Purpose and methods
A retrospective study was conducted to identify and assess potential clinical and molecularbiological risk factors for development and recurrence of sinonasal papillomas (i.e. ...inverted (IP), fungiform (FP), and oncocytic papillomas (OCP)). Investigated risk factors included age, gender, tumor size and localization, tobacco smoking, regular alcohol consumption, essential hypertension, anticoagulant medication, allergies, surgical approach, and HPV infection. Risk factors were evaluated by regression analysis.
Results
Apart from age and incomplete tumor resection, the recurrence of Schneiderian papillomas is independent of conventional risk factors. Patients in this study displayed higher HPV infections rates in IP (38.8%) and in FP (100%) than in healthy mucosa, which is reported 0–5.8% in Germany and central Europe. The proportion of HPV-positive IP decreased with advanced tumor stages: 100% HPV positivity of T1 IP (2/2), 40.9% of T2 IP (9/22), and 35.7% of T3 IP (20/56). Most commonly detected HPV types were HPV 6, 11, and 16; however, patients in this study also displayed HPV types that have rarely or not at all been described in sinonasal papillomas before, such as HPV 58, 42, 83, and 91. Recurrent sinonasal papillomas displayed higher rates of HPV infections than non-recurrent tumors.
Conclusions
Young age at initial diagnosis and incomplete tumor resection are risk factors for recurrence of sinonasal papillomas. Our data suggest that HPV infection supports development and/or perpetuation of sinonasal papillomas. Additionally, sinonasal papillomas seem to display a unique subset of HPV genotypes, including genotypes that have not often been described before.
Sinonasal papillomas are rare, usually benign tumors arising from the Schneiderian membrane. Human papillomaviruses (HPV) can infect differentiating skin and mucosal cells and can induce uncontrolled ...growth patterns. Their effect on development of sinonasal papillomas has been discussed controversially in recent years. A monocentric, retrospective study was conducted to investigate histopathologic features of sinonasal papillomas and to establish an assay for HPV detection and genotyping in papillomas. Schneiderian papillomas are divided into three groups according to histopathologic features: the largest group are inverted papillomas, followed by fungiform (exophytic) and oncocytic papillomas. HPV screening was performed with high sensitivity by PCR employing My09/11 and 125 consensus primers. Adding a third primer pair (GP5+/GP6+) d increase sensitivity. Reverse hybridization microarrays achieved HPV genotyping better than pyrosequencing in our setting. HPV infection rates were higher in papillomas (46.7%) than infection rates reported for healthy mucosa (up to 13%). P16(INK4a) was not a reliable surrogate marker for HPV infection in sinonasal papillomas. Data from our study endorses the hypothesis that HPV infection promotes formation of sinonasal papillomas. However, apart from HPV genotypes that are frequently found in e.g. anogenital lesions (such as 6, 11, or 16), tissue samples of sinonasal papillomas also displayed infection with “rare” HPV types (such as 58, 42, 83, or 91).
Sinonasal papillomas are characterized by their potential for frequent recurrences and malignant progression. Currently, the role of human papillomavirus (HPV) infection in sinonasal papillomas is ...unclear. A study was conducted to elucidate the impact of HPV infection on recurrence and malignant progression of sinonasal papillomas. One hundred and seven patients with 151 tumors could be examined. One hundred and one patients suffered from benign papilloma, mostly inverted papillomas (IP); six patients suffered from carcinomas in situ and squamous cell carcinomas (SCC) ex‐IP. Recurrent IP were more often HPV‐positive than non‐recurrent tumors (38.8% vs. 60%–65%). Low‐risk (LR) HPV infection (especially HPV 6) increased the risk of tumor recurrences (p = 0.0385 and p = 0.0556, respectively). IP and oncocytic papillomas (both lesions are known for their malignant potential) were more often high‐risk (HR) HPV‐positive (15.5% and 16.7%) than fungiform papilloma (which usually does not progress to carcinoma). CIS and SCC ex‐IP displayed higher HPV rates than benign IP (83.3% vs. 38.8%), especially higher rates of HR‐HPV (66.7% vs. 23.8%, p = 0.0415). Data from this study endorse the hypothesis that recurrence of sinonasal papillomas is promoted by LR‐HPV infection and that malignant progression of IP is promoted by HR‐HPV infection.
The impact of HPV infection on recurrences and malignant transformation of sinonasal papillomas is elucidated. HPV infection rate is significantly higher in recurrent papillomas than in non‐recurrent and the highest in papillomas with malignant progression. Most frequent HPV subtypes are HPV 6 in benign recurrent tumors, and HPV 16, 45, and 66 in malignant tumors, along with HPV 90 which is currently described for the first time in sinonasal papillomas. The data suggest that HPV infection is a risk factor for tumor recurrences. Malignant progression seems to be supported by high‐risk HPV genotypes (i.e., 16, 45, 66, and probably 90).
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