Cervical cancer, caused by persistent infection with high risk human papillomavirus (HR-HPV) infection, remains the second leading cause of cancer in women in the world. Vaccines and screening are effective prevention measures, but are simply unaffordable in the countries with the greatest need. We are therefore interested in identifying modifiable factors associated with increased HPV prevalence and persistence as targets for low cost interventions in areas where HPV screening and vaccination are unlikely to be economically feasible. An ecological correlation is observed between regions with high cervical cancer incidence and high soil-transmitted helminth (STH) burden. We hypothesize that the well-known Th2-shift associated with intestinal helminth infection results in a decreased cell-mediated immune response to HPV infection, leading to higher prevalence and burden of multiple HPV infection in helminth-endemic regions. We therefore aim to determine the association between helminth infection and HPV prevalence and burden of multiple infections in women aged 25-45 years in low and high helminth endemic regions of Peru. We will also compare the distribution of cervical Th1/Th2/Treg cytokines in HPV positive vs. HPV negative women and in helminth negative vs. helminth positive women. As a subaim, women found to be infected with helminthes will be treated and HPV prevalence and cervical immune profiles compared before and after treatment. If our hypothesis is proven correct, periodic deforming, at a cost of US $0.21 - US $0.51 per treatment, would offer a highly affordable alternative to reducing the HR-HPV and cervical cancer burden in many resource-poor regions. Furthermore, a comprehensive evaluation of cervical cytokine profiles in reproductive age women from helminth-endemic and non-endemic regions of Peru will provide critical new data that may have a broader impact in areas including reproductive health and HIV prevention.

Public Health Relevance

Cervical cancer, caused by persistent infection with high risk human papillomavirus (HR-HPV) infection, remains the second leading cause of cancer in women in the world. Vaccines and screening are effective prevention measures, but are simply unaffordable in the countries with the greatest need. We hypothesize that the well-known Th2-shift associated with intestinal helminth infection results in a decreased cell-mediated immune response to HPV infection, leading to higher prevalence and burden of multiple HPV infection in helminth-endemic regions. If our hypothesis is proven correct, periodic deworming, at a cost of US $0.21 - US $0.51 per treatment, would offer a highly affordable alternative to reducing the HR-HPV and cervical cancer burden in many resource-poor regions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA156537-02
Application #
8212141
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
2011-01-11
Project End
2012-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2012
Total Cost
$156,461
Indirect Cost
$47,711
Name
Johns Hopkins University
Department
None
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Fakhry, Carole; Marks, Morgan A; Gilman, Robert H et al. (2013) Comparison of the immune microenvironment of the oral cavity and cervix in healthy women. Cytokine 64:597-604
Gravitt, Patti E (2011) The known unknowns of HPV natural history. J Clin Invest 121:4593-9