Clinician's guide to human papillomavirus immunology: knowns and unknowns

Mark H. Einstein, John T. Schiller, Raphael P. Viscidi, Howard D. Strickler, Pierre Coursaget, Tina Tan, Neal Halsey, David Jenkins

Research output: Contribution to journalReview article

136 Citations (Scopus)

Abstract

Oncogenic human papillomavirus (HPV) is a common genital infection that has the potential to develop into cervical cancer in some women. This Review summarises current knowledge on the mechanisms of host immunity that help prevent and control HPV infection and the viral factors that exist to avoid immune surveillance. Although most women clear the infection within a few months, the virus induces a shift towards immune tolerance that can facilitate persistence and permit tumorigenesis. Mechanisms used by HPV to avoid immune surveillance and control include infecting only the basal layer of the cervical epithelium, limiting expression of viral proteins until later stages of epithelial differentiation, undergoing non-lytic replication, and downregulating the expression of important receptors on cells of the innate immune system. Furthermore, HPV suppresses the expression of several proinflammatory proteins that are crucial in clearing infection and activating the cytotoxic T lymphocytes involved in killing virus-infected cells. Interestingly, neutralising antibodies, although of uncertain effectiveness in preventing infection or reinfection after natural exposure (prior infection), are highly protective after immunisation with HPV virus-like-particle-based vaccines. Understanding what is known and unknown about the interaction between the immune system and HPV is important in the assessment of the potential contribution of prophylactic vaccination in reducing the incidence of cervical cancer. However, despite our growing understanding, many aspects of the interactions between HPV and the host immune system remain unknown, and this Review draws attention to several of these unresolved issues and their implications.

Original languageEnglish (US)
Pages (from-to)347-356
Number of pages10
JournalThe Lancet infectious diseases
Volume9
Issue number6
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

Fingerprint

Allergy and Immunology
Immune System
Infection
Papillomaviridae
Uterine Cervical Neoplasms
Virus-Like Particle Vaccines
Viruses
Papillomavirus Vaccines
Immune Tolerance
Papillomavirus Infections
Cytotoxic T-Lymphocytes
Viral Proteins
Neutralizing Antibodies
Immunity
Immunization
Carcinogenesis
Vaccination
Down-Regulation
Epithelium
Incidence

All Science Journal Classification (ASJC) codes

  • Infectious Diseases

Cite this

Einstein, M. H., Schiller, J. T., Viscidi, R. P., Strickler, H. D., Coursaget, P., Tan, T., ... Jenkins, D. (2009). Clinician's guide to human papillomavirus immunology: knowns and unknowns. The Lancet infectious diseases, 9(6), 347-356. https://doi.org/10.1016/S1473-3099(09)70108-2
Einstein, Mark H. ; Schiller, John T. ; Viscidi, Raphael P. ; Strickler, Howard D. ; Coursaget, Pierre ; Tan, Tina ; Halsey, Neal ; Jenkins, David. / Clinician's guide to human papillomavirus immunology : knowns and unknowns. In: The Lancet infectious diseases. 2009 ; Vol. 9, No. 6. pp. 347-356.
@article{c9bd0c597a0549148ff52ced9fcaabed,
title = "Clinician's guide to human papillomavirus immunology: knowns and unknowns",
abstract = "Oncogenic human papillomavirus (HPV) is a common genital infection that has the potential to develop into cervical cancer in some women. This Review summarises current knowledge on the mechanisms of host immunity that help prevent and control HPV infection and the viral factors that exist to avoid immune surveillance. Although most women clear the infection within a few months, the virus induces a shift towards immune tolerance that can facilitate persistence and permit tumorigenesis. Mechanisms used by HPV to avoid immune surveillance and control include infecting only the basal layer of the cervical epithelium, limiting expression of viral proteins until later stages of epithelial differentiation, undergoing non-lytic replication, and downregulating the expression of important receptors on cells of the innate immune system. Furthermore, HPV suppresses the expression of several proinflammatory proteins that are crucial in clearing infection and activating the cytotoxic T lymphocytes involved in killing virus-infected cells. Interestingly, neutralising antibodies, although of uncertain effectiveness in preventing infection or reinfection after natural exposure (prior infection), are highly protective after immunisation with HPV virus-like-particle-based vaccines. Understanding what is known and unknown about the interaction between the immune system and HPV is important in the assessment of the potential contribution of prophylactic vaccination in reducing the incidence of cervical cancer. However, despite our growing understanding, many aspects of the interactions between HPV and the host immune system remain unknown, and this Review draws attention to several of these unresolved issues and their implications.",
author = "Einstein, {Mark H.} and Schiller, {John T.} and Viscidi, {Raphael P.} and Strickler, {Howard D.} and Pierre Coursaget and Tina Tan and Neal Halsey and David Jenkins",
year = "2009",
month = "6",
day = "1",
doi = "https://doi.org/10.1016/S1473-3099(09)70108-2",
language = "English (US)",
volume = "9",
pages = "347--356",
journal = "The Lancet Infectious Diseases",
issn = "1473-3099",
publisher = "Lancet Publishing Group",
number = "6",

