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Updated: Nov 18, 2025

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Esophageal squamous cell carcinoma metachronous to head and neck cancers
Gianluca Businello1, Matteo Fassan1, Silvia Degasperi2
1Dept. of Medicine, Pathology Unit, University of Padua, Padua, Italy.
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.
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