Abstract
High-risk human papillomaviruses (HPV) cause 5% of all human cancers and are primary etiologic agents of cervical, anal, and oropharyngeal cancer. HPV infection is necessary, but not sufficient per se to produce cancer: additional changes must occur that transform HPV-infected cells to malignancy. The HPV oncoproteins E6 and E7 immortalize human keratinocytes, cervical cells, and fibroblasts in culture. Each oncoprotein interacts with a variety of cellular binding partners; most important for transformation are E6 and E7’s interactions with p53 and RB (respectively) which lead to degradation of p53 and RB through the ubiquitin pathway. Inactivation of p53 and RB leads to inactivation of pivotal cell cycle checkpoints, thereby stimulating cell proliferation and allowing cell division to occur independently of the presence of DNA damage, replicative stress, and other such insults, leading to genome instability. Continuous expression of E6/E7 drives the proliferation and progression of most HPV-mediated cancers of the cervix and a substantial fraction of those of the oropharynx. However, at both cancer sites, “HPV-inactive” tumors that contain HPV DNA, but do not express E6/E7 arise. We propose that these HPV-inactive cancers begin as HPV-driven lesions, but lose E6/E7 expression at some point during progression. We have recently shown that p53 deletion in HPV-immortalized, premalignant cells allows for the emergence of cell populations that no longer express E6/E7. These findings corroborate the notion of a pivotal role of p53 in the context of HPV-mediated transformation, both at the initiation and progression stages of cancer development.
Similar content being viewed by others
References
Abboodi, F., Buckhaults, P., Altomare, D., Liu, C., Hosseinipour, M., Banister, C. E., Creek, K. E., & Pirisi, L. (2021). HPV-inactive cell populations arise from HPV16-transformed human keratinocytes after p53 knockout. Virology, 554, 9–16. https://doi.org/10.1016/j.virol.2020.12.005
Abboodi, F. F. (2016). Tumor Suppressor p53 Response To UV Light In Normal Human Keratinocyte Strains From Different Individuals. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/3427
Adelstein, D. J., Ridge, J. A., Gillison, M. L., Chaturvedi, A. K., D'Souza, G., Gravitt, P. et al. (2009). Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9–10, 2008, Washington, D.C. Head & neck, 31(11), 1393–1422. https://doi.org/10.1002/hed.21269
Akerman, G. S., Tolleson, W. H., Brown, K. L., Zyzak, L. L., Mourateva, E., Engin, T. S., Basaraba, A., Coker, A. L., Creek, K. E., & Pirisi, L. (2001). Human papillomavirus type 16 E6 and E7 cooperate to increase epidermal growth factor receptor (EGFR) mRNA levels, overcoming mechanisms by which excessive EGFR signaling shortens the life span of normal human keratinocytes. Cancer Research, 61, 3837–3843
Alexandrov, L. B., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A., Behjati, S., Biankin, A. V., Bignell, G. R., Bolli, N., Borg, A., Børresen-Dale, A. L., Boyault, S., Burkhardt, B., Butler, A. P., Caldas, C., Davies, H. R., Desmedt, C., Eils, R., Eyfjörd, J. E., Foekens, J. A., … Stratton, M. R. (2013). Signatures of mutational processes in human cancer. Nature, 500(7463), 415–421. https://doi.org/10.1038/nature12477
Antonsson, A., Forslund, O., Ekberg, H., Sterner, G., & Hansson, B. G. (2000). The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses. Journal of Virology, 74(24), 11636–11641. https://doi.org/10.1128/jvi.74.24.11636-11641.2000
Antonsson, A., & McMillan, N. A. (2006). Papillomavirus in healthy skin of Australian animals. Journal of General Virology, 87(Pt 11), 3195–3200
Arenz, A., Ziemann, F., Mayer, C., Wittig, A., Dreffke, K., Preising, S., Wagner, S., Klussmann, J. P., Engenhart-Cabillic, R., & Wittekindt, C. (2014). Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al], 190(9), 839–846. https://doi.org/10.1007/s00066-014-0605-5
Aydin, I., Villalonga-Planells, R., Greune, L., Bronnimann, M. P., Calton, C. M., Becker, M., Lai, K. Y., Campos, S. K., Schmidt, M. A., & Schelhaas, M. (2017). A central region in the minor capsid protein of papillomaviruses facilitates viral genome tethering and membrane penetration for mitotic nuclear entry. PLoS Pathogens, 13, e1006308
Baldwin, A., Pirisi, L., & Creek, K. E. (2004). NFI-Ski interactions mediate transforming growth factor beta modulation of human papillomavirus type 16 early gene expression. Journal of Virology, 78(8), 3953–3964. https://doi.org/10.1128/jvi.78.8.3953-3964.2004
Banister, C. E., Liu, C., Pirisi, L., Creek, K. E., & Buckhaults, P. J. (2017). Identification and characterization of HPV-independent cervical cancers. Oncotarget, 8(8), 13375–13386. https://doi.org/10.18632/oncotarget.14533
Beachler, D. C., Weber, K. M., Margolick, J. B., Strickler, H. D., Cranston, R. D., Burk, R. D., Wiley, D. J., Minkoff, H., Reddy, S., Stammer, E. E., Gillison, M. L., & D’Souza, G. (2012). Risk factors for oral HPV infection among a high prevalence population of HIV-positive and at-risk HIV-negative adults. Cancer Epidemiology, Biomarkers & Prevention, 21(1), 122–133. https://doi.org/10.1158/1055-9965.EPI-11-0734
Benedetti, F., Curreli, S., Gallo, R. C., & Zella, D. (2021). Tampering of viruses and bacteria with host DNA repair: Implications for cellular transformation. Cancers, 13(2), 241. https://doi.org/10.3390/cancers13020241
Berman, T. A., & Schiller, J. T. (2017). Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases. Cancer, 123(12), 2219–2229. https://doi.org/10.1002/cncr.30588
