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Biochemistry (Moscow)

, Volume 84, Issue 7, pp 782–799 | Cite as

Carcinogenesis Associated with Human Papillomavirus Infection. Mechanisms and Potential for Immunotherapy

  • M. Vonsky
  • M. Shabaeva
  • A. Runov
  • N. Lebedeva
  • S. Chowdhury
  • J. M. Palefsky
  • M. IsaguliantsEmail author
Review

Abstract

Human papillomavirus (HPV) infection is responsible for approximately 5% of all cancers and is associated with 30% of all pathogen-related cancers. Cervical cancer is the third most common cancer in women worldwide; about 70% of cervical cancer cases are caused by the high-risk HPVs (HR HPVs) of genotypes 16 and 18. HPV infection occurs mainly through sexual contact; however, viral transmission via horizontal and vertical pathways is also possible. After HPV infection of basal keratinocytes or ecto-endocervical transition zone cells, viral DNA persists in the episomal form. In most cases, infected cells are eliminated by the immune system. Occasionally, elimination fails, and HPV infection becomes chronic. Replication of HPVs in dividing epithelial cells is accompanied by increased expression of the E6 and E7 oncoproteins. These oncoproteins are responsible for genomic instability, disruption of the cell cycle, cell proliferation, immortalization, and malignant transformation of HPV-infected cells. Besides, E6 and E7 oncoproteins induce immunosuppression, preventing the detection of HPV-infected and transformed cells by the immune system. HPV integration into the genome of the host cell leads to the upregulation of E6 and E7 expression and contributes to HPV-associated malignization. Prophylactic HPV vaccines can prevent over 80% of HPV-associated anogenital cancers. The vaccine elicits immune response that prevents initial infection with a given HPV type but does not eliminate persistent virus once infection has occurred and does not prevent development of the HPV-associated neoplasias, which necessitates the development of therapeutic vaccines to treat chronic HPV infections and HPV-associated malignancies.

Keywords

human papillomavirus (HPV) squamous cell carcinoma carcinogenesis cervical cancer intraepithelial neoplasias epidemiology E6 and E7 oncoproteins 

Abbreviations

AIDS

acquired immunodeficiency syndrome

CIN1, CIN2, and CIN3

light, moderate, and severe cervical intraepithelial neoplasia, respectively

HAART

highly active antiretroviral therapy

(HR) HPV

(high carcinogenic risk) human papillomavirus

HSIL and LSIL

high- and low-grade squamous intraepithelial lesion, respectively

L1 and L2

large and small capsid proteins of HPV, respectively

LCR, NCR, and URR

long control region, noncoding region, and upstream regulatory region of HPV genome, respectively

