HPV-induced host epigenetic reprogramming is lost upon progression to high-grade cervical intraepithelial neoplasia
Raw Text
Search in PubMed
Search in NLM Catalog
Add to Search
.
2023 Jun 1;152(11):2321-2330.
doi: 10.1002/ijc.34477.
Epub 2023 Mar 8.
Chiara Herzog 1 2 ,
Charlotte D Vavourakis 1 2 ,
James E Barrett 1 2 ,
Gerlinde Karbon 3 ,
Andreas Villunger 3 ,
Jiangrong Wang 4 ,
Karin Sundstrom 4 5 ,
Joakim Dillner 5 ,
Martin Widschwendter 1 2 6 7
Expand
Affiliations
1 European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universitat Innsbruck, Hall in Tirol, Tirol, Austria.
2 Institute for Biomedical Aging Research, Universitat Innsbruck, Innsbruck, Tirol, Austria.
3 Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
4 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden.
5 Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden.
6 Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
7 Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, London, UK.
PMID: 36810770
DOI: 10.1002/ijc.34477
Chiara Herzog et al.
Int J Cancer .
2023 .
Show details
Display options
Format
Search in PubMed
Search in NLM Catalog
Add to Search
.
2023 Jun 1;152(11):2321-2330.
doi: 10.1002/ijc.34477.
Epub 2023 Mar 8.
Authors
Chiara Herzog 1 2 ,
Charlotte D Vavourakis 1 2 ,
James E Barrett 1 2 ,
Gerlinde Karbon 3 ,
Andreas Villunger 3 ,
Jiangrong Wang 4 ,
Karin Sundstrom 4 5 ,
Joakim Dillner 5 ,
Martin Widschwendter 1 2 6 7
Affiliations
1 European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universitat Innsbruck, Hall in Tirol, Tirol, Austria.
2 Institute for Biomedical Aging Research, Universitat Innsbruck, Innsbruck, Tirol, Austria.
3 Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
4 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden.
5 Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden.
6 Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
7 Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, London, UK.
PMID: 36810770
DOI: 10.1002/ijc.34477
Cite
Display options
Format
Abstract
The impact of a pathogen on host disease can only be studied in samples covering the entire spectrum of pathogenesis. Persistent oncogenic human papilloma virus (HPV) infection is the most common cause for cervical cancer. Here, we investigate HPV-induced host epigenome-wide changes prior to development of cytological abnormalities. Using cervical sample methylation array data from disease-free women with or without an oncogenic HPV infection, we develop the WID (Women's cancer risk identification)-HPV, a signature reflective of changes in the healthy host epigenome related to high-risk HPV strains (AUC = 0.78, 95% CI: 0.72-0.85, in nondiseased women). Looking at HPV-associated changes across disease development, HPV-infected women with minor cytological alterations (cervical intraepithelial neoplasia grade 1/2, CIN1/2), but surprisingly not those with precancerous changes or invasive cervical cancer (CIN3+), show an increased WID-HPV index, indicating the WID-HPV may reflect a successful viral clearance response absent in progression to cancer. Further investigation revealed the WID-HPV is positively associated with apoptosis (ρ = 0.48; P < .001) and negatively associated with epigenetic replicative age (ρ = -0.43; P < .001). Taken together, our data suggest the WID-HPV captures a clearance response associated with apoptosis of HPV-infected cells. This response may be dampened or lost with increased underlying replicative age of infected cells, resulting in progression to cancer.
Keywords: DNA methylation; apoptosis; cervical cancer; human papillomavirus; replicative aging.
© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
PubMed Disclaimer
Similar articles
The WID-CIN test identifies women with, and at risk of, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer. Barrett JE, Sundstrom K, Jones A, Evans I, Wang J, Herzog C, Dillner J, Widschwendter M. Barrett JE, et al. Genome Med. 2022 Oct 19;14(1):116. doi: 10.1186/s13073-022-01116-9. Genome Med. 2022. PMID: 36258199 Free PMC article.
Molecular progression to cervical precancer, epigenetic switch or sequential model? Nedjai B, Reuter C, Ahmad A, Banwait R, Warman R, Carton J, Boer S, Cuzick J, Lorincz AT. Nedjai B, et al. Int J Cancer. 2018 Oct 1;143(7):1720-1730. doi: 10.1002/ijc.31549. Epub 2018 Jul 3. Int J Cancer. 2018. PMID: 29679470 Free PMC article.
The application of human papilloma virus genotyping for the identification of neoplasm lesions in the cervix of women with abnormal cytology smears. Ciszek B, Heimrath J, Ciszek M. Ciszek B, et al. Adv Clin Exp Med. 2012 Nov-Dec;21(6):759-66. Adv Clin Exp Med. 2012. PMID: 23457134
Epidemiology of cervical intraepithelial neoplasia: the role of human papillomavirus. Cox JT. Cox JT. Baillieres Clin Obstet Gynaecol. 1995 Mar;9(1):1-37. doi: 10.1016/s0950-3552(05)80357-8. Baillieres Clin Obstet Gynaecol. 1995. PMID: 7600720 Review.
