We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula. We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming. We reveal sporadic contacts between Iberia and North Africa by~2500 BCE and, by~2000 BCE, the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with Steppe ancestry. We show that, in the Iron Age, Steppe ancestry had spread not only into Indo-European-speaking regions but also into non-Indo-European-speaking ones, and we reveal that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia. Additionally, we document how, beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean.

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Cyclin D1 promotes cell cycle progression during G1 phase, a key event in G1-S transition. The protein is encoded by gene CCND1, located in chromosomal band 11q13. Cyclin D1 plays key roles in cell biology, including cell proliferation and growth regulation, mitochondrial activity modulation, DNA repair, and cell migration control. CCND1 gene and its protein cyclin D1 are frequently altered by different molecular mechanisms, including amplification, chromosomal translocations, mutations, and activation of the pathways involved in cyclin D1 expression, alterations which appear to be essential in the development of human cancers, including oral carcinoma. This is the first published review of the specific features of cyclin D1 overexpression in oral oncogenesis. Starting with the physiological regulation of cyclin D1, there is an evaluation of its functions, overexpression mechanisms, and the implications of the oncogenic activation of CCND1/cyclin D1 in oral squamous cell carcinoma. The potential diagnostic and prognostic value of cyclin D1 is reviewed. The influence of CCND1/cyclin D1 on tumor size and clinical stage is reported, and an update is provided on the utilization of cyclin D1 as therapeutic target and on the combination of cyclin D1 inhibitors with cytotoxic agents. Future research lines in this field are also proposed.

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The objective was to evaluate current evidence on the prevalence and risk of oral cancer and potentially malignant oral disorders among patients with diabetes mellitus. We searched PubMed, Embase, Web of Science, and Scopus for observational studies published before November 2019. We evaluated the study quality using GRADE, QUIPS, and a specific method for systematic reviews addressing prevalence questions. Meta‐analyses were conducted, and heterogeneity and publication bias were examined. A total of 1,489 studies were found, 116 analyzed in full text, 52 included in qualitative synthesis and 49 meta‐analyzed. Pooled prevalence (PP) of oral cancer in patients with diabetic was 0.25% (95% CI = 0.15–0.39)—250 per 100,000 patients with diabetes mellitus —with a greater chance of oral cancer among patients with diabetes mellitus (OR = 1.41 [95% CI = 1.10–1.81], p = .007). Patients with oral cancer and diabetes mellitus had a higher mortality than controls (HR = 2.09 [95%CI = 1.36–3.22], p = .001). Leukoplakia had a PP = 2.49% (95% CI = 1.14–4.29)—2,490 per 100,000 patients with diabetes mellitus —(OR = 4.34 [95% CI = 1.14–16.55], p = .03). A PP of 2.72 (95% CI = 1.64–4.02) was obtained for oral lichen planus among patients with diabetic —2,720 per 100,000 patients with diabetes mellitus (OR = 1.87 [95% CI = 1.37–2.57], p < .001). A low PP was estimated for erythroplakia (0.02%[95%CI = 0.00–0.12]—20 per 100,000 patients with diabetes mellitus. In conclusion, patients with diabetes mellitus have a higher prevalence and greater chance of oral cancer and OPMD development in comparison with non‐diabetic patients. In addition, patients with oral cancer suffering from diabetes mellitus have a higher mortality compared to non‐diabetic patients with oral cancer.

Objectives: We present a critical review of the papers published in the international scientific literature on malignant transformation of oral lichen planus (OLP). Our aim is to report the most realistic estimate of the proportion of OLP cases with malignant transformation based on the highest quality of evidence. Materials and Methods:Following a literature search, we selected 89 papers that were published on this topic until November 2020. We applied to these papers an adaptation of the methodological quality criteria of the QUIPS tool and we ordered all of them according to their methodological quality. The papers that were in the upper quartile of methodological quality (10 papers) were selected and analyzed. Results:The pooled proportion (expressed as percentage) of malignant transformation of OLP reported in these high methodological quality papers was 2.28% (95% confidence intervals = 1.49-3.20). Conclusions:We observe that the proportion of malignancy is higher in research carried out under strict methodological quality criteria. In this critical review, we propose criteria for conducting follow-up studies on OLP to report on malignant transformation under strict quality standards.

Cortactin is a protein encoded by the CTTN gene, localized on chromosome band 11q13. As a result of the amplification of this band, an important event in oral carcinogenesis, CTTN is also usually amplified, promoting the frequent overexpression of cortactin. Cortactin enhances cell migration in oral cancer, playing a key role in the regulation of filamentous actin and of protrusive structures (invadopodia and lamellipodia) on the cell membrane that are necessary for the acquisition of a migratory phenotype. We also analyze a series of emerging functions that cortactin may exert in oral cancer (cell proliferation, angiogenesis, regulation of exosomes, and interactions with the tumor microenvironment). We review its molecular structure, its most important interactions (with Src, Arp2/3 complex, and SH3-binding partners), the regulation of its functions, and its specific oncogenic role in oral cancer. We explore the mechanisms of its overexpression in cancer, mainly related to genetic amplification. We analyze the prognostic implications of the oncogenic activation of cortactin in potentially malignant disorders and in head and neck cancer, where it appears to be relevant in the development of lymph node metastasis. Finally, we discuss its usefulness as a therapeutic target and suggest future research lines.

Objectives:To investigate the available evidence on the malignant transformation (MT) of oral proliferative verrucous leukoplakia (PVL). Material and Methods:We searched six main electronic and three grey literature databases in a two-phase process. Cohort studies investigating MT of PVL were eligible for inclusion. The risk of bias (RoB) was assessed using a specific tool developed by the Joanna Briggs Institute. Proportion meta-analyses were performed using a random-effects model. Results:Study selection resulted in the inclusion of 17 studies. The pooled proportion of MT was 43.87% (95% CI = 31.93-56.13). Females (64.02%, 95% CI = 54.87-72.75) were more affected by PVL than males (35.98%, 95% CI = 27.25-45.13). Gingiva (39.6%) and buccal mucosa (21.6%) were the most frequent PVL sites. No conclusive results were found between MT and sex or age distribution, tobacco, or alcohol consumption. Gingiva was the most common site for MT (39.9%), and the most frequent histopathological subtype was conventional squamous cell carcinoma (62.1%). Four studies were classified as low, nine as moderate, and four as high RoB. Conclusion:The MT pooled proportion was 43.87%. Among OPMDs, PVL has the highest risk to transform to malignancy. Development and agreement on diagnostic criteria for PVL would reduce the heterogeneity among future studies.