Program Official

Principal Investigator

Richard Bernard
Hayes
Awardee Organization

New York University School Of Medicine
United States

Fiscal Year
2024
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer

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 highrisk 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.

Publications

  • Peters BA, Wilson M, Moran U, Pavlick A, Izsak A, Wechter T, Weber JS, Osman I, Ahn J. Relating the gut metagenome and metatranscriptome to immunotherapy responses in melanoma patients. Genome medicine. 2019 Oct 9;11(1):61. PMID: 31597568
  • Ren W, Ma Y, Yang L, Gettie A, Salas J, Russell K, Blanchard J, Davidow A, Pei Z, Chang TL, Cheng-Mayer C. Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response. AIDS (London, England). 2015 Jun 19;29(10):F1-8. PMID: 26035329
  • Peters BA, Wu J, Hayes RB, Ahn J. The oral fungal mycobiome: characteristics and relation to periodontitis in a pilot study. BMC microbiology. 2017 Jul 12;17(1):157. PMID: 28701186
  • Hu J, Wang C, Blaser MJ, Li H. Joint modeling of zero-inflated longitudinal proportions and time-to-event data with application to a gut microbiome study. Biometrics. 2022 Dec;78(4):1686-1698. Epub 2021 Aug 1. PMID: 34213763
  • Ahn J, Hayes RB. Environmental Influences on the Human Microbiome and Implications for Noncommunicable Disease. Annual review of public health. 2021 Apr 1;42:277-292. PMID: 33798404
  • Guma S, Maglantay R, Lau R, Wieczorek R, Melamed J, Deng FM, Zhou M, Makarov D, Lee P, Pincus MR, Pei ZH. Papillary urothelial carcinoma with squamous differentiation in association with human papilloma virus: case report and literature review. American journal of clinical and experimental urology. 2016 Jan 28;4(1):12-6. eCollection 2016. PMID: 27069958
  • Prakash A, Peters BA, Cobbs E, Beggs D, Choi H, Li H, Hayes RB, Ahn J. Tobacco Smoking and the Fecal Microbiome in a Large, Multi-ethnic Cohort. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Jul;30(7):1328-1335. Epub 2021 May 21. PMID: 34020999
  • Wang C, Segal LN, Hu J, Zhou B, Hayes R, Ahn J, Li H. Microbial Risk Score for Capturing Microbial Characteristics, Integrating Multi-omics Data, and Predicting Disease Risk. bioRxiv : the preprint server for biology. 2022 Jun 8. PMID: 35702150
  • Dominianni C, Sinha R, Goedert JJ, Pei Z, Yang L, Hayes RB, Ahn J. Sex, body mass index, and dietary fiber intake influence the human gut microbiome. PloS one. 2015 Apr 15;10(4):e0124599. doi: 10.1371/journal.pone.0124599. eCollection 2015. PMID: 25874569
  • Ahn J, Yang L, Paster BJ, Ganly I, Morris L, Pei Z, Hayes RB. Oral microbiome profiles: 16S rRNA pyrosequencing and microarray assay comparison. PloS one. 2011;6(7):e22788. Epub 2011 Jul 29. PMID: 21829515
  • Neto AG, Whitaker A, Pei Z. Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma. Seminars in oncology. 2016 Feb;43(1):86-96. Epub 2015 Sep 7. PMID: 26970127
  • Brown SM, Chen H, Hao Y, Laungani BP, Ali TA, Dong C, Lijeron C, Kim B, Wultsch C, Pei Z, Krampis K. MGS-Fast: Metagenomic shotgun data fast annotation using microbial gene catalogs. GigaScience. 2019 Apr 1;8. (4). PMID: 30942867
