Abstract
BackgroundWe aimed to clarify the possible role of human papillomavirus (HPV) infection in the malignant transformation of sinonasal inverted papilloma (IP).MethodsSubjects comprised 32 patients with chronic rhinosinusitis (CRS), 17 with IP, 5 with IP and squamous cell carcinoma (IP + SCC), and 16 with primary sinonasal SCC. HPV presence, viral loads, and physical status were investigated using polymerase chain reaction. Retinoblastoma (pRb), p53, and p16INK4a gene products were investigated by immunohistochemistry.ResultsHPV DNA was detected in 6.3 % of cases with CRS, 29.4 % with IP, 40 % with IP + SCC, and 25 % with SCC. IP cases had significantly higher HPV presence than CRS cases (p = 0.04). High-risk HPV-16 was the most frequently encountered subtype (10/13, 76.9 %). HPV-16 viral loads varied from 2.5 to 7953 E6 copies/50 ng genomic DNA. Patients in the SCC and IP + SCC groups had significantly higher viral loads than those in the IP and CRS groups (p < 0.01). All SCC and IP + SCC patients with HPV-16 demonstrated mixed-type integration, whereas 4 of 5 HPV-16 patients in the IP and CRS groups showed episomal type infection (p = 0.04). Positivity to pRb was found in 78.1 % of CRS, 35.3 % of IP, and 68.8 % of SCC cases. The presence of HPV DNA negatively correlated with pRb expression in SCC (p = 0.029) and IP (P = 0.049) groups. Although 62.5 % of SCC cases exhibited p53 positivity, only 5.9 % of IP, and no CRS cases were positive. Regardless of HPV status, p16INK4a positivity was frequently detected in IP cases (82.4 %), less in SCC (12.5 %) cases, and was not detected in the CRS group. Neither the IP nor SCC cohorts showed any correlation between HPV presence and the expression of either p53 or p16INK4a.ConclusionsHPV infection was more frequent in the IP, IP + SCC, and SCC groups than the CRS group. Higher viral loads and integration observed in the IP + SCC and SCC groups, and an inverse correlation between HPV presence and positive pRb indicated that persistent infection and integration play a part in tumorigenesis and malignant transformation in certain IP cases. However, p16INK4a is not a reliable surrogate marker for HPV infection in IP.
Highlights
We aimed to clarify the possible role of human papillomavirus (HPV) infection in the malignant transformation of sinonasal inverted papilloma (IP)
We previously reported that HPV infection is involved in the pathogenesis of IP and that high viral loads and integration of HPV may play important roles in malignant transformation [10]
Higher HPV-16 viral loads were detected in the Squamous cell carcinoma (SCC) and IP + SCC groups, compared with the IP and chronic rhinosinusitis (CRS) groups. These findings suggest that persistent infection and the integration of high-risk HPV types play important roles in the malignant transformation of IP
Summary
We aimed to clarify the possible role of human papillomavirus (HPV) infection in the malignant transformation of sinonasal inverted papilloma (IP). Of these, inverted papilloma (IP), a benign neoplasm, has unique clinical characteristics; of note are its high rates of recurrence and malignant transformation. Two studies by Beck et al found that 63 % of IP cases were positive for HPV DNA, and the presence of HPV sequences predicted the recurrence of inverted papilloma [4, 5]. These studies found that patients with HPV types 16 or 18 have a higher rate of associated malignancy than patients with HPV 6 or 11 [5]. There continues to be discussion over whether there is a significant correlation between the development of malignant transformation in IP and HPV types [11, 16, 20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
