Abstract：
The sinonasal tract is considered a second hotspot for human papillomavirus (HPV)-related tumors in the head and neck, with HPV being identified in up to 62% of squamous cell carcinomas (SCCs) and 38% of papillomas. There is limited data from geographical regions with low prevalence of high-risk (HR)-HPV on the association of HR-HPV in sinonasal neoplasms and on utility of p16 as a surrogate marker. p16 immunohistochemistry, HR-HPV mRNA ISH and quantitative real-time PCR (qPCR) were performed on a retrospective cohort of sinonasal papillomas and SCCs. KRAS mutation analysis was done in oncocytic papillomas. p16 positivity was present in 22/142 cases (15.5%) including eight inverted papillomas, one oncocytic papilloma (OP), and 13 SCC. Among these, mRNA ISH showed HR-HPV in the OP and two SCC, while another SCC was found to harbour HPV18 by qPCR. Two HPV-associated SCCs had foci of OP. mRNA ISH was negative in all p16 negative cases. p16 immunohistochemistry showed 68% concordance with mRNA ISH, and had sensitivity and negative predictive value of 100%; specificity was 67%, and positive predictive value was 14.3%. Association with HR-HPV in sinonasal papillomas and SCC is rare, and may be seen in cases demonstrating oncocytic morphology. p16 immunohistochemistry has low specificity and positive predictive value in low-prevalence populations; thus, reflex direct HR-HPV testing should be performed in p16 immunopositive cases. This two-step approach is viable in resource-limited settings, as the proportion of p16 positive cases is small.
摘要：
鼻腔鼻窦被认为是头颈部人类乳头状瘤病毒（HPV）相关肿瘤的第二热点，在高达62%的鳞状细胞癌（SCC）和38%的乳头状瘤中发现了HPV。来自高风险（HR）-HPV患病率低的地理区域的数据有限，关于HR-HPV在鼻窦肿瘤中的关联以及p16作为替代标记的实用性。p16免疫组织化学，对鼻腔鼻窦乳头状瘤和SCC的回顾性队列进行了HR-HPVmRNAISH和定量实时PCR（qPCR）。在嗜酸细胞乳头状瘤中进行KRAS突变分析。p16阳性22/142例(15.5%)，包括8例内翻性乳头状瘤，一例嗜酸细胞乳头状瘤（OP），13SCC其中,ISHmRNA在OP和两个SCC中显示HR-HPV，而通过qPCR发现另一个SCC携带HPV18。两个HPV相关的SCC有OP灶。所有p16阴性病例ISHmRNA均为阴性。p16免疫组织化学显示与ISHmRNA的一致性为68%，敏感性和阴性预测值为100%；特异性为67%，阳性预测值为14.3%。与HR-HPV的关系在鼻窦乳头状瘤和SCC是罕见的，并且可以在表现出嗜酸细胞形态的病例中看到。p16免疫组织化学在低患病率人群中具有低特异性和阳性预测价值；因此，在p16免疫阳性病例中,应进行反射性直接HR-HPV检测.这种两步方法在资源有限的环境中是可行的，p16阳性病例比例较小。
