Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma

Takafumi Nakano, Hidetaka Yamamoto, Torahiko Nakashima, Toshimitsu Nishijima, Masanobu Satoh, Yui Hatanaka, Hideki Shiratsuchi, Ryuji Yasumatsu, Satoshi Toh, Shizuo Komune, Yoshinao Oda

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Abstract

Summary Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P =.0026 and P =.0026) and nonkeratinizing histology (P =.0002 and P =.0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P =.0667) and worse overall survival (P <.0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P <.0001 and P <.0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy.

Original languageEnglish
Pages (from-to)51-61
Number of pages11
JournalHuman Pathology
Volume50
DOIs
Publication statusPublished - Apr 1 2016

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Epidermal Growth Factor Receptor
Squamous Cell Carcinoma
Papillomavirus Infections
In Situ Hybridization
erbB-1 Genes
Gene Dosage
Chemoradiotherapy
Survival
Proteins
Histology
Immunohistochemistry
Biopsy

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma. / Nakano, Takafumi; Yamamoto, Hidetaka; Nakashima, Torahiko; Nishijima, Toshimitsu; Satoh, Masanobu; Hatanaka, Yui; Shiratsuchi, Hideki; Yasumatsu, Ryuji; Toh, Satoshi; Komune, Shizuo; Oda, Yoshinao.

In: Human Pathology, Vol. 50, 01.04.2016, p. 51-61.

Research output: Contribution to journalArticle

Nakano, Takafumi ; Yamamoto, Hidetaka ; Nakashima, Torahiko ; Nishijima, Toshimitsu ; Satoh, Masanobu ; Hatanaka, Yui ; Shiratsuchi, Hideki ; Yasumatsu, Ryuji ; Toh, Satoshi ; Komune, Shizuo ; Oda, Yoshinao. / Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma. In: Human Pathology. 2016 ; Vol. 50. pp. 51-61.
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AU - Nishijima, Toshimitsu

AU - Satoh, Masanobu

AU - Hatanaka, Yui

AU - Shiratsuchi, Hideki

AU - Yasumatsu, Ryuji

AU - Toh, Satoshi

AU - Komune, Shizuo

AU - Oda, Yoshinao

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AB - Summary Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P =.0026 and P =.0026) and nonkeratinizing histology (P =.0002 and P =.0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P =.0667) and worse overall survival (P <.0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P <.0001 and P <.0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy.

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