ORF

open reading frame

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References

  1. 1.
    Shope, R. E., and Hurst, E. W. (1933) Infectious papillo-matosis of rabbits, with a note on histopathology, J. Exp. Med., 58, 607–624.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., and Jemal, A. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J. Clin., 68, 394–424, doi: 10.3322/caac.21492.CrossRefPubMedGoogle Scholar
  3. 3.
    Arbyn, M., Xu, L., Simoens, C., and Martin-Hirsch, P. P. (2018) Prophylactic vaccination against human papillo-maviruses to prevent cervical cancer and its precursors, Cochrane Database Syst. Rev., 5, CD009069, doi: 10.1002/14651858.CD009069.pub3.PubMedGoogle Scholar
  4. 4.
    Osazuwa-Peters, N., Massa, S. T., Simpson, M. C., Adjei Boakye, E., and Varvares, M. A. (2018) Survival of human papillomavirus-associated cancers: filling in the gaps, Cancer, 124, 18–20, doi: 10.1002/cncr.30945.CrossRefPubMedGoogle Scholar
  5. 5.
    McBride, A. A. (2017) Mechanisms and strategies of papil-lomavirus replication, Biol. Chem., 398, 919–927, doi: 10.1515/hsz-2017-0113.CrossRefPubMedGoogle Scholar
  6. 6.
    IARC (2007) Human papillomaviruses, IARC Monogr. Eval. Carcinog. Risks Hum., 90, 1–636.Google Scholar
  7. 7.
    Khallouf, H., Grabowska, A. K., and Riemer, A. B. (2014) Therapeutic vaccine strategies against human papillomavirus, Vaccines, 2, 422–462, doi: 10.3390/vaccines2020422.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Solomon, D., Davey, D., Kurman, R., Moriarty, A., O’Connor, D., Prey, M., Raab, S., Sherman, M., Wilbur, D., Wright, T., Jr., and Young, N. (2018) The 2001 Bethesda System: terminology for reporting results of cervical cytology, JAMA, 287, 2114–2119, doi: 10.1001/jama.287.16.2114.CrossRefGoogle Scholar
  9. 9.
    Araldi, R., Sant’Ana, T. A., Modolo, D. G., de Melo, T. C., Spadacci-Morena, D. D., de Cassia Stocco, R., Cerutti, J. M., and de Souza, E. B. (2018) The human papillomavirus (HPV)-related cancer biology: an overview, Biomed. Pharmacother., 106, 1537–1556, doi: 10.1016/j.biopha.2018.06.149.CrossRefPubMedGoogle Scholar
  10. 10.
    De Vincenzo, R., Ricci, C., Conte, C., and Scambia, G. (2013) HPV vaccine cross-protection: highlights on additional clinical benefit, Gynecol. Oncol., 130, 642–651, doi: 10.1016/j.ygyno.2013.05.033.CrossRefPubMedGoogle Scholar
  11. 11.
    Bruni, L., Albero, G., Serrano, B., Mena, M., Gomez, D., Munoz, J., Bosch, F. X., and de Sanjose, S. (2019) Human Papillomavirus and Related Diseases in the World. Summary Report 22 January 2019, ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre).Google Scholar
  12. 12.
    Wang, C. J., Sparano, J., and Palefsky, J. M. (2017) Human immunodeficiency virus/AIDS, human papillomavirus, and anal cancer, Surg. Oncol. Clin. N. Am., 26, 17–31, doi: 10.1016/j.soc.2016.07.010.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chesson, H. W., Dunne, E. F., Hariri, S., and Markowitz, L. E. (2014) The estimated lifetime probability of acquiring human papillomavirus in the United States, Sex. Transm. Dis., 41, 660–664, doi: 10.1097/OLQ.0000000000000193.CrossRefPubMedGoogle Scholar
  14. 14.
    Heitmann, E., and Harper, D. (2012) Prophylactic HPV vaccines and the prevention of cervical intraepithelial neoplasia, Cur. Obstet. Gynecol. Rep., 1, 95–105, doi: 10.1007/s13669-012-0017-4.CrossRefGoogle Scholar
  15. 15.
    Husain, R. S., and Ramakrishnan, V. (2015) Global variation of human papillomavirus genotypes and selected genes involved in cervical malignancies, An. Glob. Health, 81, 675–683, doi: 10.1016/j.aogh.2015.08.026.CrossRefGoogle Scholar
  16. 16.
    Mbulawa, Z. Z. A., van Schalkwyk, C., Hu, N. C., Meiring, T. L., Barnabas, S., Dabee, S., Jaspan, H., Kriek, J. M., Jaumdally, S. Z., Muller, E., Bekker, L. G., Lewis, D. A., Dietrich, J., Gray, G., Passmore, J. S., and Williamson, A. L. (2018) High human papillomavirus (HPV) prevalence in South African adolescents and young women encourages expanded HPV vaccination campaigns, PLoS One, 13, e0190166, doi: 10.1371/journal.pone.0190166.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Nweke, M. C., Okolo, C. A., Daous, Y., and Esan, O. A. (2018) Challenges of human papillomavirus infection and associated diseases in low-resource countries, Arch. Pathol. Lab. Med., 142, 696–699, doi: 10.5858/arpa.2017-0565-RA.CrossRefPubMedGoogle Scholar