Bernard, H. U., Burk, R. D., Chen, Z., van Doorslaer, K., & zur Hausen, H., de Villiers, E. M. . (2010). Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology, 401(1), 70–79. https://doi.org/10.1016/j.virol.2010.02.002
Bettampadi, D., Sirak, B. A., Abrahamsen, M. E., Reich, R. R., Villa, L. L., Ponce, E. L., & Giuliano, A. R. (2020). Factors associated with persistence and clearance of high-risk oral HPV among participants in the HPV Infection in Men (HIM) study. Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America, ciaa1701. Advance online publication. https://doi.org/10.1093/cid/ciaa1701
Bhatla, N., Berek, J. S., Cuello Fredes, M., Denny, L. A., Grenman, S., Karunaratne, K., et al. (2019). Revised FIGO staging for carcinoma of the cervix uteri. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics, 145(1), 129–135. https://doi.org/10.1002/ijgo.12749
Bheda, A., Creek, K. E., & Pirisi, L. (2008). Loss of p53 induces epidermal growth factor receptor promoter activity in normal human keratinocytes. Oncogene, 27(31), 4315–4323. https://doi.org/10.1038/onc.2008.65
Blackford, A. N., & Jackson, S. P. (2017). ATM, ATR, and DNA-PK: The trinity at the heart of the DNA damage response. Molecular Cell, 66(6), 801–817. https://doi.org/10.1016/j.molcel.2017.05.015
Blevins, M. A., Towers, C. G., Patrick, A. N., Zhao, R., & Ford, H. L. (2015). The SIX1-EYA transcriptional complex as a therapeutic target in cancer. Expert Opinion on Therapeutic Targets, 19(2), 213–225. https://doi.org/10.1517/14728222.2014.978860
Blomberg, I., & Hoffmann, I. (1999). Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases. Molecular and Cellular Biology, 19(9), 6183–6194. https://doi.org/10.1128/mcb.19.9.6183
Bonner, J. A., Harari, P. M., Giralt, J., Azarnia, N., Shin, D. M., Cohen, , et al. (2006). Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. The New England Journal of Medicine, 354(6), 567–578. https://doi.org/10.1056/NEJMoa053422
Borger, D. R., Mi, Y., Geslani, G., Zyzak, L. L., Batova, A., Engin, T. S., Pirisi, L., & Creek, K. E. (2000). Retinoic acid resistance at late stages of human papillomavirus type 16-mediated transformation of human keratinocytes arises despite intact retinoid signaling and is due to a loss of sensitivity to transforming growth factor-beta. Virology, 270(2), 397–407. https://doi.org/10.1006/viro.2000.0282
Boyer, S. N., Wazer, D. E., & Band, V. (1996). E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. Cancer Research, 56(20), 4620–4624
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians, 68(6), 394–424. https://doi.org/https://doi.org/10.3322/caac.21492
Bruni, L., Diaz, M., Castellsagué, X., Ferrer, E., Bosch, F. X., & de Sanjosé, S. (2010). Cervical human papillomavirus prevalence in 5 continents: Meta-analysis of 1 million women with normal cytological findings. The Journal of Infectious Diseases, 202(12), 1789–1799. https://doi.org/10.1086/657321
Burley, M., Roberts, S., & Parish, J. L. (2020). Epigenetic regulation of human papillomavirus transcription in the productive virus life cycle. Semin Immunopathol, 42, 159–171. https://doi.org/10.1007/s00281-019-00773-0
Calton, C. M., Bronnimann, M. P., Manson, A. R., Li, S., Chapman, J. A., Suarez-Berumen, M., Williamson, T. R., Molugu, S. K., Bernal, R. A., & Campos, S. K. (2017). Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis. PLoS Pathogens, 13, e1006200
Cancer Genome Atlas Research Network. (2017). Integrated genomic and molecular characterization of cervical cancer. Nature, 543(7645), 378–384. https://doi.org/10.1038/nature21386
Carr A. M. (2000). Cell cycle. Piecing together the p53 puzzle. Science (New York, N.Y.), 287(5459), 1765–1766. https://doi.org/https://doi.org/10.1126/science.287.5459.1765
Chabeda, A., Yanez, R., Lamprecht, R., Meyers, A. E., Rybicki, E. P., & Hitzeroth, I. I. (2018). Therapeutic vaccines for high-risk HPV-associated diseases. Papillomavirus Research (Amsterdam, Netherlands), 5, 46–58. https://doi.org/10.1016/j.pvr.2017.12.006
Chaturvedi, A. K., Engels, E. A., Anderson, W. F., & Gillison, M. L. (2008). Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 26(4), 612–619. https://doi.org/10.1200/JCO.2007.14.1713
Chen, D., Juko-Pecirep, I., Hammer, J., Ivansson, E., Enroth, S., Gustavsson, I., Feuk, L., Magnusson, P. K., McKay, J. D., Wilander, E., & Gyllensten, U. (2013). Genome-wide association study of susceptibility loci for cervical cancer. Journal of the National Cancer Institute, 105(9), 624–633. https://doi.org/10.1093/jnci/djt051
Cheng, S., Schmidt-Grimminger, D. C., Murant, T., Broker, T. R., & Chow, L. T. (1995). Differentiation-dependent up-regulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes. Genes & Development, 9(19), 2335–2349. https://doi.org/10.1101/gad.9.19.2335
Christensen, K. L., Patrick, A. N., McCoy, E. L., & Ford, H. L. (2008). The six family of homeobox genes in development and cancer. Advances in Cancer Research, 101, 93–126. https://doi.org/10.1016/S0065-230X(08)00405-3
Chung, C., & Gillison, M. (2009). Human papillomavirus in head and neck cancer: Its role in pathogenesis and clinical implications. Clinical Cancer Research, 15, 6758–6762. https://doi.org/10.1158/1078-0432.CCR-09-0784
Coletta, R. D., Christensen, K. L., Micalizzi, D. S., Jedlicka, P., Varella-Garcia, M., & Ford, H. L. (2008). Six1 overexpression in mammary cells induces genomic instability and is sufficient for malignant transformation. Cancer Research, 68(7), 2204–2213. https://doi.org/10.1158/0008-5472.CAN-07-3141
Coletta, R. D., McCoy, E. L., Burns, V., Kawakami, K., McManaman, J. L., Wysolmerski, J. J., & Ford, H. L. (2010). Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis. BMC Developmental Biology, 10, 4. https://doi.org/10.1186/1471-213X-10-4
