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


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.


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



acquired immunodeficiency syndrome

CIN1, CIN2, and CIN3

light, moderate, and severe cervical intraepithelial neoplasia, respectively


highly active antiretroviral therapy


(high carcinogenic risk) human papillomavirus


high- and low-grade squamous intraepithelial lesion, respectively

L1 and L2

large and small capsid proteins of HPV, respectively


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


open reading frame


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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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