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 the main cause of development of cervical neoplasia, only high risk strain of HPV can cause cervical cancer among women whom are affected. This is 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][2][3]
- HLA type
- Immunosuppression, since response to HPV infection is cell mediated.
- Use of oral contraceptives had been identified to play an important role in
- Smoking which disrupts immune response.
- History of promiscuous sexual activity in male partner
- Early age sexual activities
- Co-infection with herpse simplex virus type 2, cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and HHV-7, which cause promotion of infection with HPV and plays an initiation role.
Role of HPV in pathogenesis of cervical cancer widely related to dirupting cell cycle growth and regulations, summary of these include:[4]
- The high risk HPV E6 and E7 gene products which are involved in viral replication and oncogenesis bind to p53 and prevents its normal activities which is G1 arrest, apoptosis, and DNA repair.
- HPV enters the host cell which are squamous cells of epithelium in cervix, mainly in junctional zone, between the columnar epithelium of the endocervix and the squamous epithelium of the ectocervix and that is how viral transcription and replication begins.
- HPV infection of the basal layer of epithelium takes place by attachement via different mechanism of entry, this happens by cell surface heparan sulfate, stabilizing protoglycans and Integrin.
Genetic:
- L-1β, encoded by the IL-1B gene, is an inflammatory cytokine and part of the innate immune system.[5][6]
- 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 pathoegensis 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: 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:
Conditions associated with cervical cancer include:
Gross Pathology:
Microscopic pathology
Microscopic morphology of low‐grade squamous intraepithelial lesions (CIN 1) include:[7]
- Presence of koilocytosis (perinuclear cytoplasmic clearing with peripheral condensation of the cytoplasm)
- Irregular nuclear contours, either binucleation or/and multinucleation
- Hyperchromasia and/or cellular pleomorphism
- Mild dysplasia
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High‐grade dysplasia (CIN 2 and 3) is characterized by the following features:
- Loss of maturation
- Nuclear crowding
- Loss of nuclear polarity
- Prominent cytonuclear atypia, increase in nuclear‐to‐cytoplasmic ratios
- Irregular nuclear contours and coarse chromatin.
- Increased proliferation and mitotic changes in the upper part of the epithelium.
- In CIN2, most cytonuclear abnormalities are seen in the lower and middle third of the epithelium.
- CIN3 characteristic features include:
- Full‐thickness cytonuclear atypia
- Minimal to absent maturation
- Numerous mitotic activities
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.
- ↑ zur Hausen H (December 1982). "Human genital cancer: synergism between two virus infections or synergism between a virus infection and initiating events?". Lancet. 2 (8312): 1370–2. PMID 6129466.
- ↑ Vanakankovit N, Taneepanichskul S (January 2008). "Effect of oral contraceptives on risk of cervical cancer". J Med Assoc Thai. 91 (1): 7–12. PMID 18386537.
- ↑ 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
|doi=value (help). Missing or empty|title=(help) - ↑ Shi, Ting-Yan; Chen, Xiao-Jun; Zhu, Mei-Ling; Wang, Meng-Yun; He, Jing; Yu, Ke-Da; Shao, Zhi-Ming; Sun, Meng-Hong; Zhou, Xiao-Yan; Cheng, Xi; Wu, Xiaohua; Wei, Qingyi (2013). "A pri-miR-218variant and risk of cervical carcinoma in Chinese women". BMC Cancer. 13 (1). doi:10.1186/1471-2407-13-19. ISSN 1471-2407.
- ↑ Kalof, A. N; Cooper, K. (2006). "Our approach to squamous intraepithelial lesions of the uterine cervix". Journal of Clinical Pathology. 60 (5): 449–455. doi:10.1136/jcp.2005.036426. ISSN 0021-9746.