Human Papillomavirus Infection and <i>EGFR</i> Exon 20 Insertions in Sinonasal Inverted Papilloma and Squamous Cell Carcinoma

This study aimed to clarify the roles of high-risk human papillomavirus (HR-HPV) infection and epidermal growth factor receptor (EGFR) exon 20 mutations in sinonasal inverted papilloma (IP) and sinonasal squamous cell carcinoma (SNSCC). Samples were collected from 20 cases with IP, 7 with IP and squ...

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Main Authors: Hitoshi Hirakawa, Taro Ikegami, Norimoto Kise, Hidetoshi Kinjyo, Shunsuke Kondo, Shinya Agena, Narumi Hasegawa, Junko Kawakami, Hiroyuki Maeda, Mikio Suzuki
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Journal of Personalized Medicine
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Online Access:https://www.mdpi.com/2075-4426/13/4/657
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Summary:This study aimed to clarify the roles of high-risk human papillomavirus (HR-HPV) infection and epidermal growth factor receptor (EGFR) exon 20 mutations in sinonasal inverted papilloma (IP) and sinonasal squamous cell carcinoma (SNSCC). Samples were collected from 20 cases with IP, 7 with IP and squamous cell carcinoma (IP-SCC)<i>,</i> and 20 with SNSCC and examined for HPV infection and EGFR exon 20 mutations. Low- or high-risk HPV DNA was observed in 25% of IP, 57.1% of IP-SCC, and 35% of SNSCC cases. Transcriptionally active HR-HPV infections in IP-SCC and SNSCC, accompanied by p16 overexpression, were observed in 28.5% and 25% of cases, respectively. Heterozygous <i>EGFR</i> exon 20 amino acid insertions (ex20ins), located between amino acids 768–774, were observed in 45% of IP, 28.5% of IP-SCC, and 0% of SNSCC and chronic sinusitis cases. EGFR phosphorylation sites were located at tyrosine (Y) 845, Y1068, Y1086, and Y1197 and induced PI3K/AKT/mTOR activation. The phosphorylation pattern of EGFR with ex20ins resembled that of HPV-related SNSCC and oropharyngeal cancer. The transcriptionally active HR-HPV infection and ex20ins might be responsible for the pathogenesis of IP-SCC cases with different fashions. Since IP-SCC might be a multifactorial disease, further investigation is needed to understand IP-SCC etiology.
ISSN:2075-4426