Cervical cancer pathophysiology
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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] Aida Javanbakht, M.D.
Overview
It is established that human papillomavirus (HPV) is central to the development of cervical neoplasia, only high risk strain of HPV can cause cervical cancer among women whom are affected. This is mainly because of HPV produced proteins E7 which alters epithelium of cervix mainly at junctional zone.
Pathophysiology
Pathogenesis:
Role of high risk strains of HPV, mainly HPV types 16 and 18 had been identified as a potent cause of cancer of cervix, but there are other cofactors that cause progression of cervical neoplasia, some of these include:[1]
- HLA type
- Immunosuppression
- Sex steroid hormons
- Smoking
Role of HPV in pathogenesis of cervical cancer includes:[2]
Cell growth is regulated largely by two cellular proteins, the tumor suppressor protein, p53, and the retinoblastoma gene product, pRB. Unlike in many other cancers, the p53 in cervical cancer is usually wild type and is not mutated (116). The HPV E6 gene product binds to p53 and targets it for rapid degradation via a cellular ubiquitin ligase (116). This degradation has the same effect as an inactivating mutation (116). As a consequence, the normal activities of p53 which govern G1 arrest, apoptosis, and DNA repair are abrogated. Low-risk HPV E6 proteins do not bind p53 at detectable levels and have no effect on p53 stability in vitro.
Since HPVs encode only 8 to 10 proteins, they must employ host cell factors to regulate viral transcription and replication. HPV replication begins with host cell factors which interact with the LCR region of the HPV genome and begin transcription of the viral E6 and E7 genes. The E6 and E7 gene products deregulate the host cell growth cycle by binding and inactivating tumor suppressor proteins, cell cyclins, and cyclin-dependent kinases
- Human papillomaviruses, a sexually transmitted virus, subtypes 16 and 18 (High risk) play an important role in the pathogenesis of cervical cancer. Once HPV enters an epithelial cell, begins to make the proteins.
- HPV has two major viral oncogenes, E6 proteins bind p53 and causes its degradation, E7 proteins bind and inactivate the Rb protein.
Genetic:
- L-1β, encoded by the IL-1B gene, is an inflammatory cytokine and part of the innate immune system.[3]
- TNF-α, encoded by the TNFA gene, is another potent pro-inflammatory cytokine that has been implicated in the control of HPV infection.
- Polymorphisms within HLA plays a role in pathogenesis of cervical neoplasia.
- Interleukin-12 A and B gene (IL12A and IL12B)
- IFN-γ, encoded by the IFNG gene has defensive role against viruses and induces immune mediated inflammatory responses
- Interleukin-10 and the risk and the progression of cervical cancer have been associated with increased IL-10 serum levels
- Cytotoxic T-lymphocyte antigen-4
- HPV E6/E7 oncogenes, proteins that interfere with cell cycle growth and tumor supressor genes.
- Primary microRNA-218 (pri-miR-218) and laminin-5 β3 (LAMB3)
Associated Conditions:
Gross Pathology:
Microscopic pathology
- Prominent nucleoli.
- Blurred or scalloped epithelial-stromal interface.
- Loss of nuclear polarity.
- Pseudoglandular pattern because of acantholysis and central necrosis.
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Uterus: Cervical Carcinoma: Gross, an excellent example of tumor (labeled as invasive)
Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology -
Histopathologic image (H&E stain) of cervical intraepithelial neoplasia.
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Video
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References
- ↑ Arends MJ, Buckley CH, Wells M (February 1998). "Aetiology, pathogenesis, and pathology of cervical neoplasia". J. Clin. Pathol. 51 (2): 96–103. PMID 9602680.
- ↑ Burd EM (January 2003). "Human papillomavirus and cervical cancer". Clin. Microbiol. Rev. 16 (1): 1–17. PMC 145302. PMID 12525422.
- ↑ . doi:10.1016/S1674-8301(11)60020-1. Check
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