Grant Number:	5R01CA214588-05 Interpret this number
Primary Investigator:	Giuliano, Anna
Organization:	H. Lee Moffitt Cancer Ctr & Res Inst
Project Title:	Investigation of Oral HPV Infection Natural History and Biomarkers of Persistent Infection: the Him Study
Fiscal Year:	2021

ABSTRACT In 2013, 42,440 adults in the U.S. were diagnosed with oropharyngeal cancer (OPC), the majority at late stages, with an estimated five-year survival of 50% and a high rate of recurrence. Among those who survive, surgery and chemoradiotherapy leave patients with long-term pain, disfigurement, and disability that further add to the burden of the disease. Each year, OPCs are responsible for ~10,000 deaths, 130,000 years of potential life lost, and ~$3 billion in productivity loss. Earlier OPC diagnoses increase likelihood of single- modality treatment, lower the risk of mortality, decrease medical expenditures, and improve quality of life. HPV causes ~70% of OPCs in the US, with the proportion of OPCs due to HPV increasing each year. Incidence rates of HPV-related OPCs are also ~3-fold higher in males compared to females. While there is substantial literature regarding the natural history of genital HPV infection and progression to cervical cancer, little has been published on the natural history of oral HPV infection, thus limiting the development of OPC prevention interventions. Unlike cervical and anal cancers, no screening tests are available for OPC, nor have current HPV vaccines been evaluated for efficacy against these cancers. Therefore, in this grant application we propose to study oral HPV natural history through an established prospective cohort of average risk men, information urgently needed to inform the development of future prevention strategies, including clinically relevant screening tools. The HIM Study is the only male prospective study that has the cohort infrastructure and archived oral specimens to fill this critical research void. The overall goal of this research is to define the natural history of oral HPV infection to inform future development of OPC prevention and screening interventions. The central hypothesis is that viral, host, and behavioral factors are predictive of oral HPV infections that are most likely to persist ≥12 months (surrogate cancer endpoint), infections most likely to progress to cancer. We will estimate incidence and duration of oral HPV infections and associated factors. Novel viral (viral methylation, integration, variants), host (methylation), and behavioral (tobacco use, oral hygiene and health, sexual behavior,) factors will be evaluated in relation to oral HPV natural history. The proposed research is innovative, as it will be the first to prospectively address fundamental questions related to oral HPV natural history. Our study builds on an existing large data and biological specimen repository to efficiently address timely and significant questions identifying markers of infection that have utility for the design of future HPV-OPC screening/prevention interventions. Our transdisciplinary team of epidemiologists, biostatisticians, oncologists, and virologists has the experience and expertise to successfully implement the proposed study.




Control of Epstein-Barr Virus (EBV) in the Oral Cavity Is Associated With Persistence of Oral Human Papillomavirus (HPV)16/18 Among Men From the HPV Infection in Men Study.
Authors: Dickey B.L. , Giuliano A.R. , Sirak B. , Abrahamsen M. , Lazcano-Ponce E. , Villa L.L. , Coghill A.E. .
Source: The Journal of infectious diseases, 2023-01-11; 227(2), p. 256-260.
PMID: 35679351
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Methylation of HPV16 and EPB41L3 in oral gargles and the detection of early and late oropharyngeal cancer.
Authors: Dickey B.L. , Nedjai B. , Preece M.D. , Schell M.J. , Boulware D. , Whiting J. , Sirak B. , Abrahamsen M. , Isaacs-Soriano K.A. , Kennedy K. , et al. .
Source: Cancer medicine, 2022 Oct; 11(20), p. 3735-3742.
EPub date: 2022-05-26.
PMID: 35619332
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Factors Associated With Persistence and Clearance of High-Risk Oral Human Papillomavirus (HPV) Among Participants in the HPV Infection in Men (HIM) Study.
Authors: Bettampadi D. , Sirak B.A. , Abrahamsen M.E. , Reich R.R. , Villa L.L. , Ponce E.L. , Giuliano A.R. .
Source: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-11-02; 73(9), p. e3227-e3234.
PMID: 33173937
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Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males.
Authors: Dickey B.L. , Fan W. , Bettampadi D. , Reich R.R. , Sirak B. , Abrahamsen M. , Baggio M.L. , Galan L. , Silva R.C. , Salmerón J. , et al. .
Source: International journal of cancer, 2021-10-01; 149(7), p. 1483-1494.
EPub date: 2021-07-14.
PMID: 34224588
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Differences in Factors Associated With High- and Low-Risk Oral Human Papillomavirus Genotypes in Men.
Authors: Bettampadi D. , Dickey B. , Abrahamsen M. , Sirak B. , Baggio M.L. , Galan L. , Silva R.C. , Villa L. , Ponce E.L. , Giuliano A.R. .
Source: The Journal of infectious diseases, 2021-06-15; 223(12), p. 2099-2107.
PMID: 33151300
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Oral secretory leukocyte protease inhibitor (SLPI): Associations with oropharyngeal cancer and treatment outcome.
Authors: Dickey B.L. , Sirak B. , Martin-Gomez L. , Reich R.R. , Abrahamsen M. , Isaacs-Soriano K. , Chung C.H. , Giuliano A.R. .
Source: PloS one, 2021; 16(7), p. e0254161.
EPub date: 2021-07-02.
PMID: 34214131
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Oral HPV prevalence assessment by Linear Array vs. SPF₁₀ PCR-DEIA-LiPA₂₅ system in the HPV Infection in Men (HIM) study.
Authors: Bettampadi D. , Sirak B.A. , Fulp W.J. , Abrahamsen M. , Villa L.L. , Lazcano-Ponce E. , Salmeron J. , Isaacs-Soriano K.A. , Baggio M.L. , Trenado M.Q. , et al. .
Source: Papillomavirus research (Amsterdam, Netherlands), 2020 Jun; 9, p. 100199.
EPub date: 2020-05-25.
PMID: 32464335
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Oral human papillomavirus prevalence and type distribution by country (Brazil, Mexico and the United States) and age among HPV infection in men study participants.
Authors: Bettampadi D. , Villa L.L. , Ponce E.L. , Salmeron J. , Sirak B.A. , Abrahamsen M. , Rathwell J.A. , Reich R.R. , Giuliano A.R. .
Source: International journal of cancer, 2020-06-01; 146(11), p. 3026-3033.
EPub date: 2019-11-01.
PMID: 31583681
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Untangling the dynamics of persistence and colonization in microbial communities.
Authors: Ranjeva S.L. , Mihaljevic J.R. , Joseph M.B. , Giuliano A.R. , Dwyer G. .
Source: The ISME journal, 2019 Dec; 13(12), p. 2998-3010.
EPub date: 2019-08-23.
PMID: 31444482
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