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Recent advances in the study of HPV-associated carcinogenesis

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Virologica Sinica

Abstract

Human papillomaviruses (HPVs) cause virtually all cervical cancers, the second leading cause of death by cancer among women, as well as other anogenital cancers and a subset of head and neck cancers. Approximately half of women, who develop cervical cancer die from it. Despite the optimism that has accompanied the introduction of prophylactic vaccines to prevent some HPV infections, the relatively modest uptake of the vaccine, especially in the developing world, and the very high fraction of men and women who are already infected, means that HPV-associated disease will remain as a significant public health problem for decades. In this review, we summarize some recent findings on HPV-associated carcinogenesis, such as miRNAs in HPV-associated cancers, implication of stem cells in the biology and therapy of HPV-positive cancers, HPV vaccines, targeted therapy of cervical cancer, and drug treatment for HPV-induced intraepithelial neoplasias.

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References

  • Au Yeung CL, Tsang TY, Yau PL, Kwok TT. 2011. Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway. Oncogene, 30: 2401–2410.

    Article  CAS  PubMed  Google Scholar 

  • Bartel DP. 2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116: 281–297.

    Article  CAS  PubMed  Google Scholar 

  • Boccardo E, Noya F, Broker TR, Chow LT, Villa LL. 2004. HPV-18 confers resistance to TNF-alpha in organotypic cultures of human keratinocytes. Virology, 328: 233–243.

    Article  CAS  PubMed  Google Scholar 

  • Bravo IG, Félez-Sánchez M. 2015. Papillomaviruses: Viral evolution, cancer and evolutionary medicine. Evol Med Public Health, 2015: 32–51.

    Article  PubMed Central  PubMed  Google Scholar 

  • Brehm A, Nielsen SJ, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T. 1999. The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBO J, 18: 2449–2458.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bueno MJ, Gómez de Cedrón M, Laresgoiti U, Fernández-Piqueras J, Zubiaga AM, Malumbres M. 2010. Multiple E2F-induced microRNAs prevent replicative stress in response to mitogenic signaling. Mol Cell Biol, 30: 2983–2995.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Collart MA, Panasenko OO. 2012. The Ccr4—not complex. Gene, 492: 42–53.

    Article  CAS  PubMed  Google Scholar 

  • Daayana S, Elkord E, Winters U, Pawlita M, Roden R, Stern PL, Kitchener HC. 2010. Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia. Br J Cancer, 102:1129–1136.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Del Priore G, Gudipudi DK, Montemarano N, Restivo AM, Malanowska-Stega J, Arslan AA. 2010. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol Oncol, 116:464–467.

    Article  PubMed  Google Scholar 

  • Dobson SR, McNeil S, Dionne M, Dawar M, Ogilvie G, Krajden M, Sauvageau C, Scheifele DW, Kollmann TR, Halperin SA, Langley JM, Bettinger JA, Singer J, Money D, Miller D, Naus M, Marra F, Young E. 2013. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA, 309: 1793–1802.

    Article  CAS  PubMed  Google Scholar 

  • Duensing S, Lee LY, Duensing A, Basile J, Piboonniyom S, Gonzalez S, Crum CP, Munger K. 2000. The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc Natl Acad Sci U S A, 97: 10002–10007.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Garnett TO, Filippova M, Duerksen-Hughes PJ. 2006. Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis. Cell Death Differ, 13: 1915–1926.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Georgakilas AG, Tsantoulis P, Kotsinas A, Michalopoulos I, Townsend P, Gorgoulis VG. 2014. Are common fragile sites merely structural domains or highly organized “functional” units susceptible to oncogenic stress? Cell Mol Life Sci, 71: 4519–4544.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Grimm C, Polterauer S, Natter C, Rahhal J, Hefler L, Tempfer CB, Heinze G, Stary G, Reinthaller A, Speiser P. 2012. Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstet Gynecol, 120:152–159.

    Article  CAS  PubMed  Google Scholar 

  • Gu W, Yeo E, McMillan N, Yu C. 2011. Silencing oncogene expression in cervical cancer stem-like cells inhibits their cell growth and self-renewal ability. Cancer Gene Ther, 18: 897–905.

    Article  CAS  PubMed  Google Scholar 

  • Hibbitts S. 2010. TA-CIN, a vaccine incorporating a recombinant HPV fusion protein (HPV16 L2E6E7) for the potential treatment of HPV16-associated genital diseases. Curr Opin Mol Ther, 12: 598–606.