}

Einstein, MH, Schiller, JT, Viscidi, RP, Strickler, HD, Coursaget, P, Tan, T, Halsey, N & Jenkins, D 2009, 'Clinician's guide to human papillomavirus immunology: knowns and unknowns', The Lancet infectious diseases, vol. 9, no. 6, pp. 347-356. https://doi.org/10.1016/S1473-3099(09)70108-2

Clinician's guide to human papillomavirus immunology : knowns and unknowns. / Einstein, Mark H.; Schiller, John T.; Viscidi, Raphael P.; Strickler, Howard D.; Coursaget, Pierre; Tan, Tina; Halsey, Neal; Jenkins, David.

In: The Lancet infectious diseases, Vol. 9, No. 6, 01.06.2009, p. 347-356.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Clinician's guide to human papillomavirus immunology

T2 - knowns and unknowns

AU - Einstein, Mark H.

AU - Schiller, John T.

AU - Viscidi, Raphael P.

AU - Strickler, Howard D.

AU - Coursaget, Pierre

AU - Tan, Tina

AU - Halsey, Neal

AU - Jenkins, David

PY - 2009/6/1

Y1 - 2009/6/1

N2 - Oncogenic human papillomavirus (HPV) is a common genital infection that has the potential to develop into cervical cancer in some women. This Review summarises current knowledge on the mechanisms of host immunity that help prevent and control HPV infection and the viral factors that exist to avoid immune surveillance. Although most women clear the infection within a few months, the virus induces a shift towards immune tolerance that can facilitate persistence and permit tumorigenesis. Mechanisms used by HPV to avoid immune surveillance and control include infecting only the basal layer of the cervical epithelium, limiting expression of viral proteins until later stages of epithelial differentiation, undergoing non-lytic replication, and downregulating the expression of important receptors on cells of the innate immune system. Furthermore, HPV suppresses the expression of several proinflammatory proteins that are crucial in clearing infection and activating the cytotoxic T lymphocytes involved in killing virus-infected cells. Interestingly, neutralising antibodies, although of uncertain effectiveness in preventing infection or reinfection after natural exposure (prior infection), are highly protective after immunisation with HPV virus-like-particle-based vaccines. Understanding what is known and unknown about the interaction between the immune system and HPV is important in the assessment of the potential contribution of prophylactic vaccination in reducing the incidence of cervical cancer. However, despite our growing understanding, many aspects of the interactions between HPV and the host immune system remain unknown, and this Review draws attention to several of these unresolved issues and their implications.

AB - Oncogenic human papillomavirus (HPV) is a common genital infection that has the potential to develop into cervical cancer in some women. This Review summarises current knowledge on the mechanisms of host immunity that help prevent and control HPV infection and the viral factors that exist to avoid immune surveillance. Although most women clear the infection within a few months, the virus induces a shift towards immune tolerance that can facilitate persistence and permit tumorigenesis. Mechanisms used by HPV to avoid immune surveillance and control include infecting only the basal layer of the cervical epithelium, limiting expression of viral proteins until later stages of epithelial differentiation, undergoing non-lytic replication, and downregulating the expression of important receptors on cells of the innate immune system. Furthermore, HPV suppresses the expression of several proinflammatory proteins that are crucial in clearing infection and activating the cytotoxic T lymphocytes involved in killing virus-infected cells. Interestingly, neutralising antibodies, although of uncertain effectiveness in preventing infection or reinfection after natural exposure (prior infection), are highly protective after immunisation with HPV virus-like-particle-based vaccines. Understanding what is known and unknown about the interaction between the immune system and HPV is important in the assessment of the potential contribution of prophylactic vaccination in reducing the incidence of cervical cancer. However, despite our growing understanding, many aspects of the interactions between HPV and the host immune system remain unknown, and this Review draws attention to several of these unresolved issues and their implications.

UR - http://www.scopus.com/inward/record.url?scp=65849518739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65849518739&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/S1473-3099(09)70108-2

DO - https://doi.org/10.1016/S1473-3099(09)70108-2

M3 - Review article

C2 - 19467474

VL - 9

SP - 347

EP - 356

JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

SN - 1473-3099

IS - 6

ER -