  • Hickman RA, Bradshaw AD, Cassai N, Neto AG, Zhou D, Fu T, Lee P, Pei Z, Wieczorek R. A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: An immunohistochemical, molecular and ultrastructural study. Papillomavirus research (Amsterdam, Netherlands). 2016 Dec;2:164-166. Epub 2016 Sep 28. PMID: 28616595
  • Dominianni C, Wu J, Hayes RB, Ahn J. Comparison of methods for fecal microbiome biospecimen collection. BMC microbiology. 2014 Apr 23;14:103. PMID: 24758293
  • He L, Wang C, Hu J, Gao Z, Falcone E, Holland SM, Blaser MJ, Li H. ARZIMM: A Novel Analytic Platform for the Inference of Microbial Interactions and Community Stability from Longitudinal Microbiome Study. Frontiers in genetics. 2022 Feb 25;13:777877. doi: 10.3389/fgene.2022.777877. eCollection 2022. PMID: 35281829
  • Hickman RA, Yang L, Pei Z. "Nature versus Nurture" and the indigenous microbiome. Journal of public health and emergency. 2017 Mar;1. Epub 2017 Mar 16. PMID: 30246171
  • Peters BA, Dominianni C, Shapiro JA, Church TR, Wu J, Miller G, Yuen E, Freiman H, Lustbader I, Salik J, Friedlander C, Hayes RB, Ahn J. The gut microbiota in conventional and serrated precursors of colorectal cancer. Microbiome. 2016 Dec 30;4(1):69. PMID: 28038683
  • Um CY, Peters BA, Choi HS, Oberstein P, Beggs DB, Usyk M, Wu F, Hayes RB, Gapstur SM, McCullough ML, Ahn J. Grain, Gluten, and Dietary Fiber Intake Influence Gut Microbial Diversity: Data from the Food and Microbiome Longitudinal Investigation. Cancer research communications. 2023 Jan 11;3(1):43-53. doi: 10.1158/2767-9764.CRC-22-0154. eCollection 2023 Jan. PMID: 36968219
  • Usyk M, Hayes RB, Knight R, Gonzalez A, Li H, Osman I, Weber JS, Ahn J. Gut microbiome is associated with recurrence-free survival in patients with resected Stage IIIB-D or Stage IV melanoma treated with immune checkpoint inhibitors. bioRxiv : the preprint server for biology. 2024 Apr 20. PMID: 38659744
  • Ahn J, Chen CY, Hayes RB. Oral microbiome and oral and gastrointestinal cancer risk. Cancer causes & control : CCC. 2012 Mar;23(3):399-404. Epub 2012 Jan 22. PMID: 22271008
  • Ma Y, Madupu R, Karaoz U, Nossa CW, Yang L, Yooseph S, Yachimski PS, Brodie EL, Nelson KE, Pei Z. Human papillomavirus community in healthy persons, defined by metagenomics analysis of human microbiome project shotgun sequencing data sets. Journal of virology. 2014 May;88(9):4786-97. Epub 2014 Feb 12. PMID: 24522917
  • Cho M, Carter J, Harari S, Pei Z. The interrelationships of the gut microbiome and inflammation in colorectal carcinogenesis. Clinics in laboratory medicine. 2014 Dec;34(4):699-710. Epub 2014 Sep 15. PMID: 25439270
  • Pei A, Li H, Oberdorf WE, Alekseyenko AV, Parsons T, Yang L, Gerz EA, Lee P, Xiang C, Nossa CW, Pei Z. Diversity of 5S rRNA genes within individual prokaryotic genomes. FEMS microbiology letters. 2012 Oct;335(1):11-8. Epub 2012 Aug 2. PMID: 22765222
  • Baghdadi J, Chaudhary N, Pei Z, Yang L. Microbiome, innate immunity, and esophageal adenocarcinoma. Clinics in laboratory medicine. 2014 Dec;34(4):721-32. Epub 2014 Sep 26. PMID: 25439272
  • Shin H, Pei Z, Martinez KA 2nd, Rivera-Vinas JI, Mendez K, Cavallin H, Dominguez-Bello MG. The first microbial environment of infants born by C-section: the operating room microbes. Microbiome. 2015 Dec 1;3:59. PMID: 26620712