  18. 18.
    Clifford, G. M., Tully, S., and Franceschi, S. (2017) Carcinogenicity of human papillomavirus (HPV) types in HIV-positive women: a meta-analysis from HPV infection to cervical cancer, Clin. Infect. Dis., 64, 1228–1235, doi: 10.1093/cid/cix135.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lopukhov, P. D. (2018) Scientific and Methodological Substantiation for Optimization of Epidemiological Surveillance and Prevention of Human Papillomavirus Infection: Candidate’s dissertation in Medicine [in Russian], Moscow.Google Scholar
  20. 20.
    Petrova, G. V., Gretsova, O. P., Shahzadova, A. O., Prostov, M. Yu., Prostov, Yu. I., and Samsonov, Yu. V. (2018) in Malignant Tumors in Russia in 2017. Incidence and Mortality (Kaprin, A. D., Starinsky, V. V., and Petrova, G. V., eds.) [in Russian], P. A. Hertsen Moscow Oncology Research Center, Moscow, pp. 4–130.Google Scholar
  21. 21.
    Rogovskaya, S. I., Miheeva, I. V., Shipulina, O. Yu., Minkina, G. N., Podzolkova, N. M., Radzinsky, V. E., and Shipulin, G. A. (2012) Prevalence of papillomavirus infection in Russia, Epidemiol. Vaktsinoprof., 1, 25–33.Google Scholar
  22. 22.
    Kasihina, E. I. (2011) Papillomavirus infection today: clinical diversity, treatment, and prevention, Lechashchii Vrach, 10, 6–8.Google Scholar
  23. 23.
    Depuydt, C. E., Beert, J., Bosmans, E., and Salembier, G. (2016) Human papillomavirus (HPV) virion induced cancer and subfertility, two sides of the same coin, Facts Views Vis. Obgyn., 8, 211–222.PubMedGoogle Scholar
  24. 24.
    Lee, B., Lee, S. W., and Kim, D. I. (2017) HPV prevalence in the foreskins of asymptomatic healthy infants and children: systematic review and meta-analysis, Sci. Rep., 7, 7050, doi: 10.1038/s41598-017-07506-z.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Rintala, M. A., Grenman, S. E., Puranen, M. H., Isolauri, E., Ekblad, U., Kero, P. O., and Syrjanen, S. M. (2005) Transmission of high-risk human papillomavirus (HPV) between parents and infant: a prospective study of HPV in families in Finland, J. Clin. Microbiol., 43, 376–381, doi: 10.1128/JCM.43.1.376-381.2005.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Smith, E. M., Parker, M. A., Rubenstein, L. M., Haugen, T. H., Hamsikova, E., and Turek, L. P. (2010) Evidence for vertical transmission of HPV from mothers to infants, Infect. Dis. Obstet. Gynecol., 2010, 326389, doi: 10.1155/2010/326369.CrossRefGoogle Scholar
  27. 27.
    Sarkola, M., Rintala, M., Grenman, S., and Syrjanen, S. (2008) Human papillomavirus DNA detected in breast milk, Pediatr. Infect. Dis. J., 27, 557–558, doi: 10.1097/INF.0b013e318169ef47.CrossRefPubMedGoogle Scholar
  28. 28.
    Teixeira, L. O., Amaral, S. C., Finger-Jardim, F., da Hora, V. P., Goncalves, C. V., Soares, M. A., and de Martinez, A. M. B. (2015) Frequencia do papilomavirus humano na placenta, no colostro e no sangue do cordao umbilical, Rev. Bras. Ginecol. Obstet., 37, 203–207, doi: 10.1590/SO100-720320150005293.CrossRefPubMedGoogle Scholar
  29. 29.
    Green, G. E., Bauman, N. M., and Smith, R. J. (2000) Pathogenesis and treatment of juvenile onset recurrent respiratory papillomatosis, Otolaryngol. Clin. North. Am., 33, 187–207.CrossRefPubMedGoogle Scholar
  30. 30.
    Liu, Z., Tasnuva, R., and Nyitray, A. (2015) Penises not required: a systematic review of the potential for human papillomavirus horizontal transmission that is non-sexual or does not include penile penetration, Sex. Health, 13, 10–21, doi: 10.1071/SH15089.CrossRefGoogle Scholar
  31. 31.
    Zarochentseva, V., Belaya, Yu. M., Samsigina, G. A., Scherbakova, M. Yu., Vizhlova, E. N., and Malinovskaya, V. V. (2017) Papillomavirus infection and HPV-associated diseases, Lechashchii Vrach, 4, 56–63.Google Scholar
  32. 32.
    Castellsague, X., Drudis, T., Canadas, M. P., Gonce, A., Ros, R., Perez, J. M., Quintana, M. J., Munoz, J., Albero, G., de Sanjose, S., and Bosch, F. X. (2009) Human papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain, BMC Infect. Dis., 9, 74, doi: 10.1186/1471-2334-9-74.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Palefsky, J. M. (1998) Human papillomavirus infection and anogenital neoplasia in human immunodeficiency virus-positive men and women, J. Natl. Cancer Inst. Monogr., 23, 15–20.CrossRefGoogle Scholar
