Khariwala's Research Program
Area of Focus
My research focuses primarily on the metabolism of tobacco carcinogens to better understand this risk and susceptibility of oral/head and neck cancer in smokers, as well as biomarkers and outcomes in head and neck cancer. Dr. Khariwala's research has been funded by multiple grants including; K23DE023572, 1RO1-TW010651, and R01-CA263084.
High-resolution Mass Spectrometric Profile Analysis of Carcinogen-DNA Adducts in Oral Cells of Cigarette Smokers and Squamous Cell Carcinoma of the Head and Neck
Profile analysis of carcinogen-DNA adducts in oral cells of cigarette smokers and SCC of the H&N
This is an observational study to analyze the oral cells of individuals who are susceptible to squamous cell carcinoma of the head and neck (HNSCC). We hope that in the future, for individuals with such a susceptibility who are unable to quit smoking, we would recommend aggressive lifestyle and monitoring interventions to prevent this disfiguring and often fatal cancer.
Head & Neck Cancer Data Repository
The primary aim of this project is to establish and maintain a database to collect routine clinical data in a systematic and cost-efficient manner from the medical records of persons diagnosed with cancers of the head and neck and who receive or have received care at the University of Minnesota.
Outcomes for Metastatic H&N SCC
Despite the abundance of literature investigating the incidence, risk factors, diagnosis, and treatment of metastatic Head and Neck (H&N) Squamous Cell Carcinoma (SCC), a survival analysis of patients grouped by the site of metastasis has not been reported. Our clinical experience suggests that not all sites of metastasis are equal with regard to prognosis. Defining this would be of great benefit to the patient when considering end-of-life options including local therapy or palliative care.
The current trial seeks to:
- Analyze Survival of patients with H&N SCC based on site(s) of metastatic disease
- Compare survival of patients who received therapy after diagnosis of metastases to those who did not pursue further treatment
- Delineate terminal pathways for patients with H&N SCC based on the site of metastatic or advanced local disease
Analytical Capacity Building for the Study of Tobacco Carcinogen Exposures in India:
This was a collaborative study with researchers from the Advanced Centre for Treatment, Research, and Education in Cancer (ACTREC) in Mumbi India to examine the relationship between NNN and NNK levels in smokeless tobacco products and the levels of corresponding biomarkers in users of these projects.
NIkam SS, Gota V, Gupta PC, Puntambekar N, Singh A, Chaturvedi P, Villalta PW, Hatsukami DK, Ahluwalia JS, Basu S, Khariwala SS, Stepanov IS. Variability in addictive and carcinogenic potential of smokeless tobacco products marketed in Mumbai, India: a surveillance study. Lancet Global Health SE Asia. 2024. 29: 100457. https://doi.org/10. 1016/j.lansea.2024. 100457
Van Heest T, Rubin N, Khariwala SS. Persistent tobacco use following treatment for head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2022;148(7):597-603. doi: 10.1001/ jamaoto.2022.0810.
Khariwala SS, Nichols CM, Stull C, Ross MW. Development of A Scoring System to Assess Smartphone Photographic Oropharyngeal Screening. Annals of Otol Head and Neck Surg. 2024;3(2):1-4.
Ross MW, Khariwala SS, Bennis SL, Zoschke IN, Rosser BS, Nyitray AG, et al. Using Low-cost Videoscopes to Obtain Accurate Video “Oral Selfies” as Screening for HPV-associated Oropharyngeal Cancer: A New Screening Technology? Cancer Screen Prev. 2024;3(2):125-129. doi: 10.14218/CSP.2024.00005.
Nikam SS, Gurjar M, Singhavi H, Patil A, Singh A, Villalta P, Chaturvedi P, Khariwala SS, Gota V, Stepanov I. Simultaneous analysis of urinary total 4‑(methylnitrosamin o)‑1‑(3‑pyridyl)‑1‑butanol, N′‑nitrosonornicotine, and cotinine by liquid chromatography‑tandem mass‑spectrometry. Scientific Reports. 2021. 11:20007. https://doi.org/10.1038/
View more of Dr. Khariwala's publications: https://pubmed.ncbi.nlm.nih.gov/?term=Khariwala+SS
Project Spotlight
Profile Analysis of 12 Oral Cell DNA Adducts in Squamous Cell Carcinoma of the Head & Neck
Squamous cell carcinoma of the head and neck (HNSCC) is a devastating, frequently disfiguring, and often fatal disease, expected to affect more than 53,000 people in the U.S. in 2020 and kill more than 10,000. Prevention of this terrible disease is critical. Cigarette smoking, alcohol consumption, and human papilloma virus (HPV) are well established major causes of HNSCC; only smoking and alcohol consumption are considered here. Cigarette smoking and alcoholic drinks are sources of multiple DNA adducts that are critical in the carcinogenic process. This proposal will establish a liquid chromatography-
1. Develop an LC-NSI-HRMS/MS Profile Analysis Method
Develop a method for quantitation of 12 important representative carcinogens and toxicants - DNA adducts in human oral cells and tissue. The adducts are derived from various carcinogens and DNA reactive compounds in cigarette smoke and alcoholic beverages.
2. Apply the Profile Analysis to Oral Cells from Healthy Individuals
a) 100 non-smokers who are nondrinkers or light drinkers;
b) 100 cigarette smokers who are non-drinkers or light drinkers
c) 100 cigarette smokers who are moderate or heavy drinkers
Comparisons of adduct levels in groups a and b will identify adducts enhanced by cigarette smoking while comparisons of groups b and c will identify adducts that are enhanced by the combination of smoking and moderate or heavy drinking.
3. Longitudinal Study
Test the longitudinal stability of the oral cell DNA adduct profile analysis over a 6 month period in 50 smokers who are non-drinkers or light drinkers.
4. Analyze & Compare
A) Determine the DNA adduct profile in oral cells collected from 75 smokers with HNSCC and compare to that in 200 smokers without HNSCC recruited in Specific Aim 2 with the goal of identifying an adduct profile that is characteristic of HNSCC incidence.
B) Compare the oral cell DNA adduct profile from part A of this aim to that in tissue, both normal and tumor, in a subset of 60 patients from part A who undergo surgery, to determine whether oral cell DNA adduct patterns are consistent with those in tissue.
Project Results
Our results will potentially identify individuals who are susceptible to HNSCC but are unable to quit smoking. Once identified, aggressive lifestyle and monitoring interventions in these subjects such as oral examinations 2-4 times per year can be initiated for prevention or early detection of this disfiguring and often fatal cancer.
Meet the Team
See the Science: Research Photos
Dr. Khariwala's research team in Mumbai, India.
