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X chromosome inactivation is the epitome of epigenetic regulation and long non-coding ribonucleic acid function. The differentiation status of cells has been ascribed to X chromosome activity, with two active X chromosomes generally only observed in undifferentiated or poorly differentiated cells. Recently, several studies have indicated that the reactivation of an inactive X chromosome or X chromosome multiplication correlates with the development of malignancy; however, this concept is still controversial. This review sought to shed light on the role of the X chromosome in cancer development. In particular, there is a need for further exploration of the expression patterns of X-linked genes in cancer cells, especially those in head and neck squamous cell carcinoma (HNSCC), in order to identify different prognostic subpopulations with distinct clinical implications. This article proposes a functional relationship between the loss of the Barr body and the disproportional expression of X-linked genes in HNSCC development.

The high morbidity and mortality associated with oral cancer has necessitated the exploration of newer diagnostic and prognostic biomarkers. In recent decades, targeting immune landscape has emerged as a newer approach as aggressive tumor biology and therapy resistance are influenced by the interplay between tumor and immune cells. A reciprocal association between chronic inflammation and carcinogenesis is well established and tumor infiltrating lymphocytes (TILs) represent inflammatory milieu of tumor microenvironment (TME). The varied T-cell phenotypes in different stages of cancer influence the prognostic and predictive response of the patients. Along with the conventional treatment options, Immunotherapy has evolved as a suitable alterative for oral carcinoma patients especially with recurrent and metastatic disease (R/M) but response is still unpredictable. Tumor microenvironment (TME) plays a key role to either lessen or boost up immune responses. There is an urgent need for extensive studies to be undertaken to better understand how tumor cells escape immune surveillance and resist immune attack. This review is an attempt to elucidate the concept of immune infiltrate in oral squamous cell carcinoma (OSCC) and thus, understanding the role of immunoscore as an adjunct to TNM staging to guide patient treatment.