Creek, K. E., Geslani, G., Batova, A., & Pirisi, L. (1995). Progressive loss of sensitivity to growth control by retinoic acid and transforming growth factor-beta at late stages of human papillomavirus type 16-initiated transformation of human keratinocytes. Advances in Experimental Medicine and Biology, 375, 117–135. https://doi.org/10.1007/978-1-4899-0949-7_11
Crook, T., Fisher, C., Masterson, P., & Vousden, K. (1994). Modulation of transcriptional regulatory properties of p53 by HPV E6. Oncogene, 9, 1225–1230
Das Ghosh, D., Mukhopadhyay, I., Bhattacharya, A., Roy Chowdhury, R., Mandal, N. R., Roy, S., & Sengupta, S. (2017). Impact of genetic variations and transcriptional alterations of HLA class I genes on cervical cancer pathogenesis. International Journal of Cancer, 140(11), 2498–2508. https://doi.org/10.1002/ijc.30681
de Villiers, E. M. (2013). Cross-roads in the classification of papillomaviruses. Virology, 445(1–2), 2–10. https://doi.org/10.1016/j.virol.2013.04.023
DeGregori, J., & Johnson, D. G. (2006). Distinct and Overlapping Roles for E2F Family Members in Transcription, Proliferation and Apoptosis. Current Molecular Medicine, 6(7), 739–748. https://doi.org/10.2174/1566524010606070739
Delury, C. P., Marsh, E. K., James, C. D., Boon, S. S., Banks, L., Knight, G. L., & Roberts, S. (2013). The role of protein kinase A regulation of the E6 PDZ-binding domain during the differentiation-dependent life cycle of human papillomavirus type 18. Journal of Virology, 87, 9463–9472. https://doi.org/10.1128/JVI.01234-13
Delva, N. C. (2015). Tp53 and Hras Influence on HPV16 E7 Expression in HPV16-Transformed Human Keratinocytes. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/3090
DiMaio, D., & Mattoon, D. (2001). Mechanisms of cell transformation by papillomavirus E5 proteins. Oncogene, 20(54), 7866–7873. https://doi.org/10.1038/sj.onc.1204915
DiMaio, D., & Petti, L. M. (2013). The E5 proteins. Virology, 445(1–2), 99–114. https://doi.org/10.1016/j.virol.2013.05.006
DiPaolo, J. A., Popescu, N. C., Ablashi, D. V., Lusso, P., Zimonjic, D. B., & Woodworth, C. D. (1994). Multistage carcinogenesis utilizing human genital cells and human papillomaviruses. Toxicology Letters, 72(1–3), 7–11. https://doi.org/10.1016/0378-4274(94)90004-3
DiPaolo, J. A., Woodworth, C. D., Popescu, N. C., Koval, D. L., Lopez, J. V., & Doniger, J. (1990). HSV-2-induced tumorigenicity in HPV16-immortalized human genital keratinocytes. Virology, 177, 777–779. https://doi.org/10.1016/0042-6822(90)90548-6
DiPaolo, J. A., Woodworth, C. D., Popescu, N. C., Notario, V., & Doniger, J. (1989). Induction of human cervical squamous cell carcinoma by sequential transfection with human papillomavirus 16 DNA and viral Harvey ras. Oncogene, 4, 395–399
Diskin, B., Adam, S., Cassini, M. F., Sanchez, G., Liria, M., Aykut, B., Buttar, C., Li, E., Sundberg, B., Salas, R. D., Chen, R., Wang, J., Kim, M., Farooq, M. S., Nguy, S., Fedele, C., Tang, K. H., Chen, T., Wang, W., … Miller, G. (2020). PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer. Nature Immunology, 21(4), 442–454. https://doi.org/10.1038/s41590-020-0620-x
Donalisio, M., Cagno, V., Vallino, M., Moro, G. E., Arslanoglu, S., Tonetto, P., et al. (2014). Inactivation of high-risk human papillomaviruses by Holder pasteurization: Implications for donor human milk banking. Journal of Perinatal Medicine, 42(1), 1–8. https://doi.org/10.1515/jpm-2013-0200
Doorbar, J. (2013). The E4 protein; structure, function and patterns of expression. Virology, 445(1–2), 80–98. https://doi.org/10.1016/j.virol.2013.07.008
Doorbar, J., Egawa, N., Griffin, H., Kranjec, C., Murakami, I. (2015). Human papillomavirus molecular biology and disease association. Reviews in Medical Virology, 25 Suppl 1(Suppl Suppl 1), 2–23. https://doi.org/10.1002/rmv.1822
Doorbar J. (2006). Molecular biology of human papillomavirus infection and cervical cancer. Clinical Science (London, England: 1979), 110(5), 525–541. https://doi.org/10.1042/CS20050369
Dreer, M., van de Poel, S., & Stubenrauch, F. (2017). Control of viral replication and transcription by the papillomavirus E8^E2 protein. Virus Research, 231, 96–102. https://doi.org/10.1016/j.virusres.2016.11.005
Duensing, A., Spardy, N., Chatterjee, P., Zheng, L., Parry, J., Cuevas, R., Korzeniewski, N., & Duensing, S. (2009). Centrosome overduplication, chromosomal instability, and human papillomavirus oncoproteins. Environmental and Molecular Mutagenesis, 50, 741–747. https://doi.org/10.1002/em.20478
el-Deiry, W. S. (1998). Regulation of p53 downstream genes. Seminars in Cancer Biology, 8(5), 345–357. https://doi.org/10.1006/scbi.1998.0097
Ferris, R. L., Blumenschein, G., Jr., Fayette, J., Guigay, J., Colevas, A. D., Licitra, L., et al. (2016). Nivolumab for recurrent squamous-cell carcinoma of the head and neck. The New England Journal of Medicine, 375(19), 1856–1867. https://doi.org/10.1056/NEJMoa1602252
Funk, J. O., Waga, S., Harry, J. B., Espling, E., Stillman, B., & Galloway, D. A. (1997). Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein. Genes & Development, 11, 2090–2100. https://doi.org/10.1101/gad.11.16.2090
Gage, J. R., Meyers, C., & Wettstein, F. O. (1990). The E7 proteins of the nononcogenic human papillomavirus type 6b (HPV-6b) and of the oncogenic HPV-16 differ in retinoblastoma protein binding and other properties. Journal of Virology, 64(2), 723–730. https://doi.org/10.1128/JVI.64.2.723-730.1990
Gillison, M. L., Chaturvedi, A. K., & Lowy, D. R. (2008). HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer, 113(10 Suppl), 3036–3046. https://doi.org/10.1002/cncr.23764
