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Cervical Cancer

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Biomarkers and Biosensors for Cervical Cancer Diagnosis

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Abstract

Cervical cancer ranks fourth among all types of cancers in women and accounts for close to 0.6 million new cases worldwide every year. Due to improvements in screening techniques, the mortality rate associated with cervical cancer has fallen by around 50% worldwide. While cervical cancer is the leading cause of death among women in Africa, India and China attribute close to one-third of the total cases reported globally. Epidemiological studies suggest that the human papillomavirus (HPV) is the primary cause of cervical cancer. HPV is also responsible for anal, penile, vaginal, head, and neck cancers. HPV infection is very common that the risk of infection for women in the age of 15–80 years is 50–80%. Most of the HPV infections is cleared by the body inherently. In 10–20% of women, the virus persists and progresses into cervical intraepithelial neoplasm lesions by infecting the basal layer of keratinocytes. The infection metastasizes into an invasive cancer of the cervix upon expression of viral proteins E6, E7, which deregulate cell differentiation and proliferation. The HPV is the primary causative agent for cervical cancer and thus understanding the molecular biology and pathogenesis mechanism of the virus is discussed in this chapter.

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References

  1. Wang JH, Sheppard VB, Schwartz MD, Liang W, Mandelblatt JS (2008) Disparities in cervical cancer screening between Asian American and non-Hispanic white women. Cancer Epidemiol Prev Biomarkers 17:1968–1973

    Article  Google Scholar 

  2. Murphy N, Ring M, Heffron C, King B, Killalea AG, Hughes C, Martin CM, McGuinness E, Sheils O, O’leary JJ (2005) p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer. J Clin Pathol 58:525–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Holmes RS, Hawes SE, Touré P, Dem A, Feng Q, Weiss NS, Kiviat NB (2009) HIV infection as a risk factor for cervical cancer and cervical intraepithelial neoplasia in Senegal. Cancer Epidemiol Prev Biomarkers 18:2442–2446

    Article  CAS  Google Scholar 

  4. Dasari S, Wudayagiri R, Valluru L (2015) Cervical cancer: biomarkers for diagnosis and treatment. Clin Chim Acta 445:7–11

    Article  CAS  PubMed  Google Scholar 

  5. Horner M-J, Altekruse SF, Zou Z, Wideroff L, Katki HA, Stinchcomb DG (2011) US geographic distribution of prevaccine era cervical cancer screening, incidence, stage, and mortality. Cancer Epidemiol Prev Biomarkers 20:591–599

    Article  Google Scholar 

  6. Hemminki K, Chen B (2006) Familial risks for cervical tumors in full and half siblings: etiologic apportioning. Cancer Epidemiol Prev Biomarkers 15:1413–1414

    Article  Google Scholar 

  7. Marlow LAV, Waller J, Wardle J (2009) The impact of human papillomavirus information on perceived risk of cervical cancer. Cancer Epidemiol Prev Biomarkers 18:373–376

    Article  Google Scholar 

  8. Banerjee S, Karunagaran D (2019) An integrated approach for mining precise RNA-based cervical cancer staging biomarkers. Gene 712:143961

    Article  CAS  PubMed  Google Scholar 

  9. Boulet GAV, Horvath CAJ, Berghmans S, Bogers J (2008) Human papillomavirus in cervical cancer screening: important role as biomarker. Cancer Epidemiol Prev Biomarkers 17:810–817

    Article  CAS  Google Scholar 

  10. Tornesello ML, Buonaguro L, Giorgi-Rossi P, Buonaguro FM (2013) Viral and cellular biomarkers in the diagnosis of cervical intraepithelial neoplasia and cancer. Biomed Res Int 2013

    Google Scholar 

  11. Ohgaki H, Kleihues P (2005) Epidemiology and etiology of gliomas. Acta Neuropathol 109:93–108

    Article  PubMed  Google Scholar 

  12. Warwick GP, Harington JS (1973) Some aspects of the epidemiology and etiology of esophageal cancer with particular emphasis on the Transkei, South Africa. In: Advances in cancer research, vol 17. Elsevier, Amsterdam, pp 81–229