  34. 34.
    Rassohin, V. V., Leonova, O. N., Panteleeva, O. V., Smirnova, N. L., Fomenkova, N. V., Zagdin, Z. M., and Belyakov, N. A. (2012) Incidence and character of oncological diseases in HIV patients with and without highly active antiretroviral therapy, VICh-Infektsiya Immunosupressii, 4, 34–43.Google Scholar
  35. 35.
    Palefsky, J. M., Holly, E. A., Ralston, M. L., Da Costa, M., and Greenblatt, R. M. (2001) Prevalence and risk factors for anal HPV infection in HIV-positive and high-risk HIV-negative women, J. Infect. Dis., 183, 383–391, doi: 10.1086/318071.CrossRefPubMedGoogle Scholar
  36. 36.
    Frisch, M., Biggar, R. J., and Goedert, J. J. (2000) Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immuno-deficiency syndrome, J. Natl. Cancer Inst., 92, 1500–1510.CrossRefPubMedGoogle Scholar
  37. 37.
    Palefsky, J. M. (2017) Human papillomavirus-associated anal and cervical cancers in HIV-infected individuals: incidence and prevention in the antiretroviral therapy era, Curr. Opin. HIV AIDS, 12, 26–30, doi: 10.1097/COH.0000000000000336.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Adler, D. H., Kakinami, L., Modisenyane, T., Tshabangu, N., Mohapi, L., De Bruyn, G., Martinson, N. A., and Omar, T. (2012) Increased regression and decreased incidence of human papillomavirus-related cervical lesions among HIV-infected women on HAART, AIDS, 26, 1645–1652, doi: 10.1097/QAD.0b013e32835536a3.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Palefsky, J. M., and Holly, E. A. (2003) Immunosuppression and co-infection with HIV-1, J. Natl. Cancer Inst. Monogr., 31, 41–46, doi: 10.1093/oxfordjournals.jncimonographs.a003481.CrossRefGoogle Scholar
  40. 40.
    Ghebre, R. G., Grover, S., Xu, M. J., Chuang, L. T., and Simonds, H. (2017) Cervical cancer control in HIV-infected women: past, present and future, Gynecol. Oncol. Rep., 21, 101–108, doi: 10.1016/j.gore.2017.07.009.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Paramsothy, P., Jamieson, D. J., and Heilig, C. M. (2009) The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology, Obstet. Gynecol., 113, 26–31, doi: 10.1097/AOG.0b013e31819225cb.CrossRefPubMedGoogle Scholar
  42. 42.
    Kelly, H., Weiss, H. A., Benavente, Y., de Sanjose, S., Mayaud, P., ART and HPV Review Group (2018) Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis, Lancet. HIV, 5, e45–e58, doi: 10.1016/S2352-3018(17)30149-2.CrossRefPubMedGoogle Scholar
  43. 43.
    Harden, M. E., and Munger, K. (2017) Human papillo-mavirus molecular biology, Mutat. Res. Rev. Mutat. Res., 772, 3–12, doi: 10.1016/j.mrrev.2016.07.002.CrossRefPubMedGoogle Scholar
  44. 44.
    Buck, C., Day, P., and Trus, B. (2013) The papillomavirus major capsid protein L1, Virology, 445, 169–174, doi: 10.1016/j.virol.2013.05.038.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ustav, M., Ustav, E., Szymanski, P., and Stenlund, A. (1991) Identification of the origin of replication of bovine papillomavirus and characterization of the viral origin recognition factor E1, EMBO J., 10, 4321–4329.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Ferraro, C., Canedo, M., Oliveira, S., Carvalho, M., and Dias, E. (2011) Infeccao oral pelo HPV e lesoes epiteliais proliferativas associadas, J. Bras. Patol. Med. Lab., 47, 451–459.CrossRefGoogle Scholar
  47. 47.
    Wallace, N. A., and Galloway, D. A. (2014) Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses, Semin. Cancer Biol., 26, 30–42, doi: 10.1016/j.semcancer.2013.12.003.CrossRefPubMedGoogle Scholar
  48. 48.
    Schuck, S., and Stenlund, A. A. (2015) Conserved regulatory module at the C-terminus of the papillomavirus E1 helicase domain controls E1 helicase assembly, J. Virol., 89, 1129–1142, doi: 10.1128/JVI.01903-14.CrossRefPubMedGoogle Scholar
  49. 49.
    Helfer, C. M., Yan, J., and You, J. (2014) The cellular bromodomain protein Brd4 has multiple functions in E2-mediated papillomavirus transcription activation, Viruses, 6, 3228–3249, doi: 10.3390/v6083228.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Doorbar, J. (2017) Host control of human papillomavirus infection and disease, Best Pract. Res. Clin. Obstet. Gynaecol., 47, 27–41, doi: 10.1016/j.bpobgyn.2017.08.001.CrossRefPubMedGoogle Scholar
  51. 51.