Goodman, A. M., Kato, S., Chattopadhyay, R., Okamura, R., Saunders, I. M., Montesion, M., Frampton, G. M., Miller, V. A., Daniels, G. A., & Kurzrock, R. (2019). Phenotypic and genomic determinants of immunotherapy response associated with squamousness. Cancer immunology research, 7(6), 866–873. https://doi.org/10.1158/2326-6066.CIR-18-0716
Graves, C., Abboodi, F., Tomar, S., Wells, J., & Pirisi, L. (2014). The translational significance of epithelial mesenchymal transition in head and neck cancer. Clinical and Translational Medicine, 3, 39–52. https://doi.org/10.1186/s40169-014-0039
Griffiths, P. (1999). Time to consider the concept of a commensal virus? Reviews in medical virology, 9(2), 73–74. https://doi.org/10.1002/(sici)1099-1654(199904/06)9:2%3c73::aid-rmv254%3e3.0.co;2-5
Guihard, S., Ramolu, L., Macabre, C., Wasylyk, B., Noël, G., Abecassis, J., & Jung, A. C. (2012). The NEDD8 conjugation pathway regulates p53 transcriptional activity and head and neck cancer cell sensitivity to ionizing radiation. International Journal of Oncology, 41(4), 1531–1540. https://doi.org/10.3892/ijo.2012.1584
Gupta, S., Kumar, P., & Das, B. C. (2018). HPV: Molecular pathways and targets. Current Problems in Cancer, 42(2), 161–174. https://doi.org/10.1016/j.currproblcancer.2018.03.003
Halbert, C. L., Demers, G. W., & Galloway, D. A. (1991). The E7 gene of human papillomavirus type 16 is sufficient for immortalization of human epithelial cells. Journal of Virology, 65(1), 473–478. https://doi.org/10.1128/JVI.65.1.473-478.1991
Hammer, A., de Koning, M. N., Blaakaer, J., Steiniche, T., Doorbar, J., Griffin, H., Mejlgaard, E., Svanholm, H., Quint, W. G., & Gravitt, P. E. (2019). Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans. Papillomavirus Res., 7, 82–87
Hawley-Nelson, P., Vousden, K. H., Hubbert, N. L., Lowy, D. R., & Schiller, J. T. (1989). HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. The EMBO Journal, 8(12), 3905–3910
He, W., Staples, D., Smith, C., & Fisher, C. (2003). Direct activation of cyclin-dependent kinase 2 by human papillomavirus E7. Journal of Virology, 77(19), 10566–10574. https://doi.org/10.1128/jvi.77.19.10566-10574.2003
Herbst, R. S., Soria, J. C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., Kohrt, H. E., Horn, L., Lawrence, D. P., Rost, S., Leabman, M., Xiao, Y., Mokatrin, A., Koeppen, H., Hegde, P. S., … Hodi, F. S. (2014). Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 515(7528), 563–567. https://doi.org/10.1038/nature14011
Hosseinipour, M., Wan, F., Altomare, D., Creek, K. E., & Pirisi, L. (2019). HPV16-transformed human keratinocytes depend on SIX1 expression for proliferation and HPV E6/E7 gene expression. Virology, 537, 20–30. https://doi.org/10.1016/j.virol.2019.08.009
Howie, H. L., Katzenellenbogen, R. A., & Galloway, D. A. (2009). Papillomavirus E6 proteins. Virology, 384(2), 324–334. https://doi.org/10.1016/j.virol.2008.11.017
Hu, Z., Zhu, D., Wang, W., Li, W., Jia, W., Zeng, X., et al. (2015). Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism. Nature Genetics, 47(2), 158–163. https://doi.org/10.1038/ng.3178
Huang, P. S., Patrick, D. R., Edwards, G., Goodhart, P. J., Huber, H. E., Miles, L., Garsky, V. M., Oliff, A., & Heimbrook, D. C. (1993). Protein domains governing interactions between E2F, the retinoblastoma gene product, and human papillomavirus type 16 E7 protein. Molecular and Cellular Biology, 13(2), 953–960. https://doi.org/10.1128/mcb.13.2.953
Huibregtse, J. M., Scheffner, M., & Howley, P. M. (1991). A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. The EMBO Journal, 10(13), 4129–4135
Ilahi, N. E., & Bhatti, A. (2020). Impact of HPV E5 on viral life cycle via EGFR signaling. Microbial Pathogenesis, 139, 103923. https://doi.org/10.1016/j.micpath.2019.103923
Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., Forman, D. (2011). Global cancer statistics. CA: a Cancer Journal for Clinicians, 61(2), 69–90. https://doi.org/10.3322/caac.20107
Jeon, S., Allen-Hoffmann, B. L., & Lambert, P. F. (1995). Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. Journal of Virology, 69(5), 2989–2997. https://doi.org/10.1128/JVI.69.5.2989-2997.1995
Jones, D. L., Alani, R. M., & Münger, K. (1997). The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of cdk2. Genes & Development, 11(16), 2101–2111. https://doi.org/10.1101/gad.11.16.2101
Kadaja, M., Isok-Paas, H., Laos, T., Ustav, E., & Ustav, M. (2009). Mechanism of genomic instability in cells infected with the high-risk human papillomaviruses. PLoS Pathogens, 5(4), e1000397. https://doi.org/10.1371/journal.ppat.1000397
King, E., Ottensmeier, C., & Thomas, G. (2014). The immune response in HPV+ oropharyngeal cancer. OncoImmunology, 3, e27254
Korzeniewski, N., Spardy, N., Duensing, A., & Duensing, S. (2011). Genomic instability and cancer: lessons learned from human papillomaviruses. Cancer Letters, 305(2), 113–122. https://doi.org/10.1016/j.canlet.2010.10.013
Kowli, S., Velidandla, R., Creek, K. E., & Pirisi, L. (2013). TGF-β regulation of gene expression at early and late stages of HPV16-mediated transformation of human keratinocytes. Virology, 447(1–2), 63–73. https://doi.org/10.1016/j.virol.2013.08.034
Kranjec, C., & Banks, L. (2011). A systematic analysis of human papillomavirus (HPV) E6 PDZ substrates identifies MAGI-1 as a major target of HPV type 16 (HPV-16) and HPV-18 whose loss accompanies disruption of tight junctions. Journal of Virology, 85(4), 1757–1764. https://doi.org/10.1128/JVI.01756-10