[Epidemiology of cervical papillomavirus infections. Recent knowledge]. Mougin C, Dalstein V, Pretet JL, Gay C, Schaal JP, Riethmuller D. Mougin C, et al. Presse Med. 2001 Jun 9;30(20):1017-23. Presse Med. 2001. PMID: 11433694 Review. French.
See all similar articles
References
REFERENCES
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249.
Sundstrom K, Eloranta S, Sparen P, et al. Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix. Cancer Epidemiol Prev Biomark. 2010;19:2469-2478.
Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382:889-899.
McBride AA, Warburton A. The role of integration in oncogenic progression of HPV-associated cancers. PLoS Pathog. 2017;13:e1006211.
Fiano V, Trevisan M, Fasanelli F, et al. Methylation in host and viral genes as marker of aggressiveness in cervical lesions: analysis in 543 unscreened women. Gynecol Oncol. 2018;151:319-326.
Publication types
Research Support, Non-U.S. Gov't Actions Search in PubMed Search in MeSH Add to Search
MeSH terms
Cervix Uteri / pathology Actions Search in PubMed Search in MeSH Add to Search
Epigenesis, Genetic Actions Search in PubMed Search in MeSH Add to Search
Female Actions Search in PubMed Search in MeSH Add to Search
Humans Actions Search in PubMed Search in MeSH Add to Search
Papillomaviridae / genetics Actions Search in PubMed Search in MeSH Add to Search
Papillomavirus Infections* / complications Actions Search in PubMed Search in MeSH Add to Search
Papillomavirus Infections* / genetics Actions Search in PubMed Search in MeSH Add to Search
Papillomavirus Infections* / pathology Actions Search in PubMed Search in MeSH Add to Search
Uterine Cervical Dysplasia* Actions Search in PubMed Search in MeSH Add to Search
Uterine Cervical Neoplasms* Actions Search in PubMed Search in MeSH Add to Search
Related information
GEO DataSets
MedGen
Related Project
Grants and funding
742432/ERC_/European Research Council/International
LinkOut - more resources
Full Text Sources Ovid Technologies, Inc. Wiley
Medical Genetic Alliance International Agency for Research on Cancer - Screening Group MedlinePlus Consumer Health Information MedlinePlus Health Information
Single Line Text
Search in PubMed. Search in NLM Catalog. Add to Search. . 2023 Jun 1;152(11):2321-2330. doi: 10.1002/ijc.34477. Epub 2023 Mar 8. Chiara Herzog 1 2 , Charlotte D Vavourakis 1 2 , James E Barrett 1 2 , Gerlinde Karbon 3 , Andreas Villunger 3 , Jiangrong Wang 4 , Karin Sundstrom 4 5 , Joakim Dillner 5 , Martin Widschwendter 1 2 6 7. Expand. Affiliations. 1 European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universitat Innsbruck, Hall in Tirol, Tirol, Austria. 2 Institute for Biomedical Aging Research, Universitat Innsbruck, Innsbruck, Tirol, Austria. 3 Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria. 4 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden. 5 Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden. 6 Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 7 Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, London, UK. PMID: 36810770. DOI: 10.1002/ijc.34477. Chiara Herzog et al. Int J Cancer . 2023 . Show details. Display options. Format. Search in PubMed. Search in NLM Catalog. Add to Search. . 2023 Jun 1;152(11):2321-2330. doi: 10.1002/ijc.34477. Epub 2023 Mar 8. Authors. Chiara Herzog 1 2 , Charlotte D Vavourakis 1 2 , James E Barrett 1 2 , Gerlinde Karbon 3 , Andreas Villunger 3 , Jiangrong Wang 4 , Karin Sundstrom 4 5 , Joakim Dillner 5 , Martin Widschwendter 1 2 6 7. Affiliations. 1 European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universitat Innsbruck, Hall in Tirol, Tirol, Austria. 2 Institute for Biomedical Aging Research, Universitat Innsbruck, Innsbruck, Tirol, Austria. 3 Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria. 4 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden. 5 Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden. 6 Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 7 Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, London, UK. PMID: 36810770. DOI: 10.1002/ijc.34477. Cite. Display options. Format. Abstract. The impact of a pathogen on host disease can only be studied in samples covering the entire spectrum of pathogenesis. Persistent oncogenic human papilloma virus (HPV) infection is the most common cause for cervical cancer. Here, we investigate HPV-induced host epigenome-wide changes prior to development of cytological abnormalities. Using cervical sample methylation array data from disease-free women with or without an oncogenic HPV infection, we develop the WID (Women's cancer