    CAS  PubMed  Google Scholar 

  • Howie HL, Katzenellenbogen RA, Galloway DA. 2009. Papillomavirus E6 proteins. Virology, 384: 324–334.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Huh KW, DeMasi J, Ogawa H, Nakatani Y, Howley PM, Münger K. 2005. Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600. Proc Natl Acad Sci U S A, 102: 11492–11497.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ji J, Wei X, Wang Y. 2014. Embryonic stem cell markers Sox-2 and OCT4 expression and their correlation with WNT signal pathway in cervical squamous cell carcinoma. Int J Clin Exp Pathol, 7: 2470–2476.

    PubMed Central  PubMed  Google Scholar 

  • Klingelhutz AJ, Foster SA, McDougall JK. 1996. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature, 380: 79–82.

    Article  CAS  PubMed  Google Scholar 

  • Lajer CB, Garnæs E, Friis-Hansen L, Norrild B, Therkildsen MH, Glud M, Rossing M, Lajer H, Svane D, Skotte L, Specht L, Buchwald C, Nielsen FC. 2012. The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer. Br J Cancer, 106: 1526–1534.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lewis BP, Burge CB, Bartel DP. 2005. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120: 15–20.

    Article  CAS  PubMed  Google Scholar 

  • Li B, Hu Y, Ye F, Li Y, Lv W, Xie X. 2010. Reduced miR-34a expression in normal cervical tissues and cervical lesions with high-risk human papillomavirus infection. Int J Gynecol Cancer, 20: 597–604.

    Article  PubMed  Google Scholar 

  • Liu HC, Chen GG, Vlantis AC, Tse GM, Chan AT, van Hasselt CA. 2008. Inhibition of apoptosis in human laryngeal cancer cells by E6 and E7 oncoproteins of human papillomavirus 16. J Cell Biochem, 103:1125–1143.

    Article  CAS  PubMed  Google Scholar 

  • Longworth MS, Laimins LA. 2004. The binding of histone deacetylases and the integrity of zinc finger-like motifs of the E7 protein are essential for the life cycle of human papillomavirus type 31. J Virol, 78:3533–3541.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lopez J, Poitevin A, Mendoza-Martinez V, Perez-Plasencia C, Garcia-Carranca A. 2012. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance. BMC Cancer, 12:48.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McLaughlin-Drubin ME, Munger K. 2009. Oncogenic activities of human papillomaviruses. Virus Res, 143: 195–208.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Michael S, Lambert PF, Strati K. 2013. The HPV16 oncogenes cause aberrant stem cell mobilization. Virology, 443: 218–225.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mirghani H, Amen F, Moreau F, Lacau St, Guily J. 2015. Do highrisk human papillomaviruses cause oral cavity squamous cell carcinoma?. Oral Oncol, 51: 229–236.

    Article  CAS  PubMed  Google Scholar 

  • Monk BJ, Mas Lopez L, Zarba JJ, Oaknin A, Tarpin C, Termrungruanglert W, Alber JA, Ding J, Stutts MW, Pandite LN. 2010. Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer. J Clin Oncol, 28: 3562–3569.

    Article  CAS  PubMed  Google Scholar 

  • Moody CA, Laimins LA. 2010. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer, 10:550–560.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen CL, Münger K. 2008. Direct association of the HPV16 E7 oncoprotein with cyclin A/CDK2 and cyclin E/CDK2 complexes. Virology, 380: 21–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ. 2000. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem, 275: 6764–6769.

    Article  CAS  PubMed  Google Scholar 

  • Pim D, Bergant M, Boon SS, Ganti K, Kranjec C, Massimi P, Subbaiah VK, Thomas M, Tomaić V, Banks L. 2012. Human papillomaviruses and the specificity of PDZ domain targeting. FEBS J, 279: 3530–3537.

    Article  CAS  PubMed  Google Scholar 

  • Romanowski B, Schwarz TF, Ferguson LM, Ferguson M, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Behre U, Suryakiran P, Thomas F, Struyf F. 2014. Immune response to the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose or 3-dose schedule up to 4 years after vaccination: results from a randomized study. Hum Vaccin Immunother, 10: 1155–1165.

    Article  PubMed  Google Scholar 

  • Ronco LV, Karpova AY, Vidal M, Howley PM. 1998. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev, 12: 2061–2072.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. 1993. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell, 75: 495–505.

    Article  CAS  PubMed  Google Scholar 

  • Schiller JT, Lowy DR. 2012. Understanding and learning from the success of prophylactic human papillomavirus vaccines. Nat Rev Microbiol, 10: 681–692.

    Article  CAS  PubMed  Google Scholar 

  • Serrano B, Alemany L, Tous S, Bruni L, Clifford GM, Weiss T, Bosch FX, de Sanjosé S. 2012. Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease. Infect Agent Cancer, 7:38.

