The potential role of immunity in the development of early distant metastases in locoregionally treated oral squamous cell carcinoma

Abstract

Head and neck malignancies usually lead to locoregional recurrence most often than distant recurrence; however distant metastasis is still challenging. The identification of the risk factors responsible for the incidence of early distant metastasis is crucial and plays an important role in foreseeing the probability of incidence of early distant metastasis. Therefore, we hypothesize that, in advanced oral cavity squamous cell carcinomas (OCSCC), the tumors generate a strong immunogenic response and once the tumor is surgically removed, there exists a withdrawal of this immunogenic response and this could be the genesis for the occurrence of early distant metastasis in these patients. To evaluate the role of immunity, we conducted a retrospective review of 10 patients of OCSCC who achieved local control following definitive therapy and later developed distant metastases within six months after treatment. Out of 10 patients, 60% of the patient’s primary tumor histology is poorly differentiated squamous cell carcinoma, 50% of patients had a pathological N3b disease, and bone invasion is reported in 40% of patients. Lymphovascular invasion was found in 90% of the patients, while the extranodal extension was found in 60% of the patients. Out of 10 patients, 5 patients underwent tumor microenvironment panel and immunohistochemistry study. All five patients exhibited immunogenic “hot” tumors with more than 50% CD3 count expression suggesting that the immunogenic “hot” tumors are a significant risk factor for early distant metastasis. Results provide evidence that early distant metastasis in advanced OCSCC is probably a consequence of loss of immunogenic response after removal of a large tumor. Further systemic studies are recommended to validate this hypothesis.