Persistence of Human Papillomavirus Infection: Keys to Malignant Progression

Overview

Journal Trends Microbiol

Date 2010 Nov 6

PMID 21050765

Citations 161

Authors

Jason Bodily

Laimonis A Laimins

Affiliations

Soon will be listed here.

Abstract

Human papillomaviruses (HPVs) are the etiologic agents of cervical and other epithelial cancers. Persistence of infections by high-risk HPV types is the single greatest risk factor for malignant progression. Although prophylactic vaccines have been developed that target high-risk HPV types, there is a continuing need to understand better the virus-host interactions that underlie persistent benign infection and progression to cancer. In this review we summarize the molecular events that facilitate the differentiation-dependent HPV life cycle, how the life cycle is organized to facilitate virus persistence, and how the activities of HPV regulatory proteins result in malignancy.

Citing Articles

Regulation of Granzymes A and B by High-Risk HPV: Impact on Immune Evasion and Carcinogenesis.

Maleka M, Mbita Z, Morafo V Viruses. 2025; 17(2).

PMID: 40006976 PMC: 11861749. DOI: 10.3390/v17020221.

Evaluating HPV Viral Load and Multiple Infections for Enhanced Cervical Cancer Risk-Based Assessment.

Varesano S, Ciccarese G, Paudice M, Mazzocco K, Gaggero G, Ferrero S Life (Basel). 2025; 15(2).

PMID: 40003564 PMC: 11856100. DOI: 10.3390/life15020153.

Impact of HIV on HPV-related cancers in men who have sex with men: a review.

Zhang Z, Xing Y, Gong T, Li W, Zhang S, Wei L Front Cell Infect Microbiol. 2025; 14:1428491.

PMID: 39902182 PMC: 11788171. DOI: 10.3389/fcimb.2024.1428491.

RFC3 Knockdown Decreases Cervical Cancer Cell Proliferation, Migration and Invasion.

Koh J, Park S Cancer Genomics Proteomics. 2024; 22(1):127-135.

PMID: 39730174 PMC: 11696326. DOI: 10.21873/cgp.20493.

Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytes.

James C, Lewis R, Witt A, Carter C, Rais N, Wang X Tumour Virus Res. 2024; 19:200302.

PMID: 39667669 PMC: 11699615. DOI: 10.1016/j.tvr.2024.200302.

References

Markowitz L, Dunne E, Saraiya M, Lawson H, Chesson H, Unger E . Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007; 56(RR-2):1-24. View

zur Hausen H . Papillomavirus infections--a major cause of human cancers. Biochim Biophys Acta. 1996; 1288(2):F55-78. DOI: 10.1016/0304-419x(96)00020-0. View

Parkin D, Bray F . Chapter 2: The burden of HPV-related cancers. Vaccine. 2006; 24 Suppl 3:S3/11-25. DOI: 10.1016/j.vaccine.2006.05.111. View

Wilson R, Fehrmann F, Laimins L . Role of the E1--E4 protein in the differentiation-dependent life cycle of human papillomavirus type 31. J Virol. 2005; 79(11):6732-40. PMC: 1112140. DOI: 10.1128/JVI.79.11.6732-6740.2005. View

Crum C, McKeon F . p63 in epithelial survival, germ cell surveillance, and neoplasia. Annu Rev Pathol. 2010; 5:349-71. DOI: 10.1146/annurev-pathol-121808-102117. View

Alcocer-Gonzalez J, Berumen J, Tamez-Guerra R, Bermudez-Morales V, Peralta-Zaragoza O, Hernandez-Pando R . In vivo expression of immunosuppressive cytokines in human papillomavirus-transformed cervical cancer cells. Viral Immunol. 2006; 19(3):481-91. DOI: 10.1089/vim.2006.19.481. View

Ozbun M, Meyers C . Characterization of late gene transcripts expressed during vegetative replication of human papillomavirus type 31b. J Virol. 1997; 71(7):5161-72. PMC: 191751. DOI: 10.1128/JVI.71.7.5161-5172.1997. View

Stubenrauch F, Lim H, Laimins L . Differential requirements for conserved E2 binding sites in the life cycle of oncogenic human papillomavirus type 31. J Virol. 1998; 72(2):1071-7. PMC: 124579. DOI: 10.1128/JVI.72.2.1071-1077.1998. View

Schwartz S . HPV-16 RNA processing. Front Biosci. 2008; 13:5880-91. DOI: 10.2741/3123. View

10.

Peh W, Middleton K, Christensen N, Nicholls P, Egawa K, Sotlar K . Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J Virol. 2002; 76(20):10401-16. PMC: 136551. DOI: 10.1128/jvi.76.20.10401-10416.2002. View

11.

Frattini M, Laimins L . Binding of the human papillomavirus E1 origin-recognition protein is regulated through complex formation with the E2 enhancer-binding protein. Proc Natl Acad Sci U S A. 1994; 91(26):12398-402. PMC: 45445. DOI: 10.1073/pnas.91.26.12398. View

12.

Rincon-Orozco B, Halec G, Rosenberger S, Muschik D, Nindl I, Bachmann A . Epigenetic silencing of interferon-kappa in human papillomavirus type 16-positive cells. Cancer Res. 2009; 69(22):8718-25. DOI: 10.1158/0008-5472.CAN-09-0550. View

13.

Toussaint-Smith E, Donner D, Roman A . Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene. 2004; 23(17):2988-95. DOI: 10.1038/sj.onc.1207442. View

14.

Samuel C . Antiviral actions of interferons. Clin Microbiol Rev. 2001; 14(4):778-809, table of contents. PMC: 89003. DOI: 10.1128/CMR.14.4.778-809.2001. View

15.

Smith-McCune K, Weidner N . Demonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res. 1994; 54(3):800-4. View

16.

Scott M, Nakagawa M, Moscicki A . Cell-mediated immune response to human papillomavirus infection. Clin Diagn Lab Immunol. 2001; 8(2):209-20. PMC: 96039. DOI: 10.1128/CDLI.8.2.209-220.2001. View

17.

Ruesch M, Laimins L . Human papillomavirus oncoproteins alter differentiation-dependent cell cycle exit on suspension in semisolid medium. Virology. 1998; 250(1):19-29. DOI: 10.1006/viro.1998.9359. View

18.

Bedell M, Hudson J, Golub T, Turyk M, Hosken M, Wilbanks G . Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation. J Virol. 1991; 65(5):2254-60. PMC: 240574. DOI: 10.1128/JVI.65.5.2254-2260.1991. View

19.

OBrien P, Campo M . Evasion of host immunity directed by papillomavirus-encoded proteins. Virus Res. 2002; 88(1-2):103-17. DOI: 10.1016/s0168-1702(02)00123-5. View

20.

Thomas J, Hubert W, Ruesch M, Laimins L . Human papillomavirus type 31 oncoproteins E6 and E7 are required for the maintenance of episomes during the viral life cycle in normal human keratinocytes. Proc Natl Acad Sci U S A. 1999; 96(15):8449-54. PMC: 17536. DOI: 10.1073/pnas.96.15.8449. View