HPV-Associated Tonsillar Intraepithelial Neoplasia and Oral High-Risk HPV mRNA as a Candidate Biomarker
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: ABSTRACT Early detection of human papillomavirus (HPV)-associated oropharyngeal cancer is an unmet need, as its premalignant lesions remain unestablished. We hypothesized that such lesions exist in individuals with oral high-risk HPV (HR-HPV) mRNA. We preoperatively screened 1,180 individuals undergoing tonsillectomy due to benign conditions and detected five with oral HR-HPV mRNA. Serial sectioning of the entire excised tonsils identified HPV-associated intraepithelial lesions in three of these five individuals. A similar lesion was identified in an additional individual with oral HPV16 infection with unknown oral HR-HPV mRNA status. Intraepithelial lesions in two individuals were HPV16-associated and showed moderate-to-severe atypia, whereas those in the other two individuals were associated with other HR-HPV and showed minimal-to-mild atypia. Based on HPV life cycle, the former were classified as transforming lesions and the latter as productive-to-intermediate lesions. Spatial transcriptomic analysis revealed molecular profiles intermediate between those of normal epithelium and HPV-associated oropharyngeal cancer. These findings establish the first evidence for HPV-associated tonsillar premalignant lesions and suggest oral HR-HPV mRNA as a candidate biomarker.
Authors: Masashi Mori, Hidenori Tanaka, Masami Suzuki, Kansuke Kido, Kazuya Ogawa, Noah Sasa, Toshihiro Kishikawa, Nagayasu Egawa, Daichi Maeda, Masafumi Horie, Kiyohito Hosokawa, Motoyuki Suzuki, Hiroshi Kato, Kazuki Hayashi, Syusuke Okamoto, Tadashi Yoshii, Shotaro Harada, Tetsuo Morihana, Sho Obata, Satoru Uetsuka, Suetaka Nishiike, Naoki Ashida, Rumi Kambara, Tsutomu Sano, Kayoko Higashi-Shingai, Takayuki Kawashima, Aya Kamakura, Kenji Mitani, Hayato Mori, Rentaro Watanabe, Tomoki Yasuoka, Eiichi Morii, Hidenori Inohara
Language: English
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7222914659