Gingivo-buccal cancers are differentSeptember 14, 2018
Dr Krishnakumar Thankappan
Squamous cell carcinoma of the oral cavity accounts for about 3.8% of all cancers worldwide. While it is the sixth commonest cancer in the
world, it is one of the most common entities in the Indian subcontinent and Asia.
The presence of multiple sub-sites within the mouth is a peculiarity. Though these sub-sites are anatomically placed together, the cancers in these areas behave differently. Oral tongue and buccal mucosa are the two commonly involved sub-sites in cancer.
Buccal cancers include those arising from the buccal mucosa and those afflicting upper or lower gingivobuccal areas. Oral tongue is the commonest site for mouth cancers in western literature, whereas in Asian countries, buccal cancers are more prevalent.
So much so that it is the most
common type of cancer found in men in India.
Anatomically, the sub-site is different in that it is closely related to the bony boundaries of the oral cavity, the mandible and the maxillary alveolus. It has a thin, layered structure compared to the muscular tongue. Being in contact with the muscles of mastication, the buccal mucosa sub-site has a critical relationship with the masticator space and the infratemporal fossa. Advanced tumours also tend to invade the skin.
Though squamous cell carcinoma is the most common pathology among the cancers of oral cavity, they seem to have a diverse etiology. The use of smokeless tobacco, betel quid chewing and areca nut preparations are causative in buccal mucosal cancers, while smoking and alcohol seem to be the reason for tongue cancers. Studies from India and western literature have noted that buccal cancer patients are older and present for treatment at more advanced stages. Oral submucous fibrosis — a unique, chronic, insidious disease affecting the oral cavity — creates a predisposition to buccal cancers. It is characterized by varying intensity of fibro-elastic changes resulting in progressive trismus. It has been suggested that chewing of areca nut and other factors like nutritional deficiency contributes to
the pathogenesis of this condition. Patients with this condition are at
least nineteen times more at risk to develop oral cancer than healthy individuals.
Buccal tumours of the Indian subcontinent and other south-east Asian countries may be different from the western disease in the spectrum of molecular changes. An earlier study has shown the involvement of the ras oncogenes, like that of loss of heterozygosity (H-ras) and amplification (K and N-ras are more common in the eastern tumours). Similarly, p53 mutations are infrequent in the Indian subcontinent tumours. Other changes like overexpression of Cyclin D1, high accumulation of STAT-3 are also reported. The Indian project team of the International Cancer Genome Consortium have reported many pathways that are enriched for genomic alterations specific to gingiva-buccal cancers. Exome sequencing and other data showed (a) significantly and recurrently mutated genes (b) new genes with recurrent amplifications or homozygous deletions (c) existence of molecular subtypes with distinctive mutational profiles (d) high proportion of C>G transversions (e) enrichment of alterations of pathways specific to gingivo-buccal oral cancer. Recurrently mutated genes were validated using the data from an independent set of 30 gingivo-buccal patients.
Gingivo-buccal cancers have less propensity to metastasize. While 70% of the cancers of the tongue tend to metastasize, only less than half of the buccal cancers are seen to do so.
Staging and implications
The eighth edition of the American Joint Committee on Cancer (AJCC) has introduced significant changes in this area, mainly based on the evidence
from the western literature that have more relevance to those countries. The staging system applies more to tongue cancers.
Advanced cancers of the oral cavity (tumour stage T4) are subdivided into T4a and T4b, with treatment and prognostic implications. T4b cancers are generally very advanced tumours which are often treated with palliative intent only. But there is recent evidence, including studies from India, which show that a sub-group of these patients with limited spread (infra-notch) may do better. These cancers may be considered for down-staging to T4a, based on data.
Though the series by Gupta et al in their research article titled “Do we need a different staging system for tongue and gingivobuccal complex squamous cell cancers?”, published in Oral Oncology concluded that there is no need for a separate staging system, recent reports from India indicate the need for one. Compartmental resection of buccal cancers, a newer concept in the surgical management of buccal cancers, ensures better clearance of the disease and is postulated to result in better oncological outcomes.
Gupta et al reported that overall survival for gingivo-buccal cancers in their series of about 1500 oral cavity cancers was significantly poorer than oral tongue cancers. Another study on a cohort of advanced gingivo-buccal cancers, led by Dr KA Pathak, found that patients with pT3/T4 disease and margin-positive disease had poorer outcomes. An analysis of the Surveillance, Epidemiology and End Results (SEER) database showed a 5- year survival rate of 65% for tongue cancer and 59.1% for cancers of the gum and other parts of the mouth (excluding lips, oropharynx, and tonsil.) Patients with carcinoma of the gingivo-buccal sulcus, palate and lip had significantly better locoregional control (68 vs 57%, p=0.005) and disease-free survival (64% vs 52%, p=0.001) compared to patients with squamous carcinoma of the tongue and floor of mouth, according to a Mumbai study.
In short, gingivo-buccal cancers seem to be a different disease in etiology, clinicopathology and outcomes. Early findings from cancer genome studies open new avenues for biological characterization and exploration of new treatment strategies. There is a need for a separate staging system to prognosticate, treat and report the outcomes of these tumours.