    Hoppe-Seyler, K., Bossler, F., and Braun, J. A. (2018) Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchor-age-independent growth through activation of STAT3 and AKT pathways, Cell Death Dis., 9, 1055, doi: 10.1038/s41419-018-1059-y.CrossRefGoogle Scholar
  52. 52.
    Muller, M., Prescott, E. L., Wasson, C. W., and Macdonald, A. (2015) Human papillomavirus E5 oncoprotein: function and potential target for antiviral therapeutics, Future Virol., 10, 27–39, doi: 10.2217/fvl.14.99.CrossRefGoogle Scholar
  53. 53.
    Wetherill, L. F., Holmes, K. K., Verow, M., Muller, M., Howell, G., Harris, M., Fishwick, C., Stonehouse, N., Foster, R., Blair, G. E., Griffin, S., and Macdonald, A. (2012) High-risk human papillomavirus E5 oncoprotein displays channel-forming activity sensitive to small-molecule inhibitors, J. Virol., 86, 5341–5351, doi: 10.1128/JVI.06243-11.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    DiMaio, D., and Petti, L. M. (2013) The E5 proteins, Virology, 445, 99–114, doi: 10.1016/j.virol.2013.05.006.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Kivi, N., Greco, D., Auvinen, P., and Auvinen, E. (2008) Genes involved in cell adhesion, cell motility and mitogenic signaling are altered due to HPV 16 E5 protein expression, Oncogene, 27, 2532–2541, doi: 10.1038/sj.onc.1210916.CrossRefPubMedGoogle Scholar
  56. 56.
    Venuti, A., Paolini, F., Nasir, L., Corteggio, A., Roperto, S., Campo, M. S., and Borzacchiello, G. (2011) Papillomavirus E5: the smallest oncoprotein with many functions, Mol. Cancer, 10, 140, doi: 10.1186/1476-4598-10-140.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Vonsky, M. S., Runov, A. L., Gordeychuk, I. V., and Isaguliants, M. G. (2019) Therapeutic vaccines against human papilloma viruses. Achievements and prospects, Biochemistry (Moscow), 84, 800–816.Google Scholar
  58. 58.
    Hengstermann, A., Linares, L. K., Ciechanover, A., Whitaker, N. J., and Scheffner, M. (2001) Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells, Proc. Natl. Acad. Sci. USA, 98, 1218–1223, doi: 10.1073/pnas.98.3.1218.CrossRefPubMedGoogle Scholar
  59. 59.
    Tomaic, V. (2016) Functional roles of E6 and E7 oncoproteins in HPV-induced malignancies at diverse anatomical sites, Cancers (Basel), 8, E95, doi: 10.3390/cancers8100095.Google Scholar
  60. 60.
    Boon, S. S., Tomaic, V., Thomas, M., Roberts, S., and Banks, L. (2015) Cancer-causing human papillomavirus E6 proteins display major differences in the phospho-regulation of their PDZ interactions, J. Virol., 89, 1579–1586, doi: 10.1128/JVI.01961-14.CrossRefPubMedGoogle Scholar
  61. 61.
    Songock, W. K., Kim, S. M., and Bodily, J. M. (2017) The human papillomavirus E7 oncoprotein as a regulator of transcription, Virus Res., 231, 56–75, doi: 10.1016/j.virus-res.2016.10.017.CrossRefPubMedGoogle Scholar
  62. 62.
    Katzenellenbogen, R. (2017) Telomerase induction in HPV infection and oncogenesis, Viruses, 9, E180, doi: 10.3390/v9070180.CrossRefPubMedGoogle Scholar
  63. 63.
    Song, S., Pitot, H. C., and Lambert, P. F. (1999) The human papillomavirus type 16 E6 gene alone is sufficient to induce carcinomas in transgenic animals, J. Virol., 73, 5887–5893.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Dyson, N. J. (2016) RB1: a prototype tumor suppressor and an enigma, Genes Dev., 30, 1492–502, doi: 10.1101/gad. 282145.116.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Godinho, S. A., and Pellman, D. (2014) Causes and consequences of centrosome abnormalities in cancer, Philos. Trans. R. Soc. Lond. B. Biol. Sci., 369, 20130467, doi: 10.1098/rstb.2013.0467.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Sen, P., Ganguly, P., and Ganguly, N. (2017) Modulation of DNA methylation by human papillomavirus E6 and E7 oncoproteins in cervical cancer, Oncol. Lett., 15, 11–22, doi: 10.3892/ol.2017.7292.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Mirabello, L., Yeager, M., Yu, K., Clifford, G. M., Xiao, Y., Zhu, B., Cullen, M., Boland, J. F., Wentzensen, N., Nelson, C. W., Raine-Bennett, T., Chen, Z., Bass, S., Song, L., Yang, Q., Steinberg, M., Burdett, L., Dean, M., Roberson, D., Mitchell, J., Lorey, T., Franceschi, S., Castle, P. E., Walker, J., Zuna, R., Kreimer, A. R., Beachler, D. C., Hildesheim, A., Gonzalez, P., Porras, C., Burk, R. D., and Schiffman, M. (2017) HPV16 E7 genetic conservation is critical to carcinogenesis, Cell, 170, 1164–1174, doi: 10.1016/j.cell.2017.08.001.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Yu, J. H., Shi, W. W., Zhou, M. Y., Liu, J. M., Han, Q. Y., and Xu, H. H. (2019) Genetic variability and oncogenic risk association of human papillomavirus type 58 E6 and E7 genes in Taizhou area, China, Gene, 686, 171–176, doi: 10.1016/j.gene.2018.11.066.CrossRefPubMedGoogle Scholar