    Google Scholar 

  13. Gordis L, Gold EB (1993) Epidemiology and etiology of pancreatic cancer. Pancreas Biol. Pathobiol. Dis. Raven, New York, pp 837–855

    Google Scholar 

  14. Castellsagué X (2008) Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol 110:S4–S7

    Article  PubMed  Google Scholar 

  15. Bosch FX, Qiao Y-L, Castellsagué X (2006) CHAPTER 2 the epidemiology of human papillomavirus infection and its association with cervical cancer. Int J Gynecol Obstet 94:S8–S21

    Article  Google Scholar 

  16. Johansson SL, Cohen SM (1997) Epidemiology and etiology of bladder cancer. Proc Seminars Surg Oncol 13:291–298

    Article  CAS  Google Scholar 

  17. Bosch FX, de Sanjosé S (2007) The epidemiology of human papillomavirus infection and cervical cancer. Dis Markers 23:213–227

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cohen SM, Shirai T, Steineck G (2000) Epidemiology and etiology of premalignant and malignant urothelial changes. Scand J Urol Nephrol 34:105–115

    Article  Google Scholar 

  19. Haverkos HW (2005) Multifactorial etiology of cervical cancer: a hypothesis. Medscape Gen Med 7:57

    Google Scholar 

  20. Schiffman M, Wentzensen N (2013) Human papillomavirus infection and the multistage carcinogenesis of cervical cancer. Cancer Epidemiol Prev Biomarkers 22(4):553–560

    Article  Google Scholar 

  21. Franco EL (1991) The sexually transmitted disease model for cervical cancer: incoherent epidemiologic findings and the role of misclassification of human papillomavirus infection. Epidemiology 2:98–106

    Article  CAS  PubMed  Google Scholar 

  22. Shanta V, Krishnamurthi S, Gajalakshmi CK, Swaminathan R, Ravichandran K (2000) Epidemiology of cancer of the cervix: global and national perspective. J Indian Med Assoc 98:49

    CAS  PubMed  Google Scholar 

  23. Munoz N, Bosch X, Kaldor JM (1988) Does human papillomavirus cause cervical cancer? The state of the epidemiological evidence. Br J Cancer 57:1–5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ansink AC, Heintz APM (1993) Epidemiology and etiology of squamous cell carcinoma of the vulva. Eur J Obstet Gynecol 48:111–115

    Article  CAS  Google Scholar 

  25. Reeves WC, Rawls WE, Brinton LA (1989) Epidemiology of genital papillomaviruses and cervical cancer. Rev Infect Dis 11:426–439

    Article  CAS  PubMed  Google Scholar 

  26. Brinton LA (1992) Epidemiology of cervical cancer--overview. IARC Sci Publ:3–23

    Google Scholar 

  27. Binnie WH (1976) A perspective of oral cancer: epidemiology and etiology of oral cancer in Britain. SAGE Publications, Thousand Oaks

    Book  Google Scholar 

  28. Rubin SC (2001) Cervical cancer: successes and failures. CA Cancer J Clin 51:89–91

    Article  CAS  PubMed  Google Scholar 

  29. Wirdefeldt K, Adami H-O, Cole P, Trichopoulos D, Mandel J (2011) Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol 26:1

    Article  Google Scholar 

  30. Roman A, Munger K (2013) The papillomavirus E7 proteins. Virology 445:138–168. https://doi.org/10.1016/j.virol.2013.04.013

    Article  CAS  PubMed  Google Scholar 

  31. Egawa K (2003) Do human papillomaviruses target epidermal stem cells? Dermatology 207:251–254. https://doi.org/10.1159/000073085

    Article  PubMed  Google Scholar 

  32. Schäfer G, Blumenthal MJ, Katz AA (2015) Interaction of human tumor viruses with host cell surface receptors and cell entry. Viruses 7:2592–2617. https://doi.org/10.3390/v7052592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Knipe DM, Howley P (2013) Fields virology, 6th edn. Wolters Kluwer/Lippincott Williams & Wilkins Health, Philadelphia, PA; ISBN 9781451105636