  • Fan X, Alekseyenko AV, Wu J, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, Abnet CC, Stolzenberg-Solomon R, Miller G, Ravel J, Hayes RB, Ahn J. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut. 2018 Jan;67(1):120-127. Epub 2016 Oct 14. PMID: 27742762
  • Usyk M, Pandey A, Hayes RB, Moran U, Pavlick A, Osman I, Weber JS, Ahn J. Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma. Genome medicine. 2021 Oct 13;13(1):160. PMID: 34641962
  • Ahn J, Segers S, Hayes RB. Periodontal disease, Porphyromonas gingivalis serum antibody levels and orodigestive cancer mortality. Carcinogenesis. 2012 May;33(5):1055-8. Epub 2012 Feb 26. PMID: 22367402
  • Yang L, Francois F, Pei Z. Molecular pathways: pathogenesis and clinical implications of microbiome alteration in esophagitis and Barrett esophagus. Clinical cancer research : an official journal of the American Association for Cancer Research. 2012 Apr 15;18(8):2138-44. Epub 2012 Feb 16. PMID: 22344232
  • Pincus MR, Pei Z. Beyond infectious disease: welcome to the era of population microbiology. Clinics in laboratory medicine. 2014 Dec;34(4):xi-xiii. Epub 2014 Oct 31. PMID: 25439278
  • Hu J, Nomura Y, Bashir A, Fernandez-Hernandez H, Itzkowitz S, Pei Z, Stone J, Loudon H, Peter I. Diversified microbiota of meconium is affected by maternal diabetes status. PloS one. 2013 Nov 6;8(11):e78257. doi: 10.1371/journal.pone.0078257. eCollection 2013. PMID: 24223144
  • Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, Goedert JJ, Hayes RB, Yang L. Human gut microbiome and risk for colorectal cancer. Journal of the National Cancer Institute. 2013 Dec 18;105(24):1907-11. Epub 2013 Dec 6. PMID: 24316595
  • Monson KR, Peters BA, Usyk M, Um CY, Oberstein PE, McCullough ML, Purdue MP, Freedman ND, Hayes RB, Ahn J. Elevated dietary carbohydrate and glycemic intake associate with an altered oral microbial ecosystem in two large U.S. cohorts. Cancer research communications. 2022 Dec;2(12):1558-1568. Epub 2022 Dec 5. PMID: 36567732
  • Fan X, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, Freedman ND, Alekseyenko AV, Wu J, Yang L, Pei Z, Hayes RB, Ahn J. Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults. Microbiome. 2018 Apr 24;6(1):59. PMID: 29685174
  • Neto AG, Bradshaw AD, Pei Z. Microbiome, a new dimension in cancer research. Annals of translational medicine. 2015 Sep;3(16):229. PMID: 26539446
  • Fan X, Peters BA, Min D, Ahn J, Hayes RB. Comparison of the oral microbiome in mouthwash and whole saliva samples. PloS one. 2018 Apr 11;13(4):e0194729. doi: 10.1371/journal.pone.0194729. eCollection 2018. PMID: 29641531
  • Peters BA, Yi SS, Beasley JM, Cobbs EN, Choi HS, Beggs DB, Hayes RB, Ahn J. US nativity and dietary acculturation impact the gut microbiome in a diverse US population. The ISME journal. 2020 Jul;14(7):1639-1650. Epub 2020 Mar 24. PMID: 32210364
  • Xu W, Yang L, Lee P, Huang WC, Nossa C, Ma Y, Deng FM, Zhou M, Melamed J, Pei Z. Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma. American journal of clinical and experimental urology. 2014 Apr 15;2(1):57-61. PMID: 25126590