  69. 69.
    Chabeda, A., Yanez, R., Jr., Lamprecht, R., Meyers, A. E., Rybicki, E. P., and Hitzeroth, I. I. (2017) Therapeutic vaccines for high-risk HPV-associated diseases, Papillomavirus Res., 5, 46–58, doi: 10.1016/j.pvr.2017.12.006.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Doorbar, J. (2005) The papillomavirus life cycle, J. Clin. Virol., 32, S7–S15, doi: 10.1016/j.jcv.2004.12.006.CrossRefPubMedGoogle Scholar
  71. 71.
    DiGiuseppe, S., Bienkowska-Haba, M., Guion, L. G., and Sapp, M. (2016) Cruising the cellular highways: how human papillomavirus travels from the surface to the nucleus, Virus Res., 231, 1–9, doi: 10.1016/j.virusres.2016.10.015.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Herfs, M., Soong, T. R., Delvenne, P., and Crum, C. P. (2017) Deciphering the multifactorial susceptibility of mucosal junction cells to HPV infection and related carcinogenesis, Viruses, 9, E85, doi: 10.3390/v9040085.Google Scholar
  73. 73.
    Moody, C., and Laimins, L. (2010) Human papillomavirus oncoproteins: pathways to transformation, Nat. Rev. Cancer, 10, 550–560, doi: 10.1038/nrc2886.CrossRefPubMedGoogle Scholar
  74. 74.
    Stanley, M. A. (2012) Epithelial cell responses to infection with human papillomavirus, Clin. Microbiol. Rev., 25, 215–230, doi: 10.1128/CMR.05028-11.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Munday, J. (2014) Papillomaviruses in felids, Vet. J., 199, 340–347, doi: 10.1016/j.tvjl.2013.11.025.CrossRefPubMedGoogle Scholar
  76. 76.
    Depuydt, C. E., Thys, S., Beert, J., Jonckheere, J., Salembier, G., and Bogers, J. J. (2016) Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer, Int. J. Cancer, 139, 2021–2032, doi: 10.1002/ijc.30238.CrossRefPubMedGoogle Scholar
  77. 77.
    Brossfield, J. E., Chan, P. J., Patton, W. C., and King, A. (1999) Tenacity of exogenous human papillomavirus DNA in sperm washing, J. Assist. Reprod. Genet., 16, 325–328.Google Scholar
  78. 78.
    Depuydt, C. E., Jonckheere, J., Berth, M., Salembier, G. M., Vereecken, A. J., and Bogers, J. J. (2015) Serial type-specific human papillomavirus (HPV) load measurement allows differentiation between regressing cervical lesions and serial virion productive transient infections, Cancer Med., 4, 1294–1302, doi: 10.1002/cam4.473.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Gupta, S., Kumar, P., and Das, B. C. (2018) HPV: molecular pathways and targets, Curr. Probl. Cancer, 42, 161–174, doi: 10.1016/j.currproblcancer.2018.03.003.CrossRefPubMedGoogle Scholar
  80. 80.
    Holmes, A., Lameiras, S., Jeannot, E., Marie, Y., Castera, L., Sastre-Garau, X., and Nicolas, A. (2016) Mechanistic signatures of HPV insertions in cervical carcinomas, NPJ Genom. Med., 1, 16004, doi: 10.1038/npjgenmed.2016.4.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Akagi, K., Li, J., Broutian, T. R., Padilla-Nash, H., Xiao, W., Jiang, B., Rocco, J. W., Teknos, T. N., Kumar, B., Wangsa, D., He, D., Ried, T., Symer, D. E., and Gillison, M. L. (2014) Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability, Genome Res., 24, 185–199, doi: 10.1101/gr.164806.113.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Hu, Z., Zhu, D., Wang, W., Li, W., Jia, W., Zeng, X., Ding, W., Yu, L., Wang, X., Wang, L., Shen, H., Zhang, C., Liu, H., Liu, X., Zhao, Y., Fang, X., Li, S., Chen, W., Tang, T., Fu, A., Wang, Z., Chen, G., Gao, Q., Li, S., Xi, L., Wang, C., Liao, S., Ma, X., Wu, P., Li, K., Wang, S., Zhou, J., Wang, J., Xu, X., Wang, H., and Ma, D. (2015) Genomewide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism, Nat. Genet., 47, 158–163, doi: 10.1038/ng.3178.CrossRefPubMedGoogle Scholar
  83. 83.
