Tong Charles C L, Lin Xiang, Seckar Tyler, Koptyra Mateusz, Kohanski Michael A, Cohen Noam A, Kennedy David W, Adappa Nithin D, Papagiannopoulos Peter, Kuan Edward C, Baranov Esther, Jalaly Jalal B, Feldman Michael D, Storm Phillip B, Resnick Adam C, Palmer James N, Wei Zhi, Robertson Erle S
Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, USA.
Int Forum Allergy Rhinol. 2023 Nov;13(11):2055-2062. doi: 10.1002/alr.23182. Epub 2023 May 28.
Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The role of human papillomavirus (HPV) in its pathogenesis has been controversial. The purpose of this study was to determine the virome associated with IP, with progression to carcinoma in situ (CIS), and invasive carcinoma.
To determine the HPV-specific types, a metagenomics assay that contains 62,886 probes targeting viral genomes in a microarray format was used. The platform screens DNA and RNA from fixed tissues from eight controls, 16 IP without dysplasia, five IP with CIS, and 13 IP-associated squamous cell carcinoma (IPSCC). Paired with next-generation sequencing, 48 types of HPV with 857 region-specific probes were interrogated against the tumors.
The prevalence of HPV-16 was 14%, 42%, 70%, and 73% in control tissue, IP without dysplasia, IP with CIS, and IPSCC, respectively. The prevalence of HPV-18 had a similar progressive increase in prevalence, with 14%, 27%, 67%, and 74%, respectively. The assay allowed region-specific analysis, which identified the only oncogenic HPV-18 E6 to be statistically significant when compared with control tissue. The prevalence of HPV-18 E6 was 0% in control tissue, 25% in IP without dysplasia, 60% in IP with CIS, and 77% in IPSCC.
There are over 200 HPV types that infect human epithelial cells, of which only a few are known to be high-risk. Our study demonstrated a trend of increasing prevalence of HPV-18 E6 that correlated with histologic severity, which is novel and supports a potential role for HPV in the pathogenesis of IP.
内翻性乳头状瘤（IP）是一种鼻窦肿瘤，具有众所周知的恶变潜能。人乳头瘤病毒（HPV）在其发病机制中的作用一直存在争议。本研究的目的是确定与IP、原位癌（CIS）进展及浸润癌相关的病毒组。
为确定HPV的特定类型，使用了一种宏基因组学检测方法，该方法以微阵列形式包含62,886个靶向病毒基因组的探针。该平台筛选来自8名对照、16例无发育异常的IP、5例伴有CIS的IP以及13例IP相关鳞状细胞癌（IPSCC）的固定组织中的DNA和RNA。结合下一代测序，针对肿瘤检测了48种HPV及857个区域特异性探针。
HPV-16在对照组织、无发育异常的IP、伴有CIS的IP以及IPSCC中的患病率分别为14%、42%、70%和73%。HPV-18的患病率也有类似的逐渐上升趋势，分别为14%、27%、67%和74%。该检测允许进行区域特异性分析，与对照组织相比，仅鉴定出致癌性HPV-18 E6具有统计学意义。HPV-18 E6在对照组织中的患病率为0%，在无发育异常的IP中为25%，在伴有CIS的IP中为60%，在IPSCC中为77%。
有超过200种HPV类型可感染人类上皮细胞，其中只有少数被认为是高危型。我们的研究显示HPV-18 E6患病率有随组织学严重程度增加的趋势，这是新颖的，支持了HPV在IP发病机制中的潜在作用。
