Esophageal squamous cell carcinoma metachronous to head and neck cancers

Gianluca Businello, Matteo Fassan, Silvia Degasperi, Giulia Traverso, Melania Scarpa, Imerio Angriman, Andromachi Kotsafti, Ignazio Castagliuolo, Marta Sbaraglia, Romeo Bardini, Marco Scarpa

Research output: Contribution to journalArticlepeer-review


BACKGROUND: In some HNSCC patients, a metachronous ESCC may develop. No information is available on the HNSCC-associated ESCCs microenvironment and etiology.

METHODS: Among 134 ESCCs surgically treated between 2009 and 2015, a series of 6 HNSCC-associated ESCCs was collected. A series of 12 sex-, age- and stage-matched ESCCs with no previous oncological medical history was selected for comparison. Histologic assessment of intratumoral inflammatory infiltration and immunohistochemistry for CD4, CD8, CD80, PD1, PD-L1 and p53 were performed. HPV detection/genotyping was assessed by PCR single step and reverse line blot.

RESULTS: HPV DNA was negative in all the HNSCC-associated ESCCs. In comparison to non-HNSCC-associated carcinomas, the 6 cases presented a lower lymphomonocytic infiltration, which also corresponded to a lower prevalence of CD4 + T cell infiltration and, 5/6 cases presented a PD-L1 CPS ≥ 1. All the HNSCC-associated ESCCs resulted positive for p53 immunostaining in ≥50 % of cancer cells.

CONCLUSION: Our study suggests that HPV infection is not an etiological factor associated to ESCC after HNSCC. On the other hand, p53 overexpression is a common finding. Moreover, our data suggest that an altered immune microenvironment, conditioned by a dysregulation in lymphomonocytic infiltration, may be a crucial factor allowing the occurrence of a metachronous ESCC.

Original languageEnglish
Article number153346
Pages (from-to)1-5
Number of pages5
JournalPathol. Res. Pract.
Publication statusPublished - Mar 2021


  • Aged
  • Carcinoma, Squamous Cell/pathology
  • Esophageal Neoplasms/etiology
  • Esophageal Squamous Cell Carcinoma/metabolism
  • Female
  • Head and Neck Neoplasms/etiology
  • Humans
  • Male
  • Middle Aged
  • Squamous Cell Carcinoma of Head and Neck/etiology
  • T-Lymphocytes/pathology
  • Tumor Microenvironment/immunology


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