We hypothesize that oral microbiota influence squamous cell head and neck cancer (SCHNC) development, potentially related to carcinogen metabolism. The human oral cavity hosts a diverse microbiota, including bacteria and fungi. In the previous R01 cycle, we made the novel discovery that oral bacteria are associated with SCHNC. In this competitive R01 renewal application, we focus on oral fungi (the mycobiome). Oral fungi activate carcinogens and promote inflammation and oral carcinogenesis. Fungi are commonly isolated from oral cancers and pre-cancers. Furthermore, patients with fungal Candida clinical infection have increased risk for SCHNC. Despite this evidence, there is limited knowledge about the direct relationship of oral fungi with development of SCHNC in the general population. Our ultimate goal is to identify microbial determinants of SCHNC which may lead to novel microbially-based approaches for SCHNC prevention.
Our specific aims are 1) to test if oral fungi influence the development of SCHNC, 2) to test if oral fungi and bacteria jointly influence the development of this disease and 3) to determine whether oral fungi and bacteria contribute to oral microbial functional pathways for carcinogen metabolism. The study includes 339 incident SCHNC cases and 339 nested controls in the NCI-PLCO, ACS-Cancer Prevention Study-II and the Southern Community Cohort Study. More than 468,000 SCHNC cases and 323,000 related deaths occur annually worldwide. Knowledge gained from this study will increase our understanding of the etiology of SCHNC. The study will serve to identify high- risk subjects, based on oral microbial status. Pre-diagnostic microbiota found in this prospective study may lead to new microbial approaches for personalized prevention of this disease.

Public Health Relevance

Squamous cell head and neck cancer (SCHNC) is a dreadful disease with significant physical disfigurement and poor survival rates. In this large prospective study, we will test the hypothesis that oral (fungal) mycobiome influences SCHNC development, potentially related to alcohol and tobacco carcinogen metabolism. Knowledge gained from this study will increase our understanding of the etiology of SCHNC, help to identify high-risk subjects, and may lead to new approaches for prevention of this disease.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Cancer, Heart, and Sleep Epidemiology A Study Section (CHSA)
Program Officer
Zhu, Claire
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York University
Internal Medicine/Medicine
Schools of Medicine
New York
United States
Zip Code
Fan, Xiaozhou; Peters, Brandilyn A; Jacobs, Eric J et al. (2018) Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults. Microbiome 6:59
Hayes, Richard B; Ahn, Jiyoung; Fan, Xiaozhou et al. (2018) Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer. JAMA Oncol 4:358-365
Fan, Xiaozhou; Peters, Brandilyn A; Min, Deborah et al. (2018) Comparison of the oral microbiome in mouthwash and whole saliva samples. PLoS One 13:e0194729
Mu, Euphemia W; Khurram, Nigar Anjuman; Pei, Zhiheng et al. (2018) 55-year-old man with ulcers in inguinal fold and intergluteal cleft found to have systemic Langerhans cell histiocytosis. JAAD Case Rep 4:837-840
Fan, Xiaozhou; Alekseyenko, Alexander V; Wu, Jing et al. (2018) Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut 67:120-127
Peters, Brandilyn A; Wu, Jing; Pei, Zhiheng et al. (2017) Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers. Cancer Res 77:6777-6787
Hickman, Richard A; Yang, Liying; Pei, Zhiheng (2017) ""Nature versus Nurture"" and the indigenous microbiome. J Public Health Emerg 1:
Peters, Brandilyn A; Wu, Jing; Hayes, Richard B et al. (2017) The oral fungal mycobiome: characteristics and relation to periodontitis in a pilot study. BMC Microbiol 17:157
Hickman, Richard A; Bradshaw, Azore-Dee; Cassai, Nicholas et al. (2016) A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: An immunohistochemical, molecular and ultrastructural study. Papillomavirus Res 2:164-166
Peters, Brandilyn A; Dominianni, Christine; Shapiro, Jean A et al. (2016) The gut microbiota in conventional and serrated precursors of colorectal cancer. Microbiome 4:69

Showing the most recent 10 out of 36 publications