Esophageal squamous cell carcinoma metachronous to head and neck cancers.

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.