Lammens, T., Li, J., Leone, G., & De Veylder, L. (2009). Atypical E2Fs: new players in the E2F transcription factor family. Trends in Cell Biology, 19(3), 111–118. https://doi.org/10.1016/j.tcb.2009.01.002
Lane, D. P. C. (1992). p53, guardian of the genome. Nature, 358(6381), 15–16. https://doi.org/10.1038/358015a0
Lechner, M. S., & Laimins, L. A. (1994). Inhibition of p53 DNA binding by human papillomavirus E6 proteins. Journal of Virology, 68(7), 4262–4273. https://doi.org/10.1128/JVI.68.7.4262-4273.1994
Lee C., Laimins L.A. (2007) The Differentiation-Dependent Life Cycle of Human Papillomaviruses in Keratinocytes. In: Garcea R.L., DiMaio D. (eds) The Papillomaviruses. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-36523-7_4
De Leo, A., Calderon, A., & Lieberman, P. M. (2020). Control of viral latency by episome maintenance proteins. Trends in Microbiology, 28, 150–162. https://doi.org/10.1016/j.tim.2019.09.002
Licitra, L., Bernier, J., Grandi, C., Merlano, M., Bruzzi, P., & Lefebvre, J. L. (2002). Cancer of the oropharynx. Critical Reviews in Oncology Hematology, 41, 107–122. https://doi.org/10.1016/S1040-8428(01)00129-9
Litwin, T. R., Clarke, M. A., Dean, M., & Wentzensen, N. (2017). Somatic host cell alterations in HPV carcinogenesis. Viruses, 9(8), 206. https://doi.org/10.3390/v9080206
Lowe, S. W., & Lin, A. W. (2000). Apoptosis in cancer. Carcinogenesis, 21(3), 485–495. https://doi.org/10.1093/carcin/21.3.485
Lyons, T., Salih, M., & Tuana, B. (2006). Activating E2Fs mediate transcriptional regulation of human E2F6 repressor. American Journal of Physiology. Cell Physiology, 290, C189-199. https://doi.org/10.1152/ajpcell.00630.2004
Mandal, R., Şenbabaoğlu, Y., Desrichard, A., Havel, J. J., Dalin, M. G., Riaz, N., Lee, K. W., Ganly, I., Hakimi, A. A., Chan, T. A., & Morris, L. G. (2016). The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight, 1(17), e89829. https://doi.org/10.1172/jci.insight.89829
Mantovani, F., & Banks, L. (2001). The human papillomavirus E6 protein and its contribution to malignant progression. Oncogene, 20(54), 7874–7887. https://doi.org/10.1038/sj.onc.1204869
McBride, A. A. (2017). Mechanisms and strategies of papillomavirus replication. Biological Chemistry, 398, 919–927
McBride, A. A., & Warburton, A. (2017). The role of integration in oncogenic progression of HPV-associated cancers. PLoS Pathogens, 13, e1006211
McCredie, M. R., Sharples, K. J., Paul, C., Baranyai, J., Medley, G., Jones, R. W., & Skegg, D. C. (2008). Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: A retrospective cohort study. The Lancet. Oncology, 9(5), 425–434. https://doi.org/10.1016/S1470-2045(08)70103-7
McLaughlin-Drubin, M. E., Huh, K. W., & Münger, K. (2008). Human papillomavirus type 16 E7 oncoprotein associates with E2F6. Journal of Virology, 82(17), 8695–8705. https://doi.org/10.1128/JVI.00579-08
McLaughlin-Drubin, M. E., & Münger, K. (2009). The human papillomavirus E7 oncoprotein. Virology, 384(2), 335–344. https://doi.org/10.1016/j.virol.2008.10.006
Meek, D. W. (1999). Mechanisms of switching on p53: A role for covalent modification? Oncogene, 18(53), 7666–7675. https://doi.org/10.1038/sj.onc.1202951
Mi, Y., Borger, D. R., Fernandes, P. R., Pirisi, L., & Creek, K. E. (2000). Loss of transforming growth factor-beta (TGF-beta) receptor type I mediates TGF-beta resistance in human papillomavirus type 16-transformed human keratinocytes at late stages of in vitro progression. Virology, 270(2), 408–416. https://doi.org/10.1006/viro.2000.0283
Micalizzi, D. S., Christensen, K. L., Jedlicka, P., Coletta, R. D., Barón, A. E., Harrell, J. C., Horwitz, K. B., Billheimer, D., Heichman, K. A., Welm, A. L., Schiemann, W. P., & Ford, H. L. (2009). The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-beta signaling. The Journal of Clinical Investigation, 119(9), 2678–2690. https://doi.org/10.1172/JCI37815
Del Mistro, A., Baboci, L., Frayle-Salamanca, H., Trevisan, R., Bergamo, E., Lignitto, L., et al. (2012). Oral human papillomavirus and human herpesvirus-8 infections among human immunodeficiency virus type 1-infected men and women in Italy. Sexually Transmitted Diseases, 39(11), 894–898. https://doi.org/10.1097/OLQ.0b013e31826ef2da
Moody, C. A., & Laimins, L. A. (2010). Human papillomavirus oncoproteins: pathways to transformation. Nature Reviews. Cancer, 10(8), 550–560. https://doi.org/10.1038/nrc2886
Morgan, I. M., DiNardo, L. J., & Windle, B. (2017). Integration of human papillomavirus genomes in head and neck cancer: Is it time to consider a paradigm shift? Viruses, 9, 208
Moscicki, A. B., Schiffman, M., Burchell, A., Albero, G., Giuliano, A. R., Goodman, M. T., Kjaer, S. K., & Palefsky, J. (2012). Updating the natural history of human papillomavirus and anogenital cancers. Vaccine, 30 Suppl 5(0 5), F24–F33. https://doi.org/10.1016/j.vaccine.2012.05.089
Münger, K., Werness, B. A., Dyson, N., Phelps, W. C., Harlow, E., & Howley, P. M. (1989). Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. The EMBO Journal, 8(13), 4099–4105
Neveu, G., Cassonnet, P., Vidalain, P. O., et al. (2012). Comparative analysis of virus-host interactomes with a mammalian high-throughput protein complementation assay based on Gaussia princeps luciferase. Methods (San Diego, Calif.), 58(4), 349–359. https://doi.org/10.1016/j.ymeth.2012.07.029
Niazi, S., Purohit, M., & Niazi, J. H. (2018). Role of p53 circuitry in tumorigenesis: A brief review. European Journal of Medicinal Chemistry, 158, 7–24. https://doi.org/10.1016/j.ejmech.2018.08.099
Nichols, A. C., Dhaliwal, S. S., Palma, D. A., Basmaji, J., Chapeskie, C., Dowthwaite, S., et al. (2013). Does HPV type affect outcome in oropharyngeal cancer?. Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale, 42(1), 9. https://doi.org/10.1186/1916-0216-42-9
