Human papillomavirus infection and immunohistochemical expression of cell cycle proteins pRb, p53, and p16 INK4a in sinonasal diseases

Infectious Agents and Cancer

Mikio Suzuki¹  Akira Ganaha¹  Taro Ikegami¹  Takeshi Shimizu³  Hideaki Kouzaki³  Takayuki Uehara¹  Shinya Agena¹  Sen Matayoshi¹  Asanori Kyuna¹  Shunsuke Kondo¹  Hiroyuki Maeda¹  Zeyi Deng²  Masahiro Hasegawa¹  Yukashi Yamashita¹ 

[1] Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan;Department of Otorhinolaryngology, Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China;Department of Otolaryngology, Head and Neck Surgery, Shiga University of Medical Science, Otsu 520-2192, Japan

关键词: Sinonasal disease;    Viral load;    Integration;    Malignant transformation;    Inverted papilloma;    Cell cycle protein;    Human papillomavirus;   

Others  :  1223386
DOI  :  10.1186/s13027-015-0019-8

 received in 2015-05-07, accepted in 2015-07-08,  发布年份 2015

【 摘 要 】

Background

We aimed to clarify the possible role of human papillomavirus (HPV) infection in the malignant transformation of sinonasal inverted papilloma (IP).

Methods

Subjects 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 p16 ^INK4agene products were investigated by immunohistochemistry.

Results

HPV 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, p16 ^INK4apositivity 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 p16 ^INK4a .

Conclusions

HPV 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, p16 ^INK4ais not a reliable surrogate marker for HPV infection in IP.

【 授权许可】

   
2015 Yamashita et al.

【 图 表 】

Fig. 1.

Fig. 2.

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