A team of Indian scientists has discovered oral cancer-causing driver gene mutations in women patients in southern parts of the country.
The scientists from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru and the BRIC-National Institute of Biomedical Genomics (NIBMG), Kalyani, in collaboration with clinicians from Sri Devraj Urs Academy of Higher Education and Research (SDUAHER), Kolar, conducted a female-centric study on oral cancer in India with a unique tobacco chewing habit.
This study led by Professor Tapas K Kundu, JNCASR, Bengaluru aimed to understand what makes cancers in women unique, how the disease manifests and progresses in female patients and how we can treat them better.
The team also used artificial intelligence (deep learning) to digitally analyse tumour tissues. This revealed two distinct groups of female patients, each with a different immune response in their tumours.
India carries one of the world’s heaviest burdens of oral cancer with alarmingly high rates witnessed among women in certain regions, especially in southern and northeast India, due to the widespread habit of chewing tobacco-infused betel quid, gutka, and related products.
While the disease is widely studied in men, oral cancer in women has often remained under the radar.
The study was performed on paired tumour and blood samples from female OSCC-GB patients with a unique regional tobacco-chewing habit (Kaddipudi), commonly observed among women in the Kolar district of Karnataka.
Analysis of this women-centric cohort has revealed a unique driver mutation implicated in oral tumorigenesis.
This investigation, published in the Clinical and Translational Medicine Journal, was specifically designed to uncover the biological underpinnings of the disproportionately aggressive, highly recurrent, and life-threatening forms of oral cancer that affect Indian women.
Using cutting-edge whole-exome sequencing, the researchers identified ten key genes with significant mutations in the female oral cancer cohort from Kolar, Karnataka.
Although two of the major genes known as CASP8 and TP53 were found to be highly mutated in these patients, uniquely, CASP8 seems to be the driver mutation (cancer-causing), which is quite different compared to previously studied mutations in oral cancer patients (largely men).
The findings suggest that co-occurring TP53 and CASP8 mutations confer a markedly aggressive and lethal phenotype in oral cancer.
The team is now focused on delineating the molecular mechanisms of oncogenesis driven by this novel driver mutation within the background of TP53 alterations for the next phase of the research.
Despite the magnitude of the burden, participation in screening remains notably low. According to a separate study published in ScienceDirect in February 2025, nationally, only 1.2 per cent of men and 0.9 per cent of women undergo screening, with substantial variation reported across States and Union Territories.
Dr Ayushi Jain and Dr Shalini Gupta from King George Medical University, Lucknow, and authors of the study, ‘Do the recorded cases of oral cancer correspond to the actual numbers in India: The necessity of properly designed screening and surveying initiatives,’ attribute this gap to limited awareness, inadequate early-detection programmes, and uneven access to healthcare infrastructure, particularly in rural and underserved regions.
The prevalence of tobacco use continues to be a dominant risk factor. Nearly 29 per cent of Indian adults consume tobacco, many beginning in adolescence or early adulthood. Involuntary use of smokeless tobacco, often embedded within traditional dental-care products, remains a largely unregulated concern, said the study.
Public-health studies indicate that mass or targeted high-risk screening conducted once every ten years has the potential to substantially reduce mortality associated with oral cancers. However, the lack of trained personnel, limited community outreach, and minimal utilisation of preventive health services have slowed progress.
The health researchers noted that the disparity between documented cases and the likely actual burden underscores the need for wider and more systematic surveillance. Screening programmes, they argue, must expand beyond symptomatic or high-risk individuals to include younger populations under 30 years — an age group where early tobacco exposure is increasingly common.
The way forward, the experts suggested, lies in a multi-pronged approach. Telemedicine-enabled assessment, door-to-door awareness activities, and community-based screening initiatives could strengthen early detection. The involvement of grassroots health workers, including ASHA personnel and trained volunteers, is expected to play a crucial role in bridging access gaps, improving participation, and facilitating timely referral to tertiary facilities, said the study.
