北京大学学报(医学版) ›› 2016, Vol. 48 ›› Issue (1): 84-88. doi: 10.3969/j.issn.1671-167X.2016.01.015

• 论著 • 上一篇    下一篇

白斑、扁平苔藓及口腔癌中人类乳头瘤病毒的检测

曹婕1, 金建秋2, 邓大君3, 刘宏伟4△   

  1. (1. 北京大学口腔医学院·口腔医院第二门诊部,北京100101;2.北京医院口腔科,北京100730;3. 北京大学肿瘤医院暨北京市肿瘤防治研究所病因研究室,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142;4. 北京大学口腔医学院·口腔医院黏膜科,北京100081)
  • 出版日期:2016-02-18 发布日期:2016-02-18
  • 通讯作者: 刘宏伟 E-mail: hongweil@126.com
  • 基金资助:

    北京市科技计划课题(Z090507017709016)资助

Determination of human papillomavirus in oral leukoplakia,oral lichen planus and oral squamous cell carcinoma

CAO Jie1, JIN Jian-qiu2, DENG Da-jun3, LIU Hong-wei4△   

  1. (1.Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing 100101, China; 2.Department of Dentistry, Beijing Hospital, Beijing 100730, China; 3.Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education; Department of Etiology, Peking University Cancer Hospital & Institute, Beijing 100142, China; 4.Department of Oral Medicine and Traditional Chinese Medicine, Peking University School and Hospital of Stomatology, Beijing 100081, China)
  • Online:2016-02-18 Published:2016-02-18
  • Contact: LIU Hong-wei E-mail: hongweil@126.com
  • Supported by:

    Supported by Beijing Municipal Science And Technology Project(Z090507017709016)

摘要:

目的:比较口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)发展过程中各阶段病损的人类乳头瘤病毒(human papilloma virus, HPV)感染率,以探讨将HPV感染作为癌变预测信号的可能性,同时比较两种方法在检测口腔内HPV感染方面的灵敏度差异。方法:使用第二代杂交捕获(hybrid capture,HC-Ⅱ)法检测255例口腔黏膜上皮细胞样本中的HPV感染情况,样本取自12例健康口腔黏膜、211例病理诊断的病例和32例临床诊断的病例,具有病理诊断和临床诊断的病例包括口腔黏膜良性病变8例、癌前病变口腔黏膜白斑(oral leukoplakia,OLK)伴上皮单纯增生74例、OLK伴上皮异常增生(oral epithelial dysplasia, OED)42例、癌前状态扁平苔癣(oral lichen planus,OLP)91例以及OSCC 28例。使用原位杂交(in situ hybridization,ISH)法检测109例石蜡包埋组织中的HPV感染情况,包括33例OSCC 和76例OLK,76例OLK中有30例上皮单纯增生、15例轻度OED、15例中度OED、16例重度OED。结果:OLP样本的HPV阳性率为12.12%(8/66),高于OLK (2.59%, 3/116, χ2=4.666,P =0.031)及OSCC(7.14%, 2/28, χ2=0.513,P=0.474);OSCC样本的HPV阳性率(7.14%,2/28)高于OLK(2.59%, 3/116),但差异无统计学意义;烟斑样本只有1例,没有参与统计学分析。ISH法检测109例口腔黏膜病损石蜡切片中16/18型及31/33型HPV DNA,仅1例OSCC样本为阳性;同时经HCⅡ和ISH法检测的样本中有94.6%(35/37)的检测结果一致,均为阴性;另2例分别为OSCC早期浸润和OLK伴上皮单纯增生,经HC-Ⅱ检测为HPV阳性,但ISH检测结果为阴性。随访66例参与HPV检测的OLP患者,平均随访期为(36.2±10.5)个月,发现其中3人发生了癌变,HPV阳性患者癌变率为12.50%(1/8),高于HPV阴性患者癌变率3.45%(2/58),通过卡方检验差异无统计学意义,P=0.249。结论:没有足够证据证明HPV感染或检测阳性可作为预测OLK癌变的信号;患OLP的患者处于癌前状态,OLP中HPV检出率高于OLK及OSCC,提示OLP患者由于某种原因对HPV易感,可考虑为OLP 患者常规做HPV检测,推荐使用HC-Ⅱ法,同时应对HPV阳性的OLP患者加强随访。

关键词: 乳头瘤状病毒科, DNA, 病毒, 口腔白斑, 扁平苔癣, 口腔, 口腔肿瘤

Abstract:

Objective: To investigate the possibility for human papillomavirus (HPV) infection to be a predictable signal for the carcinogenesis of oral mucosa by comparing the prevalences of HPV in each stage of oral mucosal carcinogenesis and to compare the sensitivity differences of the two methods in detecting HPV infection in oral cavity.  Methods:The hybrid capture (HC-Ⅱ) was used to detect infection of HPV in 255 samples taken from 12 cases of healthy oral mucosa, 211 cases of patients with pathological diagnosis and 32 cases of patients with clinical diagnosis. The diagnosed cases included 8 cases of benign lesions of the oral mucosa, precancerous lesions [74 cases of oral leukoplakia (OLK) with hyperplasia and 42 cases of OLK with oral epithelial dysplasia (OED)], 91 cases of precancerous condition [oral lichen planus (OLP)] and 28 cases of oral squamous cell carcinoma (OSCC). And in situ hybri-dization (ISH) was used to detect infection of HPV in 33 cases of OSCC and 76 cases of OLK, including 30 cases of hyperplasia, 15 cases of mild OED, 15 cases of moderate OED and 16 cases of severe OED.Results: The prevalence of HPV in OLP samples was higher (12.12%, 8/66) than that of OLK (2.59%, 3/116) (χ2=4.666, P=0.031) and OSCC(7.14%, 2/28, χ2=0.513, P=0.474). The prevalence of HPV in OSCC (7.14%, 2/28) was higher than that of OLK (2.59%, 3/116), and no significant difference was found. There was only one case of smoke spot and statistical analysis was not carried out. ISH was used to detect type 16/18 and type 31/33 HPV DNA in 109 cases of oral mucosal lesions in paraffin sections and only one case of OSCC was HPV positive. Thirty-seven cases were detected by HC-Ⅱ and ISH methods at the same time. The same negative results by the two methods were found in 94.6% samples (35/37). In the other two samples, one was OSCC with early infiltration and the other was OLK with hyperplasia, The HC-Ⅱ results were positive while the ISH results were negative. The patients with OLP and HPV testing results were followed up and the average follow-up period was (36.2±10.5) months. It was found that three of them had a malignant transformation, and the malignant transformation rate of HPV positive patients was 12.50% (1/8), which was higher than that of HPV negative patients (3.45%, 2/58), and the difference was not statistically significant, P= 0.249.Conclusion: HC-Ⅱ assay was more sensitive in detecting HPV infection of oral mucosal lesions than ISH. The results of this study showed that there was insufficient evidence for taking HPV infection as a predictor of OLK carcinogenesis. Patients suffering from OLP were in a precancerous condition. The prevalence of HPV in OLP patients of this study was higher than that in OLK and OSCC patients, suggesting that for some reason, OLP patients were susceptible to HPV. HPV testing can be considered as routine in patients with OLP, and HC-Ⅱ assay was recommended. And patients with OLP and HPV positive should be followed up regularly.

Key words: Papillomaviridae, DNA, viral, Leukoplakia, oral, Lichen planus, oral, Mouth neoplasms

中图分类号: 

  • R739.85
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