    Parfenov, M., Pedamallu, C. S., Gehlenborg, N., Freeman, S. S., Danilova, L., Bristow, C. A., Lee, S., Hadjipanayis, A. G., Ivanova, E. V., Wilkerson, M. D., Protopopov, A., Yang, L., Seth, S., Song, X., Tang, J., Ren, X., Zhang, J., Pantazi, A., Santoso, N., Xu, A. W., Mahadeshwar, H., Wheeler, D. A., Haddad, R. I., Jung, J., Ojesina, A. I., Issaeva, N., Yarbrough, W. G., Hayes, D. N., Grandis, J. R., El-Naggar, A. K., Meyerson, M., Park, P. J., Chin, L., Seidman, J. G., Hammerman, P. S., and Kucherlapati, R. (2014) Characterization of HPV and host genome interactions in primary head and neck cancers, Proc. Natl. Acad. Sci. USA, 111, 15544–15549, doi: 10.1073/pnas.1416074111.CrossRefPubMedGoogle Scholar
  84. 84.
    Groves, I. J., and Coleman, N. (2018) Human papillo-mavirus genome integration in squamous carcinogenesis: what have next-generation sequencing studies taught us? J. Pathol., 245, 9–18, doi: 10.1002/path.5058.CrossRefPubMedGoogle Scholar
  85. 85.
    Oyervides-Munoz, M. A., Perez-Maya, A. A., Rodriguez-Gutierrez, H. F., Gomez-Macias, G. S., Fajardo-Ramirez, O. R., Trevino, V., Barrera-Saldana, H. A., and Garza-Rodriguez, M. L. (2018) Understanding the HPV integration and its progression to cervical cancer, Infect. Genet. Evol., 61, 134–144, doi: 10.1016/j.meegid.2018.03.003.CrossRefPubMedGoogle Scholar
  86. 86.
    Magaldi, T. G., Almstead, L. L., Bellone, S., Prevatt, E. G., Santin, A. D., and DiMaio, D. (2012) Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation, Virology, 422, 114–124, doi: 10.1016/j.virol.2011.10.012.CrossRefPubMedGoogle Scholar
  87. 87.
    Bossler, F., Kuhn, B. J., Gunther, T., Kraemer, S. J., Khalkar, P., Adrian, S., Lohrey, C., Holzer, A., Shimobayashi, M., Durst, M., Mayer, A., Rosl, F., Grundhoff, A., Krijgsveld, J., Hoppe-Seyler, K., and Hoppe-Seyler, F. (2019) Repression of human papillo-mavirus oncogene expression under hypoxia is mediated by PI3K/mTORC2/AKT signaling, MBio, 10, e02323–18, doi: 10.1128/mBio.02323-18.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Johansson, C., Somberg, M., Li, X., Winquist, E., Fay, J., Ryan, F., Pim, D., Banks, L., and Schwartz, S. (2012) HPV-16 E2 contributes to induction of HPV-16 late gene expression by inhibiting early polyadenylation, EMBO J., 31, 3212–3227, doi: 10.1038/emboj.2012.147.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Yang, A., Farmer, E., Wu, T. C., and Hung, C. F. (2016) Perspectives for therapeutic HPV vaccine development, J. Biomed. Sci., 23, 75, doi: 10.1186/s12929-016-0293-9.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Vinokurova, S., Wentzensen, N., Kraus, I., Klaes, R., Driesch, C., Melsheimer, P., Kisseljov, F., Durst, M., Schneider, A., and Doeberitz, M. V. K. (2008) Typedependent integration frequency of human papillomavirus genomes in cervical lesions, Cancer Res., 68, 307–313, doi: 10.1158/0008-5472.CAN-07-2754.CrossRefPubMedGoogle Scholar
  91. 91.
    Roura, E., Travier, N., Waterboer, T., de Sanjose, S., Bosch, F. X., Pawlita, M., Pala, V., Weiderpass, E., Margall, N., Dillner, J., Gram, I. T., Tjonneland, A., Munk, C., Palli, D., Khaw, K. T., Overvad, K., Clavel-Chapelon, F., Mesrine, S., Fournier, A., Fortner, R. T., Ose, J., Steffen, A., Trichopoulou, A., Lagiou, P., Orfanos, P., Masala, G., Tumino, R., Sacerdote, C., Polidoro, S., Mattiello, A., Lund, E., Peeters, P. H., Bueno-de-Mesquita, H. B., Quiros, J. R., Sanchez, M. J., Navarro, C., Barricarte, A., Larranaga, N., Ekstrom, J., Lindquist, D., Idahl, A., Travis, R. C., Merritt, M. A., Gunter, M. J., Rinaldi, S., Tommasino, M., Franceschi, S., Riboli, E., and Castellsague, X. (2016) The influence of hormonal factors on the risk of developing cervical cancer and pre-cancer: results from the EPIC cohort, PLoS One, 11, e0147029, doi: 10.1371/journal.pone.0147029.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Den Boon, J. A., Pyeon, D., Wang, S. S., Horswill, M., Schiffman, M., Sherman, M., Zuna, R. E., Wang, Z., Hewitt, S. M., Pearson, R., Schott, M., Chung, L., He, Q., Lambert, P., Walker, J., Newton, M. A., Wentzensen, N., and Ahlquist, P. (2015) Molecular transitions from papillo-mavirus infection to cervical precancer and cancer: role of stromal estrogen receptor signaling, Proc. Natl. Acad. Sci. USA, 112, E3255–E3264, doi: 10.1073/pnas.1509322112.CrossRefGoogle Scholar
  93. 93.
    Nunes, R. A. L., Morale, M. G., Silva, G. A. F., Villa, L. L., and Termini, L. (2018) Innate immunity and HPV: friends or foes, Clinics (Sao Paulo), 73 (Suppl. 1), e549s, doi: 10.6061/clinics/2018/e549s.Google Scholar
  94. 94.
