Oral Cancer written out with a hand
By IHPL - May 5, 2021

Oral squamous cell carcinoma (OSCC) significantly trails behind other cancers in research funding and, as a result, in survival. Survival is worse in racially and socioeconomically disadvantaged groups. Completion of the human genome project in 2001 ushered in an era of personalized medicine. The hope was that genome-wide approaches would facilitate the development of highly effective biomarkers to determine risk in cancer patients. Some cancers have had significantly improved outcomes from substantial research funding to develop biomarkers for risk prediction.1,2 For example, commercially available genomic tests predict the risk of recurrence in breast cancer patients and are currently used to guide treatment decisions.3-5 These and other advances in breast cancer treatment fueled by biomarker research have resulted in improvement in survival over the past two decades, particularly in young women with metastatic disease.2

In contrast, OSCC survival has remained stagnant. OSCC research funding lags significantly behind that of other cancers. OSCC incidence is on the rise, affecting 400,000 people globally each year, with the largest increase in young patients.6 Aside from high mortality, OSCC patients suffer from significantly higher morbidity than other cancers, due to the cosmetic and functional deformities resulting from treatment that affect their ability to eat, taste, speak, and relate to others.7 In the U.S. alone, 30,000 people are diagnosed with OSCC annually, of which about half will die of their disease, accounting for approximately one death per hour.8 Socioeconomic and racial disparities are augmented in this particular cancer, with black patients and patients with lack of access to care suffering from delays in diagnosis that portend worse survival.9

OSCC survival also falls behind other head and neck cancer sub-sites. OSCC is a subset of head and neck cancers that is distinct from oropharyngeal SCC (OPSCC). The two diseases have divergent clinical behavior. More than 70% of newly-diagnosed OPSCC is caused by human papilloma virus (HPV) infection.10 HPV status serves as a reliable biomarker for survival. HPV-positive OPSCC has significantly better survival than HPV-negative disease. A concerted research effort and research funding support for clinical trials targeting HPV-positive OPSCC has improved the survival rate to as high as 90%.11,12 Conversely, HPV does not play a significant role in OSCC.13 Fifty percent  of newly diagnosed OSCC cases are early stage I or II.14 These early stage patients still have 40% risk of 5-year mortality. The largest increase in oral cancer incidence has been in young patients without smoking or drinking history.15,16 Unfortunately even these young patients have poor survival.

Due to disparate research funding, oral cancer research to develop novel treatments falls behind that of other cancers. The amount of governmental and foundation research funding for different cancers have little to do with how common the cancer is or how many people it kills. Rather, cancers surrounded by stigma receive significantly less funding. Unfortunately, oral cancer falls in this category, as it is falsely perceived to be a result of heavy tobacco and alcohol use. We know from recent epidemiologic studies that young patients without these traditional risk factors are still susceptible to developing oral cancer dying of the disease. There needs to be a focus on equalizing cancer research funding to address these disparities in survival, which are a direct result of lack of rigorous research that would lead to treatment advancements.


Author Bio:

Chi Viet, DDS, PhD, MD

Chi Viet, DDS, PhD, MD

Dr. Chi Viet is a surgeon scientist focused on head and neck cancer management. She serves as an Assistant Professor of Oral Maxillofacial Surgery at the School of Dentistry as well as the School of Medicine. Her extensive research experience and interests include head and neck carcinogenesis, neurobiological basis of symptoms faced by head and neck cancer patients, and epigenetic pathways of head and neck cancer.

References:

  1. O'Dowd A. Skin cancer is on the increase but incidence of lung cancer is falling. BMJ. 2007;335(7615):322.
  2. Guo F, Kuo YF, Shih YCT, Giordano SH, Berenson AB. Trends in breast cancer mortality by stage at diagnosis among young women in the United States. Cancer. 2018;124(17):3500-3509.
  3. van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530-536.
  4. Fan C, Oh DS, Wessels L, Weigelt B, Nuyten DS, Nobel AB, van't Veer LJ, Perou CM. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med. 2006;355(6):560-569.
  5. Ross JS, Hatzis C, Symmans WF, Pusztai L, Hortobagyi GN. Commercialized multigene predictors of clinical outcome for breast cancer. Oncologist. 2008;13(5):477-493.
  6. Gulland A. Oral cancer rates rise by two thirds. BMJ. 2016;355:i6369.
  7. Dhanuthai K, Rojanawatsirivej S, Thosaporn W, Kintarak S, Subarnbhesaj A, Darling M, Kryshtalskyj E, Chiang CP, Shin HI, Choi SY, Lee SS, Aminishakib P. Oral cancer: A multicenter study. Medicina oral, patologia oral y cirugia bucal. 2018;23(1):e23-e29.
  8. Yoon AJ, Wang S, Kutler DI, Carvajal RD, Philipone E, Wang T, Peters SM, LaRoche D, Hernandez BY, McDowell BD, Stewart CR, Momen-Heravi F, Santella RM. MicroRNA-based risk scoring system to identify early-stage oral squamous cell carcinoma patients at high-risk for cancer-specific mortality. Head Neck. 2020;42(8):1699-1712.
  9. Yu AJ, Choi JS, Swanson MS, Kokot NC, Brown TN, Yan G, Sinha UK. Association of Race/Ethnicity, Stage, and Survival in Oral Cavity Squamous Cell Carcinoma: A SEER Study. OTO Open. 2019;3(4):2473974X19891126.
  10. Vigneswaran N, Williams MD. Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 2014;26(2):123-141.
  11. Dowthwaite SA, Franklin JH, Palma DA, Fung K, Yoo J, Nichols AC. The role of transoral robotic surgery in the management of oropharyngeal cancer: a review of the literature. ISRN Oncol. 2012;2012:945162.
  12. Viet CT, Dierks EJ, Cheng AC, Patel AA, Chang SC, Couey MA, Watters AL, Hoang T, Xiao HD, Crittenden MR, Leidner RS, Seung SK, Young KH, Bell RB. Transoral robotic surgery and neck dissection for HPV-positive oropharyngeal carcinoma: Importance of nodal count in survival. Oral Oncol. 2020;109:104770.
  13. Bragelmann J, Dagogo-Jack I, El Dinali M, Stricker T, Brown CD, Zuo Z, Khattri A, Keck M, McNerney ME, Longnecker R, Bieging K, Kocherginsky M, Alexander K, Salgia R, Lingen MW, Vokes EE, White KP, Cohen EE, Seiwert TY. Oral cavity tumors in younger patients show a poor prognosis and do not contain viral RNA. Oral Oncol. 2013;49(6):525-533.
  14. Lydiatt WM, Patel SG, O'Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, Loomis AM, Shah JP. Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):122-137.
  15. Pickering CR, Zhang J, Neskey DM, Zhao M, Jasser SA, Wang J, Ward A, Tsai CJ, Ortega Alves MV, Zhou JH, Drummond J, El-Naggar AK, Gibbs R, Weinstein JN, Wheeler DA, Wang J, Frederick MJ, Myers JN. Squamous cell carcinoma of the oral tongue in young non-smokers is genomically similar to tumors in older smokers. Clin Cancer Res. 2014;20(14):3842-3848.
  16. Ng JH, Iyer NG, Tan MH, Edgren G. Changing epidemiology of oral squamous cell carcinoma of the tongue: A global study. Head Neck. 2017;39(2):297-304.