  • Lin D, Peters BA, Friedlander C, Freiman HJ, Goedert JJ, Sinha R, Miller G, Bernstein MA, Hayes RB, Ahn J. Association of dietary fibre intake and gut microbiota in adults. The British journal of nutrition. 2018 Nov;120(9):1014-1022. PMID: 30355393
  • Bravi F, Lee YA, Hashibe M, Boffetta P, Conway DI, Ferraroni M, La Vecchia C, Edefonti V, INHANCE Consortium investigators, Agudo A, Ahrens W, Benhamou S, Boccia S, Brennan P, Brenner H, Cadoni G, Canova C, Chen C, Chuang SC, Curado MP, Dal Maso L, Daudt AW, D'Souza G, Fabianova E, Fernandez L, Franceschi S, Garavello W, Gillison M, Gross ND, Hayes RB, Healy C, Herrero R, Holcatova I, Kelsey K, Kjaerheim K, Koifman R, Lagiou P, Lazarus P, Levi F, Li G, Lissowska J, Luce D, Macfarlane GJ, Mates D, Matsuo K, McClean M, Menezes A, Menvielle G, Morgenstern H, Moyses RA, Moysich K, Muscat J, Negri E, Olshan AF, Pandics T, Polesel J, Purdue MP, Radoï L, Ramroth H, Richiardi L, Schantz S, Schwartz SM, Serraino D, Shangina O, Smith E, Sturgis EM, Świątkowska B, Thomson P, Toporcov TN, Vaughan TL, Vilensky M, Winn DM, Wunsch-Filho V, Yu GP, Zevallos JP, Zhang ZF, Zheng T, Znaor A. Lessons learned from the INHANCE consortium: An overview of recent results on head and neck cancer. Oral diseases. 2021 Jan;27(1):73-93. Epub 2020 Jul 16. PMID: 32569410
  • Hayes RB, Ahn J, Fan X, Peters BA, Ma Y, Yang L, Agalliu I, Burk RD, Ganly I, Purdue MP, Freedman ND, Gapstur SM, Pei Z. Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer. JAMA oncology. 2018 Mar 1;4(3):358-365. PMID: 29327043
  • Peters BA, McCullough ML, Purdue MP, Freedman ND, Um CY, Gapstur SM, Hayes RB, Ahn J. Association of Coffee and Tea Intake with the Oral Microbiome: Results from a Large Cross-Sectional Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2018 Jul;27(7):814-821. Epub 2018 Apr 27. PMID: 29703763
  • Shin H, Pei Z, Martinez KA 2nd, Rivera-Vinas JI, Mendez K, Cavallin H, Dominguez-Bello MG. Erratum to: The first microbial environment of infants born by C-section: the operating room microbes. Microbiome. 2016 Jan 21;4:4. PMID: 26796629
  • Wu J, Peters BA, Dominianni C, Zhang Y, Pei Z, Yang L, Ma Y, Purdue MP, Jacobs EJ, Gapstur SM, Li H, Alekseyenko AV, Hayes RB, Ahn J. Cigarette smoking and the oral microbiome in a large study of American adults. The ISME journal. 2016 Oct;10(10):2435-46. Epub 2016 Mar 25. PMID: 27015003
  • Kwak S, Usyk M, Beggs D, Choi H, Ahdoot D, Wu F, Maceda L, Li H, Im EO, Han HR, Lee E, Wu AH, Hayes RB, Ahn J. Sociobiome - Individual and neighborhood socioeconomic status influence the gut microbiome in a multi-ethnic population in the US. NPJ biofilms and microbiomes. 2024 Mar 11;10(1):19. PMID: 38467678
  • Yang L, Chaudhary N, Baghdadi J, Pei Z. Microbiome in reflux disorders and esophageal adenocarcinoma. Cancer journal (Sudbury, Mass.). 2014 May-Jun;20(3):207-10. PMID: 24855009
  • Peters BA, Shapiro JA, Church TR, Miller G, Trinh-Shevrin C, Yuen E, Friedlander C, Hayes RB, Ahn J. A taxonomic signature of obesity in a large study of American adults. Scientific reports. 2018 Jun 27;8(1):9749. PMID: 29950689
  • Mu EW, Khurram NA, Pei Z, Feng H, Cassai N, Meehan SA, Latkowski JA. 55-year-old man with ulcers in inguinal fold and intergluteal cleft found to have systemic Langerhans cell histiocytosis. JAAD case reports. 2018 Sep 18;4(8):837-840. doi: 10.1016/j.jdcr.2018.05.016. eCollection 2018 Sep. PMID: 30238052
