Project at a glance

  • Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world and is the leading cancer among men in India.
  • Chewing betel-quid—comprising betel leaf (Piper betle), areca nut (Areca catechu), and slaked lime (predominantly calcium hydroxide), with or without tobacco—a tradition popular in India, is a major cause of such cancers in the subcontinent.
  • Early-stage OCSCC tends to have an overall better prognosis; patients would benefit from biomarker-based tools that can aid in early diagnosis and intervention.
  • Recently developed highly sensitive technologies have been successful in detecting and quantifying released tumor DNA as a biomarker in saliva.
  • Genomic alterations have been definitively shown to be the molecular signatures of oral cancer.
  • Saliva is preferentially enriched for released tumor DNA from oral cavity cancers, which makes it ideal for screening of OCSCC or its precursors.

Why this study

Oral cancer is the most common amongst all head and neck squamous cell cancers (HNSCC)—the third most frequently occurring cancer in India, representing approximately 20 percent of all cancers. It is the leading cancer among men in India and the fifth most frequently occurring cancer in women. In most cases, the cancer is detected at advanced stages and treatment at stage III and IV is challenging, with abysmal survival outcomes and poor quality of life.

A proposed solution to this burden is early diagnosis. OCSCC, like other cancers, is characterized by genetic mutations that are specific to the tumor cells. These somatic alterations (or tumor DNA) have been shown—by oncologists at UChicago Medicine and India—to be detected in the saliva of patients, including those with early-stage OCSCC.

This project’s long-term goal is to establish a non-invasive molecular saliva screening and diagnostic test that is capable of identifying and clinically stratifying pre-cancerous and early-stage oral cancer. After completion of this proposed observational study, the next phase will be to conduct a prospective interventional study in high-risk patients.

The ultimate endpoints will be disease-free survival, overall survival, quality of life, and medical costs in patients who are randomized to being screened by the salivary DNA test versus diagnosis per current standard of care. The salivary DNA test would amount to significant lead time in the diagnosis of oral cancer and improved survival and quality of life with significantly lower costs.

Approach

This project is piloting a novel approach to diagnosing Oral Cavity Squamous Cell Carcinoma (OCSCC), which is a leading cancer and cause of death in India. Most cases of OCSCC are diagnosed at an advanced stage with poor survival and quality of life outcomes.

Evidence suggests that this form of oral cancer can be diagnosed early and treated as localized tumors, leading to better overall prognosis and dramatically lower treatment costs, which would reduce mounting financial strains on the Indian healthcare system.

The researchers will develop a salivary DNA kit for simple, low-cost screening that could be used in high-risk patients to identify pre-cancerous and early stage lesions, which can be addressed with definitive interventions. The tool could directly inform India’s public health initiatives focused on oral cancer and eventually, benefit at-risk populations around the globe.

The step by step process is to:

  • Identify a biomarker gene panel consisting of the most commonly mutated genes in OCSCC
  • Collect saliva from 150 OCSCC patients (of all stages) who are receiving treatment at several hospitals in India
  • Extract released tumor DNA from saliva samples
  • Sequence tumor DNA for the biomarker gene panel to determine presence of mutations
  • Evaluate the diagnostic and prognostic accuracy of released tumor DNA versus conventional diagnosis via histopathology