Hooper Jody E, Hebert Jessica F, Schilling Amy, Gross Neil D, Schindler Joshua S, Lagowski James P, Kulesz-Martin Molly, Corless Christopher L, Morgan Terry K
Departments of *Pathology ‡Otolaryngology §Dermatology Research Division †Knight Diagnostic Laboratory, Oregon Health and Science University, Portland, OR.
Appl Immunohistochem Mol Morphol. 2015 Apr;23(4):266-72. doi: 10.1097/PDM.0000000000000036.
High-risk human papillomavirus (HPV) infection is a common cause of oropharyngeal squamous cell carcinoma, especially in young male nonsmokers. Accurately diagnosing HPV-associated oral cancers is important, because they have a better prognosis and may be treated differently than smoking-related oral carcinomas. Various methods have been validated to test for high-risk HPV in cervical tissue samples, and they are in routine clinical use to detect dysplasia before it progresses to invasive disease. Similarly, future screening for HPV-mediated oropharyngeal dysplasia may identify patients before it progresses. Our objective was to compare 4 of these methods in a retrospective series of 87 oral and oropharyngeal squamous cell carcinomas that had archived fresh-frozen and paraffin-embedded tissue for evaluation. Patient age, sex, smoking history, and tumor location were also recorded. DNA prepared from fresh-frozen tissue was tested for HPV genotypes by multiplex polymerase chain reaction analysis, and high-risk HPV screening was carried out using Hybrid Capture 2 and Cervista. Histologic sections were immunostained for p16. HPV-positive outcome was defined as agreement between at least 2 of the 3 genetic tests and used for χ analysis and calculations of diagnostic predictive value. As expected, high-risk HPV-positive oral cancers were most common in the tonsil and base of the tongue (oropharynx) of younger male (55 vs. 65 y) (P=0.0002) nonsmokers (P=0.01). Most positive cases were HPV16 (33/36, 92%). Hybrid Capture 2 and Cervista were as sensitive as polymerase chain reaction and had fewer false positives than p16 immunohistochemical staining.
高危型人乳头瘤病毒（HPV）感染是口咽鳞状细胞癌的常见病因，在年轻男性非吸烟者中尤为常见。准确诊断HPV相关的口腔癌很重要，因为其预后较好，治疗方式可能与吸烟相关的口腔癌不同。多种方法已被验证可用于检测宫颈组织样本中的高危型HPV，并且在常规临床中用于在发育异常进展为浸润性疾病之前进行检测。同样，未来对HPV介导的口咽发育异常的筛查可能在其进展之前识别出患者。我们的目的是在一项回顾性研究中比较这4种方法，该研究纳入了87例口腔和口咽鳞状细胞癌，这些病例均存档有新鲜冷冻和石蜡包埋组织用于评估。还记录了患者的年龄、性别、吸烟史和肿瘤位置。通过多重聚合酶链反应分析检测新鲜冷冻组织中提取的DNA的HPV基因型，并使用杂交捕获2法和Cervista法进行高危型HPV筛查。对组织学切片进行p16免疫染色。HPV阳性结果定义为3种基因检测中至少2种检测结果一致，并用于χ分析和诊断预测值的计算。正如预期的那样，高危型HPV阳性的口腔癌在年轻男性（55岁对65岁）（P = 0.0002）非吸烟者（P = 0.01）的扁桃体和舌根（口咽）中最为常见。大多数阳性病例为HPV16（33/36，92%）。杂交捕获2法和Cervista法与聚合酶链反应一样敏感，且假阳性比p16免疫组化染色少。