risk identification)-HPV, a signature reflective of changes in the healthy host epigenome related to high-risk HPV strains (AUC = 0.78, 95% CI: 0.72-0.85, in nondiseased women). Looking at HPV-associated changes across disease development, HPV-infected women with minor cytological alterations (cervical intraepithelial neoplasia grade 1/2, CIN1/2), but surprisingly not those with precancerous changes or invasive cervical cancer (CIN3+), show an increased WID-HPV index, indicating the WID-HPV may reflect a successful viral clearance response absent in progression to cancer. Further investigation revealed the WID-HPV is positively associated with apoptosis (ρ = 0.48; P < .001) and negatively associated with epigenetic replicative age (ρ = -0.43; P < .001). Taken together, our data suggest the WID-HPV captures a clearance response associated with apoptosis of HPV-infected cells. This response may be dampened or lost with increased underlying replicative age of infected cells, resulting in progression to cancer. Keywords: DNA methylation; apoptosis; cervical cancer; human papillomavirus; replicative aging. © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. PubMed Disclaimer. Similar articles. The WID-CIN test identifies women with, and at risk of, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer. Barrett JE, Sundstrom K, Jones A, Evans I, Wang J, Herzog C, Dillner J, Widschwendter M. Barrett JE, et al. Genome Med. 2022 Oct 19;14(1):116. doi: 10.1186/s13073-022-01116-9. Genome Med. 2022. PMID: 36258199 Free PMC article. Molecular progression to cervical precancer, epigenetic switch or sequential model? Nedjai B, Reuter C, Ahmad A, Banwait R, Warman R, Carton J, Boer S, Cuzick J, Lorincz AT. Nedjai B, et al. Int J Cancer. 2018 Oct 1;143(7):1720-1730. doi: 10.1002/ijc.31549. Epub 2018 Jul 3. Int J Cancer. 2018. PMID: 29679470 Free PMC article. The application of human papilloma virus genotyping for the identification of neoplasm lesions in the cervix of women with abnormal cytology smears. Ciszek B, Heimrath J, Ciszek M. Ciszek B, et al. Adv Clin Exp Med. 2012 Nov-Dec;21(6):759-66. Adv Clin Exp Med. 2012. PMID: 23457134. Epidemiology of cervical intraepithelial neoplasia: the role of human papillomavirus. Cox JT. Cox JT. Baillieres Clin Obstet Gynaecol. 1995 Mar;9(1):1-37. doi: 10.1016/s0950-3552(05)80357-8. Baillieres Clin Obstet Gynaecol. 1995. PMID: 7600720 Review. [Epidemiology of cervical papillomavirus infections. Recent knowledge]. Mougin C, Dalstein V, Pretet JL, Gay C, Schaal JP, Riethmuller D. Mougin C, et al. Presse Med. 2001 Jun 9;30(20):1017-23. Presse Med. 2001. PMID: 11433694 Review. French. See all similar articles. References. REFERENCES. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249. Sundstrom K, Eloranta S, Sparen P, et al. Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix. Cancer Epidemiol Prev Biomark. 2010;19:2469-2478. Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382:889-899. McBride AA, Warburton A. The role of integration in oncogenic progression of HPV-associated cancers. PLoS Pathog. 2017;13:e1006211. Fiano V, Trevisan M, Fasanelli F, et al. Methylation in host and viral genes as marker of aggressiveness in cervical lesions: analysis in 543 unscreened women. Gynecol Oncol. 2018;151:319-326. Publication types. Research Support, Non-U.S. Gov't Actions Search in PubMed Search in MeSH Add to Search. MeSH terms. Cervix Uteri / pathology Actions Search in PubMed Search in MeSH Add to Search. Epigenesis, Genetic Actions Search in PubMed Search in MeSH Add to Search. Female Actions Search in PubMed Search in MeSH Add to Search. Humans Actions Search in PubMed Search in MeSH Add to Search. Papillomaviridae / genetics Actions Search in PubMed Search in MeSH Add to Search. Papillomavirus Infections* / complications Actions Search in PubMed Search in MeSH Add to Search. Papillomavirus Infections* / genetics Actions Search in PubMed Search in MeSH Add to Search. Papillomavirus Infections* / pathology Actions Search in PubMed Search in MeSH Add to Search. Uterine Cervical Dysplasia* Actions Search in PubMed Search in MeSH Add to Search. Uterine Cervical Neoplasms* Actions Search in PubMed Search in MeSH Add to Search. Related information. GEO DataSets. MedGen. Related Project. Grants and funding. 742432/ERC_/European Research Council/International. LinkOut - more resources. Full Text Sources Ovid Technologies, Inc. Wiley. Medical Genetic Alliance International Agency for Research on Cancer - Screening Group MedlinePlus Consumer Health Information MedlinePlus Health Information.