    Article  PubMed Central  PubMed  Google Scholar 

  • Tang AL, Owen JH, Hauff SJ, Park JJ, Papagerakis S, Bradford CR, Carey TE, Prince ME. 2013. Head and neck cancer stem cells: the effect of HPV—an in vitro and mouse study. Otolaryngol Head Neck Surg, 149: 252–260.

    Article  PubMed Central  PubMed  Google Scholar 

  • Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. 2014. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med, 370: 734–743.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • The Cancer Genome Atlas Network (TCGA). 2015. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature, 517: 576–582.

    Article  Google Scholar 

  • Thomas MC, Chiang CM. 2005. E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation. Mol Cell, 17: 251–264.

    Article  CAS  PubMed  Google Scholar 

  • Tran NP, Hung CF, Roden R, Wu TC. 2014. Control of HPV infection and related cancer through vaccination. Recent Results Cancer Res, 193: 149–171.

    Article  PubMed  Google Scholar 

  • Underbrink MP, Howie HL, Bedard KM, Koop JI, Galloway DA. 2008. E6 proteins from multiple human betapapillomavirus types degrade Bak and protect keratinocytes from apoptosis after UVB irradiation. J Virol, 82: 10408–10417.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Van Pachterbeke C, Bucella D, Rozenberg S, Manigart Y, Gilles C, Larsimont D, Vanden Houte K, Reynders M, Snoeck R, Bossens M. 2009. Topical treatment of CIN 2+ by cidofovir: results of a phase II, double-blind, prospective, placebo-controlled study. Gynecol Oncol, 115: 69–74.

    Article  PubMed  Google Scholar 

  • Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N. 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 189: 12–19.

    Article  CAS  PubMed  Google Scholar 

  • Wang JW, Jagu S, Wang C, Kitchener HC, Daayana S, Stern PL, Pang S, Day PM, Huh WK, Roden RB. 2014a. Measurement of neutralizing serum antibodies of patients vaccinated with human papillomavirus L1 or L2-based immunogens using furin-cleaved HPV Pseudovirions. PLoS One, 9: e101576.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wang X, Wang HK, Li Y, Hafner M, Banerjee NS, Tang S, Briskin D, Meyers C, Chow LT, Xie X, Tuschl T, Zheng ZM. 2014b. microRNAs are biomarkers of oncogenic human papillomavirus infections. Proc Natl Acad Sci U S A, 111: 4262–4267.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang X, Wang HK, McCoy JP, Banerjee NS, Rader JS, Broker TR, Meyers C, Chow LT, Zheng ZM. 2009. Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6. RNA, 15: 637–647.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • White EA, Kramer RE, Tan MJ, Hayes SD, Harper JW, Howley PM. 2012a. Comprehensive analysis of host cellular interactions with human papillomavirus E6 proteins identifies new E6 binding partners and reflects viral diversity. J Virol, 86: 13174–13186.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • White EA, Sowa ME, Tan MJ, Jeudy S, Hayes SD, Santha S, Münger K, Harper JW, Howley PM. 2012b. Systematic identification of interactions between host cell proteins and E7 oncoproteins from diverse human papillomaviruses. Proc Natl Acad Sci U S A, 109: 260–267.

    Article  Google Scholar 

  • Wright JD, Viviano D, Powell MA, Gibb RK, Mutch DG, Grigsby PW, Rader JS. 2006. Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer. Gynecol Oncol, 103: 489–93.

    Article  CAS  PubMed  Google Scholar 

  • Xu M, Katzenellenbogen RA, Grandori C, Galloway DA. 2013. An unbiased in vivo screen reveals multiple transcription factors that control HPV E6-regulated hTERT in keratinocytes. Virology, 446: 17–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ye F, Zhou C, Cheng Q, Shen J, Chen H. 2008. Stem-cell-abundant proteins Nanog, Nucle ostemin and Musashi1 are highly expressed in malignant cervical epithelial cells. BMC Cancer, 8: 108–112.

    Article  PubMed Central  PubMed  Google Scholar 

  • Zheng ZM, Wang X. 2011. Regulation of cellular miRNA expression by human papillomaviruses. Biochim Biophys Acta, 1809: 668–677.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • zur Hausen H. 2009. Papillomaviruses in the causation of human cancers — a brief historical account. Virology, 384: 260–265.

    Article  PubMed  Google Scholar 

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Correspondence to Zhi-Xiang Xu.

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Jin, L., Xu, ZX. Recent advances in the study of HPV-associated carcinogenesis. Virol. Sin. 30, 101–106 (2015). https://doi.org/10.1007/s12250-015-3586-3

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