  • Dominianni C, Huang WY, Berndt S, Hayes RB, Ahn J. Prospective study of the relationship between coffee and tea with colorectal cancer risk: the PLCO Cancer Screening Trial. British journal of cancer. 2013 Sep 3;109(5):1352-9. Epub 2013 Aug 1. PMID: 23907431
  • Yang L, Poles MA, Fisch GS, Ma Y, Nossa C, Phelan JA, Pei Z. HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria. AIDS (London, England). 2016 Jan 2;30(1):19-29. PMID: 26731752
  • Peters BA, Pass HI, Burk RD, Xue X, Goparaju C, Sollecito CC, Grassi E, Segal LN, Tsay JJ, Hayes RB, Ahn J. The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer. Genome medicine. 2022 Oct 27;14(1):121. PMID: 36303210
  • Sulaiman I, Chung M, Angel L, Tsay JJ, Wu BG, Yeung ST, Krolikowski K, Li Y, Duerr R, Schluger R, Thannickal SA, Koide A, Rafeq S, Barnett C, Postelnicu R, Wang C, Banakis S, Pérez-Pérez L, Shen G, Jour G, Meyn P, Carpenito J, Liu X, Ji K, Collazo D, Labarbiera A, Amoroso N, Brosnahan S, Mukherjee V, Kaufman D, Bakker J, Lubinsky A, Pradhan D, Sterman DH, Weiden M, Heguy A, Evans L, Uyeki TM, Clemente JC, de Wit E, Schmidt AM, Shopsin B, Desvignes L, Wang C, Li H, Zhang B, Forst CV, Koide S, Stapleford KA, Khanna KM, Ghedin E, Segal LN. Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome. Nature microbiology. 2021 Oct;6(10):1245-1258. Epub 2021 Aug 31. PMID: 34465900
  • Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, Hayes RB, Goedert JJ. Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations. PloS one. 2016 Mar 25;11(3):e0152126. doi: 10.1371/journal.pone.0152126. eCollection 2016. PMID: 27015276
  • Ahn J, Kwak S, Usyk M, Beggs D, Choi H, Ahdoot D, Wu F, Maceda L, Li H, Im EO, Han HR, Lee E, Wu A, Hayes R. Sociobiome - Individual and neighborhood socioeconomic status influence the gut microbiome in a multi-ethnic population in the US. Research square. 2023 Apr 19. PMID: 37131763
  • Di Credico G, Polesel J, Dal Maso L, Pauli F, Torelli N, Luce D, Radoï L, Matsuo K, Serraino D, Brennan P, Holcatova I, Ahrens W, Lagiou P, Canova C, Richiardi L, Healy CM, Kjaerheim K, Conway DI, Macfarlane GJ, Thomson P, Agudo A, Znaor A, Franceschi S, Herrero R, Toporcov TN, Moyses RA, Muscat J, Negri E, Vilensky M, Fernandez L, Curado MP, Menezes A, Daudt AW, Koifman R, Wunsch-Filho V, Olshan AF, Zevallos JP, Sturgis EM, Li G, Levi F, Zhang ZF, Morgenstern H, Smith E, Lazarus P, La Vecchia C, Garavello W, Chen C, Schwartz SM, Zheng T, Vaughan TL, Kelsey K, McClean M, Benhamou S, Hayes RB, Purdue MP, Gillison M, Schantz S, Yu GP, Chuang SC, Boffetta P, Hashibe M, Yuan-Chin AL, Edefonti V. Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration. British journal of cancer. 2020 Oct;123(9):1456-1463. Epub 2020 Aug 24. PMID: 32830199
  • Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R. Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. Epub 2014 Jul 18. PMID: 25037050
  • Peters BA, Wu J, Pei Z, Yang L, Purdue MP, Freedman ND, Jacobs EJ, Gapstur SM, Hayes RB, Ahn J. Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers. Cancer research. 2017 Dec 1;77(23):6777-6787. PMID: 29196415