From the Guidelines
Cervical cancer originates from the epithelial tissue of the cervix, specifically from the transformation zone where the columnar epithelium of the endocervix meets the squamous epithelium of the ectocervix, with the primary pathophysiology involving persistent infection with high-risk human papillomavirus (HPV), particularly types 16 and 18, which account for approximately 70% of cases, as supported by the most recent guidelines 1.
Tissue of Origin
The tissue of origin of cervical cancer is the epithelial tissue of the cervix. This includes the transformation zone where the columnar epithelium of the endocervix meets the squamous epithelium of the ectocervix.
Pathophysiology
The primary pathophysiology of cervical cancer involves persistent infection with high-risk human papillomavirus (HPV). HPV types 16 and 18 are the most common high-risk types, accounting for approximately 70% of cases. HPV infects the basal cells of the cervical epithelium through microabrasions, and viral oncoproteins E6 and E7 interfere with tumor suppressor proteins p53 and retinoblastoma protein (pRb), leading to uncontrolled cell proliferation.
Progression to Cancer
This process typically progresses slowly through precancerous stages called cervical intraepithelial neoplasia (CIN), graded as CIN 1 (mild dysplasia), CIN 2 (moderate dysplasia), and CIN 3 (severe dysplasia/carcinoma in situ), before potentially developing into invasive cervical cancer.
Risk Factors
Risk factors that contribute to progression include smoking, immunosuppression, long-term oral contraceptive use, multiple sexual partners, and early sexual debut.
Prevention
Prevention focuses on HPV vaccination before sexual debut and regular cervical screening through Pap smears or HPV testing to detect precancerous changes before they progress to cancer, as recommended by recent guidelines 1.
Key points to consider:
- The most recent guidelines support the use of HPV vaccination and regular cervical screening for the prevention of cervical cancer 1.
- High-risk HPV types, particularly types 16 and 18, are responsible for approximately 70% of cervical cancer cases 1.
- Persistent infection with high-risk HPV is necessary for the development of cervical cancer and its precursor lesions 1.
From the Research
Tissue of Origin
- The tissue of origin of cervical cancer is the epithelial cells of the cervix, specifically the cervical transformation zone (TZ) where the squamous epithelium meets the columnar epithelium of the endocervix 2, 3.
- The cervical transformation zone is a narrow region of metaplastic squamous epithelium that develops at the squamocolumnar junction between the ectocervix and endocervix 2.
- The cervix has a complex epithelial organisation, comprising the stratified epithelium of the ectocervix, the columnar epithelium of the endocervix, and the cervical transformation zone (TZ) 3.
Pathophysiology
- Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HPV) types, especially HPV type 16 (HPV-16) and HPV-18 4, 5, 6.
- HPV infection disrupts normal cell-cycle control and promotes uncontrolled cell division, leading to the accumulation of genetic damage 5, 6.
- The high-risk E6 and E7 proteins of HPV drive cell proliferation through their association with PDZ domain proteins and Rb (retinoblastoma), and contribute to neoplastic progression 6.
- E6-mediated p53 degradation prevents the normal repair of chance mutations in the cellular genome, leading to the development of cancer 6.
- Most cervical cancers arise in individuals who fail to resolve their HPV infection and who retain oncogene expression for years or decades 6.