Nicolás, I., Saco, A., Barnadas, E., Marimon, L., Rakislova, N., Fusté, P., Rovirosa, A., Gaba, L., Buñesch, L., Gil-Ibañez, B., Pahisa, J., Díaz-Feijoo, B., Torne, A., Ordi, J., & Del Pino, M. (2020). Prognostic implications of genotyping and p16 immunostaining in HPV-positive tumors of the uterine cervix. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, 33(1), 128–137. https://doi.org/10.1038/s41379-019-0360-3
Ostör, A. G. (1993). Natural history of cervical intraepithelial neoplasia: a critical review. International Journal of Gynecological Pathology: Official Journal of the International Society of Gynecological Pathologists, 12(2), 186–192
Ozbun, M. A. (2019). Extracellular events impacting human papillomavirus infections: Epithelial wounding to cell signaling involved in virus entry. Papillomavirus Research (Amsterdam, Netherlands), 7, 188–192. https://doi.org/10.1016/j.pvr.2019.04.009
Pal, A., & Kundu, R. (2020). Human papillomavirus E6 and E7: The cervical cancer hallmarks and targets for therapy. Frontiers in Microbiology, 10, 3116. https://doi.org/10.3389/fmicb.2019.03116
Parish, J. L., Bean, A. M., Park, R. B., & Androphy, E. J. (2006). ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and viral genome maintenance. Molecular Cell, 24(6), 867–876. https://doi.org/10.1016/j.molcel.2006.11.005
Parkin, D., Bray, F., Ferlay, J., & Pisani, P. (2005). Global cancer statistics, 2002. CA: A Cancer Journal for Clinicians, 55, 74–108. https://doi.org/10.3322/canjclin.55.2.74
Patel, D., Huang, S. M., Baglia, L. A., & McCance, D. J. (1999). The E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300. The EMBO Journal, 18(18), 5061–5072. https://doi.org/10.1093/emboj/18.18.5061
Pauken, K. E., & Wherry, E. J. (2015). Overcoming T-cell exhaustion in infection and cancer. Trends in Immunology, 36(4), 265–276. https://doi.org/10.1016/j.it.2015.02.008
Petca, A., Borislavschi, A., Zvanca, M. E., Petca, R. C., Sandru, F., & Dumitrascu, M. C. (2020). Non-sexual HPV transmission and role of vaccination for a better future (Review). Experimental and Therapeutic Medicine, 20(6), 186. https://doi.org/10.3892/etm.2020.9316
Pirisi, L., Creek, K. E., Doniger, J., & DiPaolo, J. A. (1988). Continuous cell lines with altered growth and differentiation properties originate after transfection of human keratinocytes with human papillomavirus type 16 DNA. Carcinogenesis, 9, 1573–1579. https://doi.org/10.1093/carcin/9.9.1573
Pirisi, L., Yasumoto, S., Feller, M., Doniger, J., & DiPaolo, J. A. (1987). Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA. Journal of Virology, 61, 1061–1066. https://doi.org/10.1128/JVI.61.4.1061-1066.1987
Poirson, J., Biquand, E., Straub, M. L., et al. (2017). Mapping the interactome of HPV E6 and E7 oncoproteins with the ubiquitin-proteasome system. The FEBS Journal, 284(19), 3171–3201. https://doi.org/10.1111/febs.14193
Popa, A., Zhang, W., Harrison, M. S., Goodner, K., Kazakov, T., Goodwin, E. C., Lipovsky, A., Burd, C. G., & DiMaio, D. (2015). Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection. PLoS Pathogens, 11, e1004699. https://doi.org/10.1371/journal.ppat.1004699
Prives, C., & Hall, P. A. (1999). The p53 pathway. The Journal of Pathology, 187(1), 112–126. https://doi.org/10.1002/(SICI)1096-9896(199901)187:1%3c112::AID-PATH250%3e3.0.CO;2-3
Prodromidou, A., Iavazzo, C., Fotiou, A., Psomiadou, V., Douligeris, A., Vorgias, G., & Kalinoglou, N. (2019). Short- and long-term outcomes after abdominal radical trachelectomy versus radical hysterectomy for early stage cervical cancer: A systematic review of the literature and meta-analysis. Archives of Gynecology and Obstetrics, 300(1), 25–31. https://doi.org/10.1007/s00404-019-05176-y
Przybyszewska, J., Zlotogorski, A., & Ramot, Y. (2017). Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate. Journal of the American Academy of Dermatology, 76(6), 1161–1175. https://doi.org/10.1016/j.jaad.2016.12.035
Riley, R. S., June, C. H., Langer, R., & Mitchell, M. J. (2019). Delivery technologies for cancer immunotherapy. Nature reviews. Drug Discovery, 18(3), 175–196. https://doi.org/10.1038/s41573-018-0006-z
Ryu, H. J., Kim, E. K., Heo, S. J., Cho, B. C., Kim, H. R., & Yoon, S. O. (2017). Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma. APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica, 125(11), 974–984. https://doi.org/10.1111/apm.12744
Samstein, R. M., Lee, C. H., Shoushtari, A. N., Hellmann, M. D., Shen, R., Janjigian, Y. Y., Barron, D. A., Zehir, A., Jordan, E. J., Omuro, A., Kaley, T. J., Kendall, S. M., Motzer, R. J., Hakimi, A. A., Voss, M. H., Russo, P., Rosenberg, J., Iyer, G., Bochner, B. H., … Morris, L. (2019). Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nature Genetics, 51(2), 202–206. https://doi.org/10.1038/s41588-018-0312-8
Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J., & Howley, P. M. (1990). The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell, 63(6), 1129–1136. https://doi.org/10.1016/0092-8674(90)90409-8
Schlecht, N. F., Burk, R. D., Adrien, L., Dunne, A., Kawachi, N., Sarta, C., et al. (2007). Gene expression profiles in HPV-infected head and neck cancer. The Journal of Pathology, 213(3), 283–293. https://doi.org/10.1002/path.2227
Schuurman, T., Zilver, S., Samuels, S., Schats, W., Amant, F., van Trommel, N., & Lok, C. (2021). Fertility-sparing surgery in gynecologic cancer: a systematic review. Cancers, 13(5), 1008. https://doi.org/10.3390/cancers13051008