    Google Scholar 

  34. Kroupis C, Vourlidis N (2011) Human papilloma virus (HPV) molecular diagnostics. Clin Chem Lab Med 49:1783–1799. https://doi.org/10.1515/CCLM.2011.685

    Article  CAS  PubMed  Google Scholar 

  35. Bergvall M, Melendy T, Archambault J (2013) The E1 proteins. Virology 445:35–56. https://doi.org/10.1016/j.virol.2013.07.020

    Article  CAS  PubMed  Google Scholar 

  36. Mcbride AA (2013) The papillomavirus E2 proteins. Virology 445:57–79. https://doi.org/10.1016/j.virol.2013.06.006

    Article  CAS  PubMed  Google Scholar 

  37. Lim DA, Gossen M, Lehman CW, Botchan MR (1998) Competition for DNA binding sites between the short and long forms of E2 dimers underlies repression in bovine papillomavirus type 1 DNA replication control. J Virol 72:1931–1940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bernard BA, Bailly C, Lenoir MC, Darmon M, Thierry F, Yaniv M (1989) The human papillomavirus type 18 (HPV18) E2 gene product is a repressor of the HPV18 regulatory region in human keratinocytes. J Virol 63:4317 LP–4314324

    Article  Google Scholar 

  39. Doorbar J (2013) The E4 protein; structure, function and patterns of expression. Virology 445:80–98. https://doi.org/10.1016/j.virol.2013.07.008

    Article  CAS  PubMed  Google Scholar 

  40. DiMaio D, Petti LM (2013) The E5 proteins. Virology 445:99–114. https://doi.org/10.1016/j.virol.2013.05.006

    Article  CAS  PubMed  Google Scholar 

  41. Vande Pol SB, Klingelhutz AJ (2013) Papillomavirus E6 oncoproteins. Virology 445:115–137. https://doi.org/10.1016/j.virol.2013.04.026

    Article  CAS  PubMed  Google Scholar 

  42. Klug A, Finch JT (1965) Structure of viruses of the papilloma-polyoma type: I. human wart virus. J Mol Biol 11:403–IN44. https://doi.org/10.1016/S0022-2836(65)80066-3

    Article  CAS  PubMed  Google Scholar 

  43. Broniarczyk J, Massimi P, Bergant M, Banks L (2015) Human papillomavirus infectious entry and trafficking is a rapid process. J Virol 89:8727–8732. https://doi.org/10.1128/JVI.00722-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Maglennon GA, McIntosh P, Doorbar J (2011) Persistence of viral DNA in the epithelial basal layer suggests a model for papillomavirus latency following immune regression. Virology 414:153–163. https://doi.org/10.1016/j.virol.2011.03.019

    Article  CAS  PubMed  Google Scholar 

  45. Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA (2012) The biology and life-cycle of human papillomaviruses. Vaccine 30:F55–F70. https://doi.org/10.1016/j.vaccine.2012.06.083

    Article  CAS  PubMed  Google Scholar 

  46. Conway MJ, Meyers C (2009) Replication and assembly of human papillomaviruses. J Dent Res 88:307–317. https://doi.org/10.1177/0022034509333446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fehrmann F, Laimins LA (2003) Human papillomaviruses: targeting differentiating epithelial cells for malignant transformation. Oncogene 22:5201–5207. https://doi.org/10.1038/sj.onc.1206554

    Article  CAS  PubMed  Google Scholar 

  48. Tadlaoui KA, Hassou N, Bennani B, Ennaji MM (2019) Emergence of oncogenic high-risk human papillomavirus types and cervical cancer. Elsevier Inc., Amsterdam; ISBN 9780128194003

    Google Scholar 

  49. Muñoz N, Bosch FX, De Sanjosé S, Herrero R, Castellsagué X, Shah KV, Snijders PJF, Meijer CJLM (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527. https://doi.org/10.1056/NEJMoa021641

