Molecular mechanisms of head and neck cancer

Abstract

Background-With a global incidence rank of eight and a significant portion of head and neck malignancies (~90%), oral squamous cell carcinoma (OSCC) poses a major health risk and is one of the leading cause of mortality in developing nations [1]. Distribution of the incidence of OSCC varies across the world with south-central Asia and Africa leading, followed by eastern and central Europe, and to a lesser extent Australia, Japan, and the United States. Over the past few years there has been a drastic increase in the incidence of oral cancer in most parts of the world [2]. In the United States alone, with about 17 new cases/100,000, oral cancer is the fifth most common and sixth leading cause of cancer-related mortality per year [3].While men tend to have a higher incidence of OSCC (6.6/100,000) compared to women (2.9/100,000), there is an equal mortality rate between the sexes (50%).

Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

“…RHEB overexpression could also underlie PI3K/AKT-independent mTORC1 activation in human cancers, previously identified in a subgroup from a large HN cancer cohort (39). Carcinogen exposure via smoking is a known risk factor for HN cancer (40), however cooperation between RHEB and smoke carcinogens has not been reported. Here, Rheb potently sensitized transgenic mice to a single dose of the DMBA producing multistage squamous carcinogenesis accompanied by coordinate induction of ERK1/2.…”

Cervical lymph node metastases of squamous cell carcinoma from an unknown primary site: a favourable prognosis subset of patients with CUP

“…Common genetic alterations in head/neck cancer of known primary (incidence 30-60%), such as COX2 activation, EGFR overexpression and inactivation of the tumour suppressors p16, p21, p53 and pRB, have not been investigated in SQCCUP. Overexpression of MET and activation of cyclin D1, Ras and AKT occur in one third to one quarter of head/neck cancers, resulting in increased cellular proliferation, apoptosis inhibition, invasion and metastasis [8]. Angiogenesis is particularly active in head/neck cancer and microvessel density and VEGF expression by immunohistochemistry or PCR have been associated with aggressive disease course and poor outcome [9].…”

“…In addition, based on the metastatic lymph node level, several probable sites of the primary tumours can be predicted, i.e., (a) if submandibular nodes (level I) are involved the primary site could be in the fl oor of the mouth, lips and anterior tongue; (b) if jugulodigastric or upper jugular nodes (level II) are affected, search for a primary tumour in epipharynx, base of the tongue, tonsils, nasopharynx and larynx, (c) if middle and lower jugular nodes (levels III and IV) are involved, the most likely primaries are located in hypopharynx or larynx; and (d) if supraclavicular nodes (level V) are the metastatic sites, the possible primary tumours could be derived from the lungs, thyroid, breast, gastrointestinal or genitourinary system [7,8] (Table 1). The most commonly involved level is level II (30-50%), followed by levels I and III (10-20%) and levels IV and V (5-10%).…”

Loss of TGF-β signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation

“…Tobacco, alcohol consumption, and human papillomavirus (HPV) are the major risk factors associated with the development of HNSCC (Licitra et al ., 2006; Curado et al ., 2009). These risk factors, together with genetic susceptibility, result in the accumulation of multiple genetic and epigenetic alterations in a multistep process of cancer development (Deshpande et al ., 2008). In addition, the tumor microenvironment also contributes significantly to head and neck carcinogenesis (Yang et al ., 2010).…”