    Stanley, M. (2010) HPV–immune response to infection and vaccination, Infect. Agent. Cancer, 5, 19, doi: 10.1186/1750-9378-5-19.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Ribeiro-Muller, L., and Muller, M. (2014) Prophylactic papillomavirus vaccines, Clin. Dermatol., 32, 235–347, doi: 10.1016/j.clindermatol.2013.08.008.CrossRefPubMedGoogle Scholar
  96. 96.
    Martinez-Gomez, X., Curran, A., Campins, M., Alemany, L., Rodrigo-Pendas, J., Borruel, N., Castellsague, X., Diaz-de-Heredia, C., Moraga-Llop, F., del Pino, M., and Torne, A. (2019) Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations, Spain, 2016, Euro Surveill., 24, 1700857, doi: 10.2807/1560-7917.ES.2019.24.7.1700857.CrossRefPubMedCentralGoogle Scholar
  97. 97.
    Petrosky, E., Bocchini, J. A., Hariri, S., Chesson, H., Curtis, R., Saraiya, M., Unger, E., Markowitz, L., and Centers for Disease Control and Prevention (CDC) (2015) Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices, MMWR Morb. Mortal. Wkly Rep., 64, 300–304.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Markowitz, L. E., Dunne, E. F., Saraiya, M., Lawson, H. W., Chesson, H., Unger, E. R., Centers for Disease Control and Prevention (CDC), and Advisory Committee on Immunization Practices (ACIP) (2007) Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR Recomm. Rep., 56, 1–24.PubMedGoogle Scholar
  99. 99.
    Lehtinen, M., Lagheden, C., and Luostarinen, T. (2017) Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point registry-based follow-up of three cohorts from randomized trials, BMJ Open, 7, e015867, doi: 10.1136/bmjopen-2017-015867.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Maver, P. J., and Poljak, M. (2018) Progress in prophylactic human papillomavirus (HPV) vaccination in 2016: a literature review, Vaccine 2018, 36, 5416–5423, doi: 10.1016/j.vaccine.2017.07.113.Google Scholar
  101. 101.
    Lehtinen, M., Baussano, I., Paavonen, J., Vanska, S., and Dillner, J. (2019) Eradication of human papillomavirus and elimination of HPV-related diseases–scientific basis for global public health policies, Expert Rev. Vaccines, 18, 153–160, doi: 10.1080/14760584.2019.1568876.CrossRefPubMedGoogle Scholar
  102. 102.
    Klosky, J. L., Gamble, H. L., Spunt, S. L., Randolph, M. E., Green, D. M., and Hudson, M. M. (2009) Human papillomavirus vaccination in survivors of childhood cancer, Cancer, 115, 5627–5636, doi: 10.1002/cncr.24669.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Papasavvas, E., Surrey, L. F., Glencross, D. K., Azzoni, L., Joseph, J., Omar, T., Feldman, M., Williamson, A., Siminya, M., Swarts, A., Yin, X., Liu, Q., Firnhaber, C., and Montanera, L. J. (2016) High-risk oncogenic HPV genotype infection associates with increased immune activation and T cell exhaustion in ART-suppressed HIV-1-infected women, Oncoimmunology, 5, e1128612, doi: 10.1080/2162402X.2015.1128612.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Kostinov, M. P., and Zverev, V. V. (2012) Cost-effectiveness of vaccination against human papillomavirus in the Russian Federation, Zh. Mikrobiol. Epidemiol. Immunobiol., 2, 43–50.Google Scholar
  105. 105.
    Zheng, Z. M., and Baker, C. C. (2006) Papillomavirus genome structure, expression, and post-transcriptional regulation, Front. Biosci., 11, 2286–302.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • M. Vonsky
    • 1
    • 2
  • M. Shabaeva
    • 3
  • A. Runov
    • 1
    • 2
    • 4
  • N. Lebedeva
    • 4
    • 5
  • S. Chowdhury
    • 6
  • J. M. Palefsky
    • 6
  • M. Isaguliants
    • 4
    • 7
    • 8
    • 9
    Email author
  1. 1.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia
  2. 2.Almazov National Medical Research CenterSt. PetersburgRussia
  3. 3.Pavlov First St. Petersburg State Medical UniversitySt. PetersburgRussia
  4. 4.Gamaleya Federal Research Center for Epidemiology and MicrobiologyMoscowRussia
  5. 5.Moscow Regional Center of AIDS and Infectious Diseases Prevention and TreatmentMoscowRussia
  6. 6.University of CaliforniaSan Francisco School of MedicineSan FranciscoUSA
  7. 7.Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological ProductsRussian Academy of SciencesMoscowRussia
  8. 8.Karolinska Institutet, Department of MicrobiologyTumor and Cell BiologyStockholmSweden
  9. 9.Department of PathologyRiga Stradins UniversityRigaLatvia

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