title: Epithelial-mesenchymal transition in human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma.
abstract: High-risk human papillomavirus (HPV) infection is associated with carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC) and patients with HPV-positive tumors have a significantly favorable prognosis. However, the underlying mechanism of this favorable clinical outcome remains unclear. Epithelial-mesenchymal transition (EMT) causes aggressiveness of cancer cells and we investigated the expression of the EMT markers and analyzed their correlation with HPV status and prognosis in order to examine the treatment response of HPV-positive OPSCCs. A total of 79 patients with OPSCC were examined in the present study. All high-risk HPV infections were determined with the multiplex PCR kit from each formalin-fixed paraffin-embedded (FFPE) sample. We performed immunohistochemical staining for E-cadherin and vimentin. Expression of the markers was graded and we statistically analyzed the correlation between tumor, node, metastasis (TNM) stages and prognosis. High-risk HPV-positive tumors were detected in 23 cases. The five‑year survival rate in HPV-positive and -negative tumors was 82.7 and 48.3%, respectively. High E-cadherin expression rate in HPV-negative samples was 76.7% and 43.4% in HPV-positive samples (p=0.007). Vimentin expression did not show a difference between HPV-positive and -negative tumors. HPV-negative patients presented significantly greater heterogeneity of E-cadherin expression compared to HPV-positive patients (p=0.0349). HPV-positive OPSCCs originally lost their epithelial cell phenotype compared with HPV-negative tumors. Therefore, the paradoxical favorable prognosis of HPV-positive OPSCC may be due to the intratumor homogeneity in EMT.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Hatakeyama
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Mizumachi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sakashita
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kano
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Homma
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052162:Human papillomavirus 16 / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology / Q000821:virology; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D011379:Prognosis; D014746:Vimentin / Q000096:biosynthesis
chemical_list: D015820:Cadherins; D014746:Vimentin