Cervix Pathology PDF

# CERVIX ## I. BASIC PRINCIPLES - Anatomically, comprises the "neck" of the uterus - Divided into the exocervix (visible on vaginal exam) and endocervix - Exocervix is lined by nonkeratinizing squamous epithelium. - Endocervix is lined by a single layer of columnar cells. - Junction bet...

# CERVIX ## I. BASIC PRINCIPLES - Anatomically, comprises the "neck" of the uterus - Divided into the exocervix (visible on vaginal exam) and endocervix - Exocervix is lined by nonkeratinizing squamous epithelium. - Endocervix is lined by a single layer of columnar cells. - Junction between the exocervix and endocervix is called the transformation zone. ## II. HPV - Sexually transmitted DNA virus that infects the lower genital tract, especially the cervix in the transformation zone - Infection is usually eradicated by acute inflammation; persistent infection leads to an increased risk for cervical dysplasia (cervical intraepithelial neoplasia, CIN). - Risk of CIN depends on HPV type, which is determined by DNA sequencing. - High-risk-HPV types 16, 18, 31, and 33 - Low-risk-HPV types 6 and 11 - High-risk HPV produce E6 and E7 proteins which result in increased destruction of p53 and Rb, respectively. Loss of these tumor suppressor proteins increases the risk for CIN. ## III. CERVICAL INTRAEPITHELIAL NEOPLASIA - Characterized by koilocytic change, disordered cellular maturation, nuclear atypia, and increased mitotic activity within the cervical epithelium. - Divided into grades based on the extent of epithelial involvement by immature dysplastic cells - CIN I involves < 1/3 of the thickness of the epithelium. - CIN II involves < 2/3 of the thickness of the epithelium. - CIN III involves slightly less than the entire thickness of the epithelium. - Carcinoma in situ (CIS) involves the entire thickness of the epithelium. - CIN classically progresses in a stepwise fashion through CIN I, CIN II, CIN III, and CIS to become invasive squamous cell carcinoma. - Progression is not inevitable (e.g., CIN I often regresses). - The higher the grade of dysplasia, the more likely it is to progress to carcinoma and the less likely it is to regress to normal. ## IV. CERVICAL CARCINOMA - Invasive carcinoma that arises from the cervical epithelium - Most commonly seen in middle-aged women (average age is 40-50 years) - Presents as vaginal bleeding, especially postcoital bleeding, or cervical discharge - Key risk factor is high-risk HPV infection; secondary risk factors include smoking and immunodeficiency (e.g., cervical carcinoma is an AIDS-defining illness). - Most common subtypes of cervical carcinoma are squamous cell carcinoma (80% of cases) and adenocarcinoma (15% of cases). Both types are related to HPV infection. - Advanced tumors often invade through the anterior uterine wall into the bladder, blocking the ureters. Hydronephrosis with postrenal failure is a common cause of death in advanced cervical carcinoma. ## V. SCREENING AND PREVENTION OF CERVICAL CARCINOMA - The goal of screening is to catch dysplasia (CIN) before it develops into carcinoma. - Progression from CIN to carcinoma, on average, takes 10-20 years. - Screening begins at age 21 and is initially performed every three years. - Pap smear is the gold standard for screening. - Cells are scraped from the transformation zone using a brush and analyzed under a microscope. - Dysplastic cells are classified as low grade (CIN I) or high grade (CIN II and III). - High-grade dysplasia is characterized by cells with hyperchromatic (dark) nuclei and high nuclear to cytoplasmic ratios. - Pap smear is the most successful screening test developed to date. - It is responsible for a significant reduction in the morbidity and mortality of cervical carcinoma. - Women who develop invasive cervical carcinoma usually have not undergone screening. - An abnormal Pap smear is followed by confirmatory colposcopy (visualization of cervix with a magnifying glass) and biopsy. - Limitations of the Pap smear include inadequate sampling of the transformation zone (false negative screening) and limited efficacy in screening for adenocarcinoma. - Despite Pap smear screening, the incidence of adenocarcinoma has not decreased significantly. - Immunization is effective in preventing HPV infections. - The quadrivalent vaccine covers HPV types 6, 11, 16, and 18. - Antibodies generated against types 6 and 11 protect against condylomas. - Antibodies generated against types 16 and 18 protect against CIN and carcinoma. - Pap smears are still necessary due to the limited number of HPV types covered by the vaccine.