Sedman, S. A., Hubbert, N. L., Vass, W. C., Lowy, D. R., & Schiller, J. T. (1992). Mutant p53 can substitute for human papillomavirus type 16 E6 in immortalization of human keratinocytes but does not have E6-associated trans-activation or transforming activity. Journal of Virology, 66, 4201–4208. https://doi.org/10.1128/JVI.66.7.4201-4208.1992
Serrano, B., Brotons, M., Bosch, F. X., & Bruni, L. (2017). Epidemiology and burden of HPV related disease. Best Practice & Research. Clinical Obstetrics & Gynaecology, 47, 14–26. https://doi.org/10.1016/j.bpobgyn.2017.08.006
Sherr, C. J., & Weber, J. D. (2000). The ARF/p53 pathway. Current Opinion in Genetics & Development, 10(1), 94–99. https://doi.org/10.1016/s0959-437x(99)00038-6
Siegel, R., Naishadham, D., & Jemal, A. (2012). Cancer statistics, 2012. CA: a Cancer Journal for Clinicians, 62(1), 10–29. https://doi.org/10.3322/caac.20138
Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: a Cancer Journal for Clinicians, 70(1), 7–30. https://doi.org/10.3322/caac.21590
Smith, P. P., Friedman, C. L., Bryant, E. M., & McDougall, J. K. (1992). Viral integration and fragile sites in human papillomavirus-immortalized human keratinocyte cell lines. Genes, Chromosomes & Cancer, 5(2), 150–157. https://doi.org/10.1002/gcc.2870050209
Spriggs, C. C., & Laimins, L. A. (2017). Human papillomavirus and the DNA damage response: Exploiting host repair pathways for viral replication. Viruses, 9, 232. https://doi.org/10.3390/v9080232
Stanley, M. A. (2012). Epithelial cell responses to infection with human papillomavirus. Clinical Microbiology Reviews, 25(2), 215–222. https://doi.org/10.1128/CMR.05028-11
Stevaux, O., & Dyson, N. J. (2002). A revised picture of the E2F transcriptional network and RB function. Current Opinion in Cell Biology, 14(6), 684–691. https://doi.org/10.1016/s0955-0674(02)00388-5
Szymonowicz, K. A., & Chen, J. (2020). Biological and clinical aspects of HPV-related cancers. Cancer Biology & Medicine, 17(4), 864–878. https://doi.org/10.20892/j.issn.2095-3941.2020.0370
Tan, J., Zhang, C., & Qian, J. (2011). Expression and significance of Six1 and Ezrin in cervical cancer tissue. Tumour Biology, 32(6), 1241–1247. https://doi.org/10.1007/s13277-011-0228-8
Tewari, K. S., Sill, M. W., Long, H. J., 3rd., Penson, R. T., Huang, H., Ramondetta, L. M., Landrum, L. M., Oaknin, A., Reid, T. J., Leitao, M. M., Michael, H. E., & Monk, B. J. (2014). Improved survival with bevacizumab in advanced cervical cancer. The New England Journal of Medicine, 370(8), 734–743. https://doi.org/10.1056/NEJMoa1309748
Tomar, S., Graves, C. A., Altomare, D., Kowli, S., Kassler, S., Sutkowski, N., Gillespie, M. B., Creek, K. E., & Pirisi, L. (2016). Human papillomavirus status and gene expression profiles of oropharyngeal and oral cancers from European American and African American patients. Head Neck, 38. Suppl, 1, E694-704. https://doi.org/10.1002/hed.24072
Vats, A., Trejo-Cerro, O., Thomas, M., & Banks, L. (2021). Human papillomavirus E6 and E7: What remains?. Tumour virus research, 11, 200213. Advance online publication. https://doi.org/https://doi.org/10.1016/j.tvr.2021.200213
Verhoeven, Y., Quatannens, D., Trinh, X. B., Wouters, A., Smits, E., Lardon, F., De Waele, J., & van Dam, P. A. (2021). Targeting the PD-1 axis with pembrolizumab for recurrent or metastatic cancer of the uterine cervix: A brief update. International Journal of Molecular Sciences, 22(4), 1807. https://doi.org/10.3390/ijms22041807
Vieira, V. C., Leonard, B., White, E. A., Starrett, G. J., Temiz, N. A., Lorenz, L. D., Lee, D., Soares, M. A., Lambert, P. F., Howley, P. M., Harris, R. S. (2014). Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B. mBio, 5(6), e02234–14. https://doi.org/10.1128/mBio.02234-14
Vogelstein, B., Lane, D., & Levine, A. J. (2000). Surfing the p53 network. Nature, 408(6810), 307–310. https://doi.org/10.1038/35042675
Vokes, E. E., Agrawal, N., & Seiwert, T. Y. (2015). HPV-Associated Head and Neck Cancer. Journal of the National Cancer Institute, 107(12), djv344. https://doi.org/10.1093/jnci/djv344
Wan, F., Miao, X., Quraishi, I., Kennedy, V., Creek, K. E., & Pirisi, L. (2008). Gene expression changes during HPV-mediated carcinogenesis: A comparison between an in vitro cell model and cervical cancer. International Journal of Cancer, 123(1), 32–40. https://doi.org/10.1002/ijc.23463
Wang, J., Li, Z., Gao, A., Wen, Q., & Sun, Y. (2019). The prognostic landscape of tumor-infiltrating immune cells in cervical cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 120, 109444. https://doi.org/10.1016/j.biopha.2019.109444
Weinberger, P. M., Merkley, M. A., Khichi, S. S., Lee, J. R., Psyrri, A., Jackson, L. L., & Dynan, W. S. (2010). Human papillomavirus-active head and neck cancer and ethnic health disparities. The Laryngoscope, 120(8), 1531–1537. https://doi.org/10.1002/lary.20984
Weinberger, P. M., Yu, Z., Haffty, B. G., Kowalski, D., Harigopal, M., Brandsma, J., Sasaki, C., Joe, J., Camp, R. L., Rimm, D. L., & Psyrri, A. (2006). Molecular classification identifies a subset of human papillomavirus–associated oropharyngeal cancers with favorable prognosis. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 24(5), 736–747. https://doi.org/10.1200/JCO.2004.00.3335
Westra, W. H., Taube, J. M., Poeta, M. L., Begum, S., Sidransky, D., & Koch, W. M. (2008). Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 14(2), 366–369. https://doi.org/10.1158/1078-0432.CCR-07-1402
Wild, C.P., Weiderpass, E., Stewart, B.W. editors (2020). World Cancer Report: Cancer Research for Cancer Prevention. Lyon, France: International Agency for Research on Cancer. Available from: http://publications.iarc.fr/586. Licence: CC BY-NC-ND 3.0 IGO.
