- ABSTRACT.
- INTRODUCTION
- NATURAL HISTORY OF HPV INFECTION
- PERSISTENT HPV INFECTION REQUIRES A TOLEROGENIC IMMUNE ENVIRONMENT
- CHRONIC GUT HELMINTH INFECTION PROMOTES A TOLEROGENIC SYSTEMIC IMMUNE ENVIRONMENT
- CHRONIC INTESTINAL HELMINTH-INDUCED SYSTEMIC IMMUNOMODULATION MAY ALLOW FOR VIRAL PERSISTENCE
- PUTTING IT ALL TOGETHER: INTESTINAL HELMINTH-INDUCED IMMUNE MECHANISMS COULD FACILITATE HRHPV PERSISTENCE AND EVENTUAL PROGRESSION TO CERVICAL CANCER
- APPLICATIONS OF IMPROVED UNDERSTANDING OF THE INTESTINAL HELMINTH–HPV RELATIONSHIP
- CONCLUSION
- References
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Gut Helminth Infection-Induced Immunotolerance and Consequences for Human Papillomavirus Persistence
Eva H. Clark
Eva H. Clark
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas;
Department of Medicine, Section of Health Services Research, Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, Texas;
National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;
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Department of Medicine, Section of Health Services Research, Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, Texas;
National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;
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Robert H. Gilman
Robert H. Gilman
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
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Elizabeth Y. Chiao
Elizabeth Y. Chiao
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas;
Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas;
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Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas;
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Patti E. Gravitt
Patti E. Gravitt
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland
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ABSTRACT.
Cervical cancer, a malignancy caused by persistent human papillomavirus (HPV) infection, develops in more than 500,000 women annually. More than 90% of deaths from cervical cancer occur in low- and middle-income countries. A common epidemiological feature of countries with high cervical cancer incidence is a high burden of intestinal helminth infection. The ability of intestinal helminths to trigger immunoregulation, resulting in a “tolerogenic” systemic immune environment, provides fertile soil for the persistence of oncogenic viruses such as HPV. Animal models have shown that intestinal helminth infection permits the persistence of some viruses, however, HPV-specific and human studies are lacking. Large, well-organized trials evaluating the consequences of intestinal helminth infection on the human immune system and HPV persistence may lead to improved strategies for HPV prevention in helminth-endemic regions of the world. Additionally, such studies would offer insight into the specific ways that intestinal helminth infection contributes to immunomodulation, which could identify new therapeutic targets for a range of diseases, from inflammatory disorders to cancer. In this review, we discuss the evidence for helminth-induced systemic and local immune dysregulation, discuss possible mechanisms by which chronic intestinal helminth infection may facilitate HPV persistence, and suggest novel helminth-related interventions that could offer a high leverage (if somewhat unconventional) approach to HPV and cervical cancer control in resource-constrained regions.
Author Notes
Financial support: This work was supported by VA Health Services Research & Development Center of Innovation grant CIN 13-413 (E. H. C. receives salary support in part from the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN13-413] Advanced Fellowships Program in Health Services Research).
Authors’ addresses: Eva H. Clark, Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, Department of Medicine, Section of Health Services Research, Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX, and National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, E-mail: eva.clark@bcm.edu. Robert H. Gilman, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: gilmanbob@gmail.com. Elizabeth Y. Chiao, Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, and Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, E-mail: eychiao@mdanderson.org. Patti E. Gravitt, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, E-mail: pgravitt@som.umaryland.edu.
- ABSTRACT.
- INTRODUCTION
- NATURAL HISTORY OF HPV INFECTION
- PERSISTENT HPV INFECTION REQUIRES A TOLEROGENIC IMMUNE ENVIRONMENT
- CHRONIC GUT HELMINTH INFECTION PROMOTES A TOLEROGENIC SYSTEMIC IMMUNE ENVIRONMENT
- CHRONIC INTESTINAL HELMINTH-INDUCED SYSTEMIC IMMUNOMODULATION MAY ALLOW FOR VIRAL PERSISTENCE
- PUTTING IT ALL TOGETHER: INTESTINAL HELMINTH-INDUCED IMMUNE MECHANISMS COULD FACILITATE HRHPV PERSISTENCE AND EVENTUAL PROGRESSION TO CERVICAL CANCER
- APPLICATIONS OF IMPROVED UNDERSTANDING OF THE INTESTINAL HELMINTH–HPV RELATIONSHIP
- CONCLUSION
- References
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