    Article  PubMed  Google Scholar 

  50. Infections génitales à HPV (2006) Bases fondamentales. In: Infections à papillomavirus: État des connaissances, pratiques et prévention vaccinale. Springer, Paris, pp 3–45. ISBN 978-2-287-33480-1

    Google Scholar 

  51. Plummer M, Schiffman M, Castle PE, Maucort-Boulch D, Wheeler CM (2007) A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis 195:1582–1589. https://doi.org/10.1086/516784

    Article  PubMed  Google Scholar 

  52. Peter M, Rosty C, Couturier J, Radvanyi F, Teshima H, Sastre-Garau X (2006) MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors. Oncogene 25:5985–5993. https://doi.org/10.1038/sj.onc.1209625

    Article  CAS  PubMed  Google Scholar 

  53. Arias-Pulido H, Peyton CL, Joste NE, Vargas H, Wheeler CM (2006) Human papillomavirus type 16 integration in cervical carcinoma in situ and in invasive cervical cancer. J Clin Microbiol 44:1755–1762. https://doi.org/10.1128/JCM.44.5.1755-1762.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Münger K, Howley PM (2002) Human papillomavirus immortalization and transformation functions. Virus Res 89:213–228. https://doi.org/10.1016/s0168-1702(02)00190-9

    Article  PubMed  Google Scholar 

  55. Burd EM (2003) Human papillomavirus and cervical cancer. Clin Microbiol Rev 16:1–17. https://doi.org/10.1128/CMR.16.1.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are grateful to the Ministry of Human Resource Development, Government of India for the financial support through Scheme for Promotion of Academic and Research Collaboration (SPARC) project “SPARC/2018-2019/P402/SL.” We also acknowledge the support received from the National Research Foundation (NRF) of Korea for the Basic Science Research Program funded by the Ministry of Education (NRF-2019R1A6A1A03033215). We are grateful to SASTRA Deemed University, India and SKKU, South Korea for providing infrastructural support.

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Authors and Affiliations

  1. Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University (SKKU), Suwon, South Korea

    Shrute Kannappan

  2. Research Center for Advanced Materials Technology, Sungkyunkwan University (SKKU), Suwon, South Korea

    Shrute Kannappan

  3. School of Advanced Materials Science and Engineering, Research Center for Advanced Materials Technology, Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon, Republic of Korea

    Jung Heon Lee

  4. School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon, South Korea

    Jung Heon Lee

  5. Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon, South Korea

    Jung Heon Lee

  6. Centre for Nanotechnology and Advanced Biomaterials (CeNTAB), School of Electrical and Electronics Engineering, SASTRA Deemed University, Thanjavur, Tamil Nadu, India

    Muthaiyan Lakshmanakumar & John Bosco Balaguru Rayappan

  7. Centre for Nanotechnology and Advanced Biomaterials (CeNTAB), SASTRA Deemed University, Thanjavur, Tamil Nadu, India

    Noel Nesakumar

  8. School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India

    Noel Nesakumar

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  1. Shrute Kannappan
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  2. Jung Heon Lee
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  3. Muthaiyan Lakshmanakumar
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  4. Noel Nesakumar
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  5. John Bosco Balaguru Rayappan
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Correspondence to John Bosco Balaguru Rayappan .

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Editors and Affiliations

  1. Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), School of Electrical and Electronics Engineering, SASTRA Deemed University, Thanjavur, Tamil Nadu, India

    John Bosco Balaguru Rayappan

  2. School of Advanced Materials Science and Engineering, Research Center for Advanced Materials Technology, Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon, Korea (Republic of)

    Jung Heon Lee

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Kannappan, S., Lee, J.H., Lakshmanakumar, M., Nesakumar, N., Rayappan, J.B.B. (2021). Cervical Cancer. In: Rayappan, J.B.B., Lee, J.H. (eds) Biomarkers and Biosensors for Cervical Cancer Diagnosis. Springer, Singapore. https://doi.org/10.1007/978-981-16-2586-2_2

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