Pathophysiology
Summary
The cervix is anatomically characterized by an internal os, connecting to the uterus, and an external os, opening into the vagina. Two key regions, the endocervix and exocervix, are lined by mucus-secreting columnar cells and stratified squamous cells, respectively. The endocervix is prone to developing benign growths that can cause vaginal bleeding known as endocervical polyps, commonly found in middle-aged women with a history of multiple pregnancies
The squamo-columnar junction is the transformation zone is where the endocervical columnar cells transition into exocervical squamous cells. In this area, the columnar cells often undergo benign squamous metaplasia, triggered by the acidic vaginal environment, maintained at a pH of 3.8-4.5 by lactobacilli.
Cervical dysplasia & cancer is primarily caused by high-risk strains HPV strains (16 & 18). These strains disrupt cellular regulation by inhibiting p53 and Rb tumor suppressor genes, both crucial for the G1 to S phase transition in the cell cycle. The integration of high-risk HPV strains into host DNA leads to overexpression of oncogenes E6 and E7, further inhibiting p53 and Rb respectively. These high-risk of HPV strains show an affinity for the immature metaplastic squamous cells in the transformation zone, manifesting as koilocytosis, characterized by perinuclear vacuolization within squamous cells on histology.
Cervical intraepithelial neoplasia (CIN) originates from the basal epithelial cells and is categorized into three classes: CIN 1, which presents as mild dysplasia affecting the lower one-third of the epithelium; CIN 2, moderate dysplasia involving the lower two-thirds; and CIN 3, severe dysplasia involving more than two-thirds or the full thickness of the epithelium. These classes are also known as LSIL (low-grade squamous intraepithelial lesion) and HSIL (high-grade squamous intraepithelial lesion) for CIN 1 and CIN 2/3, respectively. While CIN 1 often resolves spontaneously in young, healthy women, CIN 2 and CIN 3 carry a higher risk of progressing to cervical cancer, notably through invasion of the basement membrane.
Screening for cervical dysplasia and cancer is commonly performed using a Pap smear, which is vital for sampling the transformation zone. If abnormal cells are detected, follow-up procedures like colposcopy and biopsies are carried out. During colposcopy, acetic acid is applied to the cervix, turning abnormal areas white and facilitating biopsy of these regions.
The most frequent type of cervical cancer is squamous cell carcinoma, distinguishable histologically by the presence of keratin pearls & intercellular bridges. This form of cancer typically spreads down and out, potentially leading to compression of the ureters and resultant postrenal kidney injury. Clinical presentation often includes postcoital bleeding. Preventive measures include the HPV vaccine, which provides immunity against common HPV strains.
Lesson Outline
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FAQs
The endocervix is the inner part of the cervix that lines the cervical canal, leading to the internal os, which opens into the uterus. It is lined by mucus-secreting columnar cells. On the other hand, the exocervix is the outer part of the cervix that is exposed to the vagina and leads to the external os, which opens into the vagina. The exocervix is lined by stratified squamous cells. These two regions meet at the squamo-columnar junction, also known as the ‘transformation zone.’
Endocervical polyps are benign growths originating from the endocervix. They are lined by mucus-secreting columnar cells, similar to the normal endocervical lining. These polyps are most commonly found in middle-aged women who have a history of multiple pregnancies. The primary symptom associated with endocervical polyps is vaginal bleeding, although some women may not experience any symptoms.
High-risk strains of HPV, such as HPV 16 and 18, pose a significant risk to cervical health by causing cervical dysplasia and potentially leading to cervical cancer. These strains inhibit the function of tumor suppressor genes p53 and Rb, leading to uncontrolled cellular replication. The high-risk HPV strains can also integrate into the host DNA, causing overexpression of oncogenes E6 and E7, which further inhibit p53 and Rb, respectively.
The Pap smear is a screening test for cervical dysplasia and cancer. During the test, a swab of the cervix is taken, with particular attention to sampling the transformation zone where abnormal cells are most likely to be found. If abnormal cells are detected, a colposcopy is usually performed for further evaluation. During colposcopy, acetic acid is applied to the cervix to highlight abnormal areas, which are then biopsied for further examination and diagnosis.
Low-grade squamous intraepithelial lesions (LSIL), also known as CIN1, involve mild dysplasia affecting the lower one-third of the epithelium. These lesions often resolve spontaneously in young, healthy women and are less likely to progress to cervical cancer. On the other hand, high-grade squamous intraepithelial lesions (HSIL), or CIN2/3, involve moderate to severe dysplasia affecting more than two-thirds of the epithelium. These lesions have a higher risk of progressing to cervical cancer and require more aggressive monitoring and treatment.
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