Human papillomavirus and infiltration of CD8- and Foxp3-positive immune cells in sinonasal inverted papillomas

Abstract

Background: Sinonasal inverted papilloma (IP) is a benign tumor with a high risk of local recurrence and a potential to malignify and Human papillomavirus (HPV) has been suggested an etiological factor. p16INK4a (p16) overexpression is considered a surrogate marker for HPV, but whether p16 and HPV correlate to IP is uncertain. Besides, a prognostic role of tumor infiltrating lymphocytes (TILs) are observed in many tumors, however their role in IP is sparsely studied.

Aims/objectives: We hence analyzed IPs for the presence and the prognostic role of HPV and p16 overexpression together with CD8+ and FoxP3+ TILs in a population-based study.

Material and methods: 98 IP patients diagnosed 2001–2010 were identified from the Swedish Cancer Registry and analyzed for HPV by PCR and p16, CD8 and FoxP3 was by immunohistochemistry.

Results: In total, 12.2% of the IPs were HPV-positive (nine HPV-11, two HPV-6 and one HPV-45). Patients with HPV-positive lesions were younger (p = .003) and tended to present with more dysplasia. No correlation was observed between TILs and prognosis.

Conclusions and significance: Our data suggests that patients with HPV-positive IPs present with different clinical characteristics, suggesting possibly different disease entities. Moreover, recurrences may occur >5 years, which should be considered in the follow-up.

Chinese abstract

背景：鼻腔内翻乳头状瘤（IP）是一种良性肿瘤, 局部复发风险高, 有潜在的恶性化。人乳头状瘤病毒（HPV）被认为是其病因。p16INK4a（p16）过表达被认为是HPV的替代标记, 但p16和HPV是否与IP相关尚不确定。此外, 观察到肿瘤浸润淋巴细胞（TIL）在许多肿瘤中的预后作用, 但其对IP的作用却很少被研究。

目的：在一项基于人群的研究中, 我们分析了人乳头状瘤病毒以确定HPV和p16过表达以及CD8+和FoxP3+TIL的存在和预后作用。

材料和方法：从瑞典癌症登记处对2001-2010年确诊的98例IP患者进行了鉴定, 并通过聚合酶链反应（PCR）对其进行了HPV分析, 通过免疫组织化学对p16、CD8和FoxP3进行了分析。

结果：12.2%的IP为HPV阳性（9例HPV-11, 2例HPV-6, 1例HPV-45）。HPV阳性病变患者年龄较轻（p =.003）, 并倾向于出现更多的发育不良。TIL与预后无相关性。

结论和意义：我们的数据表明, HPV阳性IP患者具有不同的临床特征, 提示可能存在不同的疾病实体。此外, 复发时间可能超过5年, 应在随访中予以考虑。

Keywords:

• Dysplasia
• human papillomavirus
• inverted papilloma
• lymphocytes and recurrence

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Financial support provided by The ACTA Otolaryngologica Foundation, The Swedish Society of Medicine, the Nachmanson Foundation through The Swedish ENT Association for Otorhinolaryngology, Head and Neck surgery (SFOHH) and the Swedish Society for Medical Research (SSMF).