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 #
5R01CA098803-10
Application #
8586232
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
2014-02-05
Budget End
2014-11-30
Support Year
10
Fiscal Year
2014
Total Cost
$1,762,716
Indirect Cost
$517,856
Name
H. Lee Moffitt Cancer Center & Research Institute
Department
Type
DUNS #
139301956
City
Tampa
State
FL
Country
United States
Zip Code
33612
Mainali, Bigyan; Schabath, Matthew B; Sudenga, Staci L et al. (2018) Variants in immune-related genes and genital HPV 16 persistence in men. Papillomavirus Res 7:11-14
Beachler, Daniel C; Pinto, Ligia A; Kemp, Troy J et al. (2018) An Examination of HPV16 Natural Immunity in Men Who Have Sex with Men (MSM) in the HPV in Men (HIM) Study. Cancer Epidemiol Biomarkers Prev 27:496-502
Nunes, Emily M; López, Rossana V M; Sudenga, Staci L et al. (2017) Concordance of Beta-papillomavirus across anogenital and oral anatomic sites of men: The HIM Study. Virology 510:55-59
Sudenga, Staci L; Nyitray, Alan G; Torres, B Nelson et al. (2017) Comparison of anal HPV natural history among men by country of residence: Brazil, Mexico, and the United States. J Infect 75:35-47
Rahman, Shams; Giuliano, Anna R; Rollison, Dana E et al. (2017) Cutaneous HPV and alpha-mucosal 9-valent HPV sero-status associations. Papillomavirus Res 4:54-57
Sudenga, Staci L; Torres, B Nelson; Fulp, William J et al. (2017) Country-specific HPV-related genital disease among men residing in Brazil, Mexico and The United States: The HIM study. Int J Cancer 140:337-345
Sudenga, Staci L; Torres, B Nelson; Silva, Roberto et al. (2017) Comparison of the Natural History of Genital HPV Infection among Men by Country: Brazil, Mexico, and the United States. Cancer Epidemiol Biomarkers Prev 26:1043-1052
da Silva, Roberto Jose Carvalho; Sudenga, Staci Lynn; Sichero, Laura et al. (2017) HPV-related external genital lesions among men residing in Brazil. Braz J Infect Dis 21:376-385
Hampras, Shalaka S; Rollison, Dana E; Giuliano, Anna R et al. (2017) Prevalence and Concordance of Cutaneous Beta Human Papillomavirus Infection at Mucosal and Cutaneous Sites. J Infect Dis 216:92-96
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

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