Squamous cell carcinomas
2025-12-04 Paola Dal Cin, PhD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Keywords
Oral squamous cell carcinoma,verrucous carcinoma , carcinoma cuniculatum ,premalignnay conditions, tumor behavior. betel nut, poor oral hygieneClassification
Definition
The oral cavity is the most common location in the head and neck for both verrucous carcinoma (VC) and carcinoma cuniculatum (CC) which have distinct clinical and histologic features from conventional squamous cell carcinoma (SCC). 1 There is no a strong association with HPV in both lesions , as well as in oral squamous cell carcinoma (OSCC). 2 In general the etiology of these lesions is primarily use of oral smokeless (chewing) tobacco in any form, of betel quid without tobacco and of areca nut in some geographic regions. 3 In 20% of cases VC may be a precursor to conventional OSCC. However, VC lacked any of the classical OSCC patterns such as gain of 3q and loss of 3p and demonstrated considerably fewer genomic rearrangements compared to the OSCC cohort. 4
Genetic and epigenetic changes, alterations in signaling pathways, contribute to the mutational landscape that is associated in the resistance to therapy and impaired prognosis in OSCC. 5,6 Somatic mutations in several genes in oral squamous cell carcinoma (OSCC) have been identified including , among others, TP53,NOTCH1,FAT1,KMT2D, CASP8, AJUBA, NSD1, CNQ4 and TGFBR2 as early events , and CDKN2A as late event. Amplifications were also seen with the most frequent been FGF3, FGF19, and CCND1. 5,7-9
Betel quid (BQ) chewing is a profound risk for oral squamous cell carcinoma (OSCC) in Southeast Asia, similar mutations were found, with some local variations in both percentage and new additional mutations. 10
Using a liquid biopsy technique, especially cell-free DNA (cfDNA) analysis, TTN, PLEC, SYNE1, and USH2A were the most frequently mutated in OSCC, while RORC,SLC49A3 and MBL2 were significantly associated with metastatic disease. 11
Oral squamous cell carcinoma (OSCC) in non-smoking and non-drinking (NSND) affects younger individuals, with high proportion of female. The exact cause of OSCC in younger, NSND patients remains unknown, although there has been much progress to genomically characterize NSND OSCC as distinctly different from the traditional OSCC. 12
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 38689630 | 2024 | Classificatory updates in verrucous and cuniculatum carcinomas: Insights from the 5(th) edition of WHO-IARC head and neck tumor classification. | Silveira FM et al |
| 2 | 36851665 | 2023 | The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma. | Katirachi SK et al |
| 3 | 25411778 | 2014 | Systematic review and meta-analysis of association of smokeless tobacco and of betel quid without tobacco with incidence of oral cancer in South Asia and the Pacific. | Gupta B et al |
| 4 | 26014678 | 2015 | A novel genomic signature reclassifies an oral cancer subtype. | Samman M et al |
| 5 | 35047986 | 2020 | Major Molecular Signaling Pathways in Oral Cancer Associated With Therapeutic Resistance. | Usman S et al |
| 6 | 39000073 | 2024 | New Insights for an Advanced Understanding of the Molecular Mechanisms in Oral Squamous Cell Carcinoma. | Caruntu A et al |
| 7 | 31542510 | 2020 | Translational genomics and recent advances in oral squamous cell carcinoma. | Chai AWY et al |
| 8 | 33993060 | 2021 | NOTCH1 mutations as prognostic marker in oral squamous cell carcinoma. | Wu-Chou YH et al |
| 9 | 39324009 | 2024 | Genomic alterations in the stepwise progression from normal mucosa to metastasizing oral squamous cell carcinoma. | Jensen JM et al |
| 10 | 36575633 | 2022 | Systemic and Local Effects Among Patients With Betel Quid-Related Oral Cancer. | Chuang HC et al |
| 11 | 37373553 | 2023 | Identification of Somatic Mutations in Plasma Cell-Free DNA from Patients with Metastatic Oral Squamous Cell Carcinoma. | Lin LH et al |
| 12 | 37633348 | 2023 | Oral cavity cancer in young, non-smoking, and non-drinking patients: A contemporary review. | Tran Q et al |
Citation
Paola Dal Cin, PhD
Squamous cell carcinomas
Atlas Genet Cytogenet Oncol Haematol. 2025-12-04
Online version: http://atlasgeneticsoncology.org/solid-tumor/209357/squamous-cell-carcinomas
