Hallmarks of Cancer Applied to Oral and Oropharyngeal Carcinogenesis: A Scoping Review of the Evidence Gaps Found in Published Systematic Reviews

Abstract

In 2000 and 2011, Hanahan and Weinberg published two papers in which they defined the characteristics that cells must fulfil in order to be considered neoplastic cells in all types of tumours that affect humans, which the authors called “hallmarks of cancer”. These papers have represented a milestone in our understanding of the biology of many types of cancers and have made it possible to reach high levels of scientific evidence in relation to the prognostic impact that these hallmarks have on different tumour types. However, to date, there is no study that globally analyses evidence-based knowledge on the importance of these hallmarks in oral and oropharyngeal squamous cell carcinomas. For this reason, we set out to conduct this scoping review of systematic reviews with the aim of detecting evidence gaps in relation to the relevance of the cancer hallmarks proposed by Hanahan and Weinberg in oral and oropharyngeal cancer, and oral potentially malignant disorders, and to point out future lines of research in this field.

Hallmarks of Cancer Expression in Oral Lichen Planus: A Scoping Review of Systematic Reviews and Meta-Analyses

“…Among the molecular mechanisms most closely linked to the stimulation of epithelial proliferation are those exerted by the epidermal growth factor receptor (EGFR or ErbB) family and its ligands, the epidermal growth factors (EGF) [ 64 ]. The most relevant member of the EGFR family is ErbB2 because it is the most efficient in terms of stimulating proliferation [ 65 , 66 , 67 ].…”

“…However, there are published primary-level studies—case series—in which the overregulation of these receptors or CCND1/cyclin D1 in OLP has been analyzed [ 29 , 80 , 81 , 82 , 83 ], which could probably allow the performance of a systematic review and meta-analysis providing evidence-based information on this aspect. The activation of the pro-proliferative MAPK and PI3K/Akt pathways can also occur through the stimulation of Ras protein and its downstream targets [ 64 ]. The Ras oncogene is frequently mutated in human melanomas [ 84 , 85 ] and is one of the most frequently altered oncogenes in OSCC [ 86 ], especially with regard to HRas mutations [ 87 , 88 ], leading to its constitutive activation with hyperproliferation.…”

“…All of this leads to the development of senescence [ 104 ]. The aforementioned induction of cell differentiation linked to the actions of p53 makes the cells resistant to reprogramming, thus preventing them from acquiring the characteristics of cancer stem cells [ 105 ]; all of this appears to be relevant to the exercise of p53 as a tumor suppressor protein [ 64 ]. There is no evidence in the form of systematic reviews and meta-analyses on the implications of p53 for OLP malignancy; neither is there evidence for its subsidiary proteins p21 and p16.…”

“…Tumor development obviously requires overcoming apoptotic mechanisms [ 123 , 124 ]. Tumor cells can overcome apoptosis by various pathways, although TP53 mutations, the overregulation of Bcl-2 and Bcl-xL, the underregulation of Bax and other proapoptotic [ 64 ] mechanisms are particularly noteworthy.…”

“…Human cells physiologically present a limited survival program—linked to a predetermined number of proliferative cycles—that aims to eliminate aging cells that will be replaced by progeny better equipped to fulfill the functions for which they were created, thus minimizing the risks of aging [ 64 ]. The main mechanism involved in this process is mediated by the shortening of telomeres, which are non-coding fragments of DNA consisting of hexanucleotide tandem repeats (TTAGGG), located at the ends of chromosomes, whose mission is to protect DNA [ 141 ].…”