Little is known about the progression of genital HPV infections to disease in men. Just as these data were critical to the successful development and implementation of HPV vaccines for women, they are also critical to the development of vaccines targeting men. HPV-related external genital lesions (EGLs) consist of two categories: condyloma (genital warts) and penile intraepithelial neoplasia (PIN). The overall goal of this Natural History of HPV Infection in Men (HIM) Study competitive renewal application is to define the natural history of HPV-related EGL development in men. The central hypothesis is that EGL incidence in men is significantly associated with age and HPV type-specific antibody status, and influenced by HPV type distribution and infection duration.
The specific aims are: 1. Estimate the age-specific incidence of EGL (condyloma, PIN) by pathologic evaluation;2. Determine the proportion of HPV infections that progress to EGL and time to EGL;3. Evaluate if type-specific HPV capsid antibody response reduces the risk of subsequent persistent HPV infection and incident EGL, and;4. Assess whether age and circumcision status are independently associated with EGL incidence in men. To achieve the aims, clinical, viral, immune, and pathological parameters will be integrated. We will complete 4 years of active follow-up of 3450 HIM Study cohort participants ages 18-70 yrs., examined every 6 months, to ascertain external genital HPV DNA, pathologically confirmed EGLs, sexually transmitted infections (STI), HPV antibody status, and sexual and other behavioral risk factors. We will assess HPV 16 integration, quantitate HPV viral load, and utilize viral sequencing to improve definitions of persistence and assess its role in lesion development. We will evaluate antibody status prospectively to assess associations with HPV disease progression and utilize pathologic analysis to provide the first prospective estimate of the incidence of histologically defined EGLs in men over a large age range. The proposed research is innovative, as it will be the first to prospectively assess HPV infection progression to EGLs in men. As PIN and genital warts may be important reservoirs of infection for transmission, these lesions have significance for the disease status of the male as well as his sexual partner(s). Our study is timely and significant in that it will yield data on types of HPV infection that lead to EGLs in men, information needed to assess population effectiveness of the existing quadrivalent HPV vaccine in men and development of new multi-valent vaccines. The study will make a significant scientific contribution to knowledge of HPV humoral immunity and molecular virology of HPV in relation to genital disease in men utilizing multiple measures of sexual activity, molecular markers of HPV infection, and HPV antibody response. Our research team has the experience and expertise to successfully implement the proposed study. Finally, the HIM Study has established a data and biological specimen repository and the requisite infrastructure with which to test future and ancillary scientific hypotheses related to HPV infection in men.

Public Health Relevance

Little is known about the progression of genital HPV infections to disease in men. Just as these data were critical to the successful development and implementation of HPV vaccines for women, they are also critical to the development of vaccines targeting men. The overall goal of this Natural History of HPV Infection in Men (HIM) Study competitive renewal application is to define the natural history of HPV-related genital disease in men. The central hypothesis is that genital disease incidence in men is significantly associated with age and HPV antibody status, and influenced by HPV type and infection duration. To our knowledge this proposed research is the first to prospectively assess HPV infection progression to genital disease in men. As these lesions may be important reservoirs of infection for transmission, they have significance for the disease status of the male as well as his sexual partner(s). In addition to the significant scientific contribution this study will make, the HIM Study has established a data and biological specimen repository with which to test future and ancillary scientific hypotheses related to HPV infection and disease in men.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA098803-09
Application #
8387032
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Starks, Vaurice
Project Start
2003-01-01
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
9
Fiscal Year
2013
Total Cost
$1,783,975
Indirect Cost
$491,603
Name
H. Lee Moffitt Cancer Center & Research Institute
Department
Type
DUNS #
139301956
City
Tampa
State
FL
Country
United States
Zip Code
33612
Sudenga, Staci L; Ingles, Donna J; Pierce Campbell, Christine M et al. (2016) Genital Human Papillomavirus Infection Progression to External Genital Lesions: The HIM Study. Eur Urol 69:166-73
Nunes, Emily Montosa; Sudenga, Staci L; Gheit, Tarik et al. (2016) Diversity of beta-papillomavirus at anogenital and oral anatomic sites of men: The HIM Study. Virology 495:33-41
Yin, Li; Yao, Jin; Chang, Kaifen et al. (2016) HPV Population Profiling in Healthy Men by Next-Generation Deep Sequencing Coupled with HPV-QUEST. Viruses 8:
Pierce Campbell, Christine M; Viscidi, Raphael P; Torres, B Nelson et al. (2016) Human Papillomavirus (HPV) L1 Serum Antibodies and the Risk of Subsequent Oral HPV Acquisition in Men: The HIM Study. J Infect Dis 214:45-8
Pamnani, Shitaldas J; Nyitray, Alan G; Abrahamsen, Martha et al. (2016) Sequential Acquisition of Anal Human Papillomavirus (HPV) Infection Following Genital Infection Among Men Who Have Sex With Women: The HPV Infection in Men (HIM) Study. J Infect Dis 214:1180-7
Rahman, S; Pierce Campbell, C M; Torres, B N et al. (2016) Distribution and factors associated with salivary secretory leukocyte protease inhibitor concentrations. Oral Dis 22:781-790
Pamnani, Shitaldas J; Sudenga, Staci L; Viscidi, Raphael et al. (2016) Impact of Serum Antibodies to HPV Serotypes 6, 11, 16, and 18 to Risks of Subsequent Genital HPV Infections in Men: The HIM Study. Cancer Res 76:6066-6075
Nyitray, Alan G; Chang, Mihyun; Villa, Luisa L et al. (2015) The natural history of genital human papillomavirus among HIV-negative men having sex with men and men having sex with women. J Infect Dis 212:202-12
Schabath, Matthew B; Thompson, Zachary J; Egan, Kathleen M et al. (2015) Alcohol consumption and prevalence of human papillomavirus (HPV) infection among US men in the HPV in Men (HIM) study. Sex Transm Infect 91:61-7
Sichero, L; Nyitray, A G; Nunes, E M et al. (2015) Diversity of human papillomavirus in the anal canal of men: the HIM Study. Clin Microbiol Infect 21:502-9

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