Ultrasensitive detection of tumor-specific mutations in saliva of patients with oral cavity squamous cell carcinoma

Ashwini Shanmugam, Arun K. Hariharan, Rifat Hasina, Jayalakshmi R. Nair, Shanmukh Katragadda, Sivaraj Irusappan, Aarthi Ravichandran, Vamsi Veeramachaneni, Radhakrishna Bettadapura, Muddasir Bhati, Veena Ramaswamy, Vishal U.S. Rao, Ritvi K. Bagadia, Ashwini Manjunath, N. M.L. Manjunath, Monica Charlotte Solomon, Shiuli Maji, Urvashi Bahadur, Chetan Bettegowda, Nickolas PapadopoulosMark W. Lingen, Ramesh Hariharan, Vaijayanti Gupta, Nishant Agrawal, Evgeny Izumchenko

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Background: Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck malignancy. Although the survival rate of patients with advanced-stage disease remains approximately 20% to 60%, when detected at an early stage, the survival rate approaches 80%, posing a pressing need for a well validated profiling method to assess patients who have a high risk of developing OCSCC. Tumor DNA detection in saliva may provide a robust biomarker platform that overcomes the limitations of current diagnostic tests. However, there is no routine saliva-based screening method for patients with OCSCC. Methods: The authors designed a custom next-generation sequencing panel with unique molecular identifiers that covers coding regions of 7 frequently mutated genes in OCSCC and applied it on DNA extracted from 121 treatment-naive OCSCC tumors and matched preoperative saliva specimens. Results: By using stringent variant-calling criteria, mutations were detected in 106 tumors, consistent with a predicted detection rate ≥88%. Moreover, mutations identified in primary malignancies were also detected in 93% of saliva samples. To ensure that variants are not errors resulting in false-positive calls, a multistep analytical validation of this approach was performed: 1) re-sequencing of 46 saliva samples confirmed 88% of somatic variants; 2) no functionally relevant mutations were detected in saliva samples from 11 healthy individuals without a history of tobacco or alcohol; and 3) using a panel of 7 synthetic loci across 8 sequencing runs, it was confirmed that the platform developed is reproducible and provides sensitivity on par with droplet digital polymerase chain reaction. Conclusions: The current data highlight the feasibility of somatic mutation identification in driver genes in saliva collected at the time of OCSCC diagnosis.

Original languageEnglish
Pages (from-to)1576 - 1589
Number of pages14
Issue number10
Publication statusPublished - 15-05-2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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