Wirth, L. J. (2016). Cetuximab in human papillomavirus-positive oropharynx carcinoma. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 34(12), 1289–1291. https://doi.org/10.1200/JCO.2015.65.1414
Wise-Draper, T. M., & Wells, S. I. (2008). Papillomavirus E6 and E7 proteins and their cellular targets. Frontiers in Bioscience: A Journal and Virtual Library, 13, 1003–1017. https://doi.org/10.2741/2739
Woappi, Y., Altomare, D., Creek, K. E., & Pirisi, L. (2020). Self-assembling 3D spheroid cultures of human neonatal keratinocytes have enhanced regenerative properties. Stem Cell Research, 49, 102048. https://doi.org/10.1016/j.scr.2020.102048
Woappi, Y., Hosseinipour, M., Creek, K. E., & Pirisi, L. (2018). Stem cell properties of normal human keratinocytes determine transformation responses to human papillomavirus 16 DNA. Journal of Virology, 92(11), e00331-e418. https://doi.org/10.1128/JVI.00331-18
Xu, X., Kelleher, K. F., Liao, J., Creek, K. E., & Pirisi, L. (2000). Unique carboxyl-terminal sequences of wild type and alternatively spliced variant forms of transforming growth factor-alpha precursors mediate specific interactions with ErbB4 and ErbB2. Oncogene, 19(28), 3172–3181. https://doi.org/10.1038/sj.onc.1203645
Xu, X., Liao, J., Creek, K. E., & Pirisi, L. (1999). Human keratinocytes and tumor-derived cell lines express alternatively spliced forms of transforming growth factor-alpha mRNA, encoding precursors lacking carboxyl-terminal valine residues. Oncogene, 18(40), 5554–5562. https://doi.org/10.1038/sj.onc.1203091
Xu, H., Pirisi, L., & Creek, K. E. (2015). Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT. Virology, 474, 144–153. https://doi.org/10.1016/j.virol.2014.10.010
Xu, H., Zhang, Y., Altomare, D., Peña, M. M., Wan, F., Pirisi, L., & Creek, K. E. (2014). Six1 promotes epithelial-mesenchymal transition and malignant conversion in human papillomavirus type 16-immortalized human keratinocytes. Carcinogenesis, 35, 1379–1388. https://doi.org/10.1093/carcin/bgu050
Yang, A., Jeang, J., Cheng, K., Cheng, T., Yang, B., Wu, T. C., & Hung, C. F. (2016). Current state in the development of candidate therapeutic HPV vaccines. Expert Review of Vaccines, 15(8), 989–1007. https://doi.org/10.1586/14760584.2016.1157477
Yilmaz, V., & Strati, K. (2019). Regulating cellular plasticity to persist: A way for tumor viruses to triumph. Current Opinion in Virology, 39, 1–7. https://doi.org/10.1016/j.coviro.2019.06.007
Young, A. P., Nagarajan, R., & Longmore, G. D. (2003). Mechanisms of transcriptional regulation by Rb–E2F segregate by biological pathway. Oncogene, 22(46), 7209–7217. https://doi.org/10.1038/sj.onc.1206804
Zhang, A., Wang, J., Zheng, B., Fang, X., Angström, T., Liu, C., et al. (2004). Telomere attrition predominantly occurs in precursor lesions during in vivo carcinogenic process of the uterine cervix. Oncogene, 23(44), 7441–7447. https://doi.org/10.1038/sj.onc.1207527
Zheng, Z. M., & Baker, C. C. (2006). Papillomavirus genome structure, expression, and post-transcriptional regulation. Frontiers in Bioscience: A Journal and Virtual Library, 11, 2286–2302. https://doi.org/10.2741/1971
Zheng, X. H., Liang, P. H., Guo, J. X., Zheng, Y. R., Han, J., Yu, L. L., Zhou, Y. G., & Li, L. (2010). Expression and clinical implications of homeobox gene Six1 in cervical cancer cell lines and cervical epithelial tissues. International Journal of Gynecological Cancer, 20(9), 1587–1592
Zhou, H., Blevins, M. A., Hsu, J. Y., Kong, D., Galbraith, M. D., Goodspeed, A., et al. (2020). Identification of a small-molecule inhibitor that disrupts the SIX1/EYA2 Complex, EMT, and metastasis. Cancer Research, 80(12), 2689–2702. https://doi.org/10.1158/0008-5472.CAN-20-0435
Ziegert, C., Wentzensen, N., Vinokurova, S., Kisseljov, F., Einenkel, J., Hoeckel, M., & von Knebel, D. M. (2003). A comprehensive analysis of HPV integration loci in anogenital lesions combining transcript and genome-based amplification techniques. Oncogene, 22, 3977–3984. https://doi.org/10.1038/sj.onc.1206629
Zouridis, A., Kalampokas, T., Panoulis, K., Salakos, N., & Deligeoroglou, E. (2018). Intrauterine HPV transmission: A systematic review of the literature. Archives of Gynecology and Obstetrics, 298, 35–44. https://doi.org/10.1007/s00404-018-4787-4
Zyzak, L. L., MacDonald, L. M., Batova, A., Forand, R., Creek, K. E., & Pirisi, L. (1994). Increased levels and constitutive tyrosine phosphorylation of the epidermal growth factor receptor contribute to autonomous growth of human papillomavirus type 16 immortalized human keratinocytes. Cell Growth & Differentiation: The Molecular Biology Journal of the American Association for Cancer Research, 5(5), 537–547
Funding
This paper was made possible in part by Grant 1R21CA201853 from the National Institutes of Health, National Cancer Institute, USA to LP.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest.
Rights and permissions
About this article
Cite this article
Abboodi, F., Delva, N.C., Emmel, J. et al. Human papillomavirus-mediated carcinogenesis and tumor progression. GENOME INSTAB. DIS. 2, 71–91 (2021). https://doi.org/10.1007/s42764-021-00038-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42764-021-00038-x