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Yamashita Y, Hasegawa M, Deng Z, et al. Human papillomavirus infection and immunohistochemical expression of cell cycle proteins pRb, p53, and p16(INK4a) in sinonasal diseases. Infect Agent Cancer. 2015;10:23doi: 10.1186/s13027-015-0019-8.
Yamashita, Y., Hasegawa, M., Deng, Z., Maeda, H., Kondo, S., Kyuna, A., Matayoshi, S., Agena, S., Uehara, T., Kouzaki, H., Shimizu, T., Ikegami, T., Ganaha, A., & Suzuki, M. (2015). Human papillomavirus infection and immunohistochemical expression of cell cycle proteins pRb, p53, and p16(INK4a) in sinonasal diseases. Infectious agents and cancer, 1023. https://doi.org/10.1186/s13027-015-0019-8
Yamashita, Yukashi, et al. "Human papillomavirus infection and immunohistochemical expression of cell cycle proteins pRb, p53, and p16(INK4a) in sinonasal diseases." Infectious agents and cancer vol. 10 (2015): 23. doi: https://doi.org/10.1186/s13027-015-0019-8
Yamashita Y, Hasegawa M, Deng Z, Maeda H, Kondo S, Kyuna A, Matayoshi S, Agena S, Uehara T, Kouzaki H, Shimizu T, Ikegami T, Ganaha A, Suzuki M. Human papillomavirus infection and immunohistochemical expression of cell cycle proteins pRb, p53, and p16(INK4a) in sinonasal diseases. Infect Agent Cancer. 2015 Aug 04;10:23. doi: 10.1186/s13027-015-0019-8. eCollection 2015. PMID: 26244053; PMCID: PMC4524447.
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Infect Agent Cancer. 2015 Aug 04;10:23. doi: 10.1186/s13027-015-0019-8. eCollection 2015.

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

Infectious agents and cancer

Yukashi Yamashita, Masahiro Hasegawa, Zeyi Deng, Hiroyuki Maeda, Shunsuke Kondo, Asanori Kyuna, Sen Matayoshi, Shinya Agena, Takayuki Uehara, Hideaki Kouzaki, Takeshi Shimizu, Taro Ikegami, Akira Ganaha, Mikio Suzuki

Affiliations

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

PMID: 26244053 PMCID: PMC4524447 DOI: 10.1186/s13027-015-0019-8

Abstract

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(INK4a) gene 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(INK4a) 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 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(INK4a) is not a reliable surrogate marker for HPV infection in IP.

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

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