Cervical cancer causes
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Cervical cancer Microchapters |
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Diagnosis |
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Cervical cancer causes On the Web |
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American Roentgen Ray Society Images of Cervical cancer causes |
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Risk calculators and risk factors for Cervical cancer causes |
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Cervical cancer Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Cervical cancer causes On the Web |
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American Roentgen Ray Society Images of Cervical cancer causes |
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Risk calculators and risk factors for Cervical cancer causes |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2], Monalisa Dmello, M.B,B.S., M.D. [3], Daniel Adamec[4]
Overview
Cervical cancer is primarily caused by persistent infection with oncogenic (high risk) Human papillomavirus (HPV). While a necessary etiological factor, the majority of infections are transient and resolve without progressing to malignancy. HPV is transmitted through mucosal and cutaneous contact, most commonly via sexual activity.[1] In 2024, approximately 13,820 new cases and 4,360 related deaths were expected in the United States.[2] Key risk factors for acquiring HPV include early age at first intercourse and a high number of lifetime sexual partners.[3]
Causes
- Human papillomavirus is the main cause of cervical cancer. High-risk HPV types infect the basal layer of the cervical epithelium, particularly at the transformation zone, leading to malignant transformation.[4]
- HPV is a small, non-enveloped, double-stranded circular DNA virus of approximately 8 kb, encoding eight genes, with a virion diameter of approximately 45-55 nm.[5] It is transmitted primarily through skin-to-skin contact, in particular via sexual activity.[6]
- Oncogenic high-risk strains include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.[7]
- The viral oncogenes E6 and E7 interfere with cell cycle control by inactivating the tumor suppressor proteins p53 and pRb, respectively. E6 promotes p53 degradation by recruiting the cellular E3 ubiquitin ligase E6-AP (UBE3A; facilitating ubiquitin-mediated proteasomal degradation), whereas E7 inactivates pRb primarily through direct binding (disrupting E2F, enabling constitutive cell cycle entry).[8] This disruption leads to genomic instability and the abnormal proliferation of squamous and glandular cells. [6]
- Previously the association between HPV infection and glandular type of cervical neoplasia was considered not as strong as that of squamous carcinoma of the cervix. However, current evidence establishes high-risk HPV (particularly HPV 18) as the causative agent in the majority of endocervical adenocarcinomas.[9]
References
- ↑ International Agency for Research on Cancer. (2007). Human papillomaviruses (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 90). Lyon: IARC.
- ↑ Siegel, R. L., Giaquinto, A. N., & Jemal, A. (2024). Cancer statistics, 2024. CA: A Cancer Journal for Clinicians, 74(1), 12–49. https://doi.org/10.3322/caac.21820
- ↑ Kjaer, S. K., Chackerian, B., van den Brule, A. J. C., Svare, E. I., Paull, G., Walbomers, J. M. M., … Meijer, C. J. L. M. (2001). High-risk human papillomavirus is sexually transmitted: Evidence from a follow-up study of virgins starting sexual activity (intercourse). Cancer Epidemiology, Biomarkers & Prevention, 10(2), 101–106.
- ↑ Doorbar, J. (2006). Molecular biology of human papillomavirus infection and cervical cancer. Clinical Science, 110(5), 525–541. https://doi.org/10.1042/CS20050369
- ↑ 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
- ↑ 6.0 6.1 Burd EM (January 2003). "Human papillomavirus and cervical cancer". Clin. Microbiol. Rev. 16 (1): 1–17. PMID 12525422.
- ↑ Muñoz, N., Bosch, F. X., de Sanjosé, S., Herrero, R., Castellsagué, X., Shah, K. V., … Meijer, C. J. L. M. (2003). Epidemiologic classification of human papillomavirus types associated with cervical cancer. New England Journal of Medicine, 348(6), 518–527. https://doi.org/10.1056/NEJMoa021641
- ↑ Huibregtse, J. M., Scheffner, M., & Howley, P. M. (1993). Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. Molecular and Cellular Biology, 13(2), 775–784. https://doi.org/10.1128/mcb.13.2.775
- ↑ Andersson, S., Rylander, E., Larsson, B., Strand, A., Silfverswärd, C., & Wilander, E. (2001). The role of human papillomavirus in cervical adenocarcinoma carcinogenesis. European Journal of Cancer, 37(2), 246–250. https://doi.org/10.1016/S0959-8049(00)00376-6