。Ann-Joy Cheng（长庚大学，桃源县，台湾）及同事调查了103个平均年龄49岁、感染HPV病毒的早期口腔癌手术病人。研究者从参与的病人肿瘤组织中识别得到38种类型的HPV病毒，并且发现30.1%的病人至少存在一种类型的病毒感染阳性。事实上，最常见感染的病毒亚型为HPV16及HPV18，分别占51.6%、22.6%的比例，他们均被认为是致癌的高危因素。陈及合作者发现研究中的33.3%舌癌患者及22.7%颊癌患者为HPV阳性，但HPV阳性患者在性别、肿瘤位置、肿瘤分期及肿瘤细胞分化程度无统计学差异。另外，对于存在OSCC的明确危险因素如吸烟、饮酒、嚼食槟榔等患者，HPV的感染率并未见显著提高。陈等认为，OSCC的发病是由HPV感染及其他致癌因素共同引起。在中位数为41个月的术后随访中，总共12个病人出现包括软腭癌、口底癌、下龈癌及食道癌在内的第二原发肿瘤。虽然HPV的感染同第二原发肿瘤的发病无相关性，但是进一步研究发现却同HPV18的感染具有相关性。在感染HPV-18的7个患者中，其中的3个患者发展成为第二原发肿瘤。同时研究者指出，继发性肿瘤组织出现了同样的HPV亚型病毒。

　　作者强调，研究结果支持区域性癌变的理论，这一理论认为第一及第二原发肿瘤的发生常常具有相同的病因。

原始出处：

Huang SF, Li HF, Liao CT, Wang HM, Chen IH, Chang JC, Chen YJ, Cheng AJ. Association of HPV infections with second primary tumors in early-staged oral cavity cancer. Oral Dis. 2012 May 25. doi: 10.1111/j.1601-0825.2012.01950.x.

Objective:  The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain. Materials and Methods:  The study recruited 103 patients with pathological early-stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV-genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi-square, Kaplan-Meier, and logrank tests. Results:  Thirty-one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease-free survival or overall survival). However, infection with HPV-18 was associated with the occurrence of a second primary cancers (P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy. Conclusions:  There are 30% of the patients with OSCC infected with HPV, with